Más de 50 hongos comestibles, considerados como alimento en países asiáticos, ofrecen efectos terapéuticos. Aunque todos están desprovistos de toxicidad y son tolerados excelentemente, solo seis han sido ampliamente investigados. Entre ellos destaca el hongo Maitake, que ha demostrado actividad inmunoestimulante de utilidad antineoplásica y antiretroviral, disminuye el colesterol, triglicéridos y niveles elevados de glucosa en pacientes que padecen diabetes tipo adulto y contribuye a controlar la tensión arterial. Su excelente tolerabilidad, beneficios comprobados y compatibilidad con tratamientos con fármacos sintéticos convierten a este hongo en extraordinario complemento a los tratamientos contra diversas condiciones y enfermedades crónicas.
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Introducción
En Japón, las personas se han beneficiado de este gigante hongo comestible por más de 3.000 años, pero solo hasta 1980 se logró identificar sus propiedades terapéuticas. En ese país, es muy apreciado tanto por sus cualidades culinarias como por sus propiedades terapéuticas
Su nombre científico Grifola frondosa se deriva de grifón, una bestia de la mitología griega con cabeza y alas de águila y cuerpo de león, y frondosa, que se refiere a sus hojas. En idioma japonés, mai significa danza y take significa hongo, por lo tanto "hongo danzante". Aparentemente este nombre proviene del aspecto de sus cuerpos frutales que se sobreponen y mueven con el viento.
En tiempos feudales, maitake esa considerado tan valioso que se pagaba su peso en monedas de plata. Incluso actualmente los buscadores del hongo se reservan celosamente la localización de las áreas donde crece. Maitake es muy buscado por chefs por su excelente sabor y textura y por otras personas debido a sus beneficios terapéuticos.
Maitake crece en masas pesadas en la base o raíces de diversos árboles. Su crecimiento óptimo ocurre bajo un rango limitado de temperaturas, humedad y otros factores ambientales. Algunas zonas del noreste japonés son especialmente adecuadas para su crecimiento silvestre. Maitake también puede encontrarse en los bosques del norte de Asia, Europa y el este de los EEUU. Aunque su crecimiento silvestre es relativamente raro el Japón, no es un hongo extraño a los bosques de los EEUU y Canadá, donde se le conoce como "gallina de los bosques" debido a su forma y color que se asemejan a las plumas de esta ave. Solo se encuentra raramente en los bosques occidentales de los EEUU.
El cultivo del Maitake es reciente. Solo en las últimas dos décadas se logró el cambio de Maitake silvestre a cultivos del hongo. El cultivo comercial en Japón se inició en 1981 con 325 toneladas. En el año 2001 la producción comercial de maitake en el ámbito mundial sobrepasa las 40.000 toneladas anuales. |
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Principios activos:
Diversos principios activos con demostrada actividad antineoplásica e inmunomoduladora han sido aislados de más de 30 especies de hongos. Solo unos pocos han pasado a la siguiente fase: evaluación clínica objetiva de su potencial antineoplásico e inmunomodulador en humanos. Muchos de los principios activos micóticos se relacionan químicamente a la estructura ß-D-glucan (es decir, polímeros de d-glucosa con otros monosacáricos) o ß-D-glucanos enlazados a proteínas (llamados péptidos-polisacáridos o proteoglicanes). Por regla general, los proteoglicanes ofrecen mayor actividad inmunoestimulante que la correspondiente a los glucanes libres.
A principios de la década de los ochenta, el micólogo japonés Hiroaki Nanba, de la Universidad Farmacéutica de Kobe llegó a la conclusión que los polisacáridos del maitake tenían un estructura única y demostró que se consumo lograba un pronunciado efecto antitumoral e inmunomodulador, mayor que el de otros hongos medicinales, en modelos animales. Nanba decidió enfocarse exclusivamente en el Maitake y, junto a otros científicos japoneses, comenzó la extracción de diversos polisacáridos para probar su potencial inmunomodulador y antineoplásico.
En 1984 Nanba identificó en el micelio y cuerpo frutal del maitake, una fracción con capacidad de estimular a los macrófagos. Esta fracción pudo ser obtenida del Maitake al tratar el cuerpo frutal del hongo con agua caliente y saturando los extractos hidrosolubles resultantes al 80% con alcohol etíllico. El precipitado luego es tratado con ácido acético y un material alcalino. La fracción resultante, denominada fracción-D es una forma estandarizada de compuestos polisacáridos beta- 1,6 y beta-1,3 glucan) y una proteína con un peso molecular cercano a 1.000.000.
Ese año el profesor Nanba obtiene la patente de este principio activo. A pesar de que otros hongos medicinales han demostrado contener beta-glucanes bioactivos, Nanba hace notar que existen diferencias entre los diferentes betaglucanes y que los beta-glucanos que se encuentran en la fracción-D del Maitake tienen una estructura única y compleja, conteniendo ambos: una cadena principal 1,6 con mayor grado de ramificaciones 1,3 y una cadena principal 1,3 con ramificaciones 1,6.
El ß-D-glucan básico es una estructura repetitiva, con sus moléculas de D-glucosa unidas en cadenas lineales por enlaces beta (ß). Estos pueden extenderse desde el carbono 1 de un anillo sacárido al carbono 3 del siguiente (ß1-3); del carbono 1 al carbono 4 (ß1-4) o desde el carbono 1 al carbono 6 (ß1-6). Frecuentemente existe una cadena principal ß1-3, ß1-4 o ß1-3, ß1-4 mezcladas con cadenas laterales ß1-6. La estructura repetitiva básica del ß1-3 glucan con cadenas laterales ß1-6 se observa en las figuras 1 y 2.
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Los Hetero-ß-D-glucanes, es decir, polímeros lineales de glucosa con otros D-monosacáridos, tienen actividad antineoplásica e inmunomoduladora, pero los alfa-D-glucanes usualmente carecen de estas propiedades.
Diez principios activos provenientes de hongos medicinales han demostrado eficacia clínica significativa en el tratamiento de las neoplasias humanas y el Sida, entre ellos destacan: la Fracción D, la Fracción MD, el Grifolan, los glucanes y proteoglucanes del Maitake. |
Figura 1  |
Diagrama molecular de mayor nivel de los beta-D-glucanes |
El beta 1,6 glucan es reconocido como el más efectivo agente estimulante de las respuestas inmunológicas celulares. Esta sustancia aumenta la actividad de los macrófagos y otras células inmunocompetentes que destruyen células tumorales, como los linfocitos NK (natural killers), linfocitos T citotóxicos (Tc), de 1,5 a 3 veces y de linfocitos T ayudadores CD4+ (T-helper), las células afectadas por el VIH. Maitake también mejora la eficiencia inmunológica de estas células, aumentando la producción de sustancias citotóxicas por parte de los macrófagos, de interleukina-1, interleukina-2 y linfokinas que activan los linfocitos T y de superóxido-aniones que eliminan células tumorales. El resultado final es un incremento de las defensas contra enfermedades infecciosas, SIDA y cáncer. |
El alto peso molecular de la fracción-D es uno de los factores que explica sus efectos inmunomoduladores, según se deduce de estudios sobre la actividad antitumoral y consumo de glucosa por parte de los macrófagos. La relación de ramificación y el peso molecular de los beta-1,3 glucanes también son factores importantes para la producción de citoquinas por parte de los macrófagos.
Los mecanismos antitumorales de las diversas especies de hongos medicinales, incluyendo al maitake, son mediadas por linfocitos T y macrófagos. A pesar de las similitudes estructurales y funcionales entre los diversos beta-glucanes micóticos, éstos difieren en su efectividad contra tumores específicos y su capacidad de elicitar diversas respuestas celulares, particularmente la produceión y expresión de citoquinas.
En la década de los noventa, el profesor Nanba, junto a su colaborador Keiko Kubo lograron una mayor purificación de la fracción-D, que condujo al aislamiento de un compuesto más potente, la fracción-MD, de la cual obtuvieron patente norteamericana. Esta fracción es un polvo higroscópico pardo, neutro a débilmente ácido, con un peso molecular cercano a 1.000.000.
La fracción MD es extraída y fraccionada a partir de micelios y cuerpos frutales de Grifola frondosa o G. albicans, G. umbellata , o G. gigantea . El proceso es similar al descrito en la patente japonesa para la fracción-D; sin embargo, Nanba y Kubo agregaron un paso adicional clave al proceso de la fracción-D, que remueve el sobrenadante mediante la adición de alcohol, lo que conduce a una concentración final del 20 a 60 % por volumen al extracto hidrosoluble de Grifola.
Los análisis demuestran que, al igual que la fracción-D, el principal componente de la fracción MD es un complejo glucano/proteína en rangos de 80:20 a 99:1.10. En esencia, las fracciones D y MD contienen la misma configuración de cadenas beta-glucanos, pero la fracción MD es más purificada y ofrece resultados significativamente superiores en los estudios antineoplásicos, inhibiendo el crecimiento tumoral, y estimulando las respuestas inmunes dependientes de macrófagos y linfocitos T killer.
Tanto la fracción D como la fracción MD son consideras seguras y libres de toxicidad. |
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Mecanismo de acción:
Los glucanes y proteoglucanes bioactivos aislados de hongos medicinales son la clase de inmunocéuticos más prometedores. Sin lugar a dudas, son capaces de aumentar todos los mediadores de las respuestas inmunes. Luego de décadas de experimentación con estas sustancias, se conocen muchos de sus mecanismos de acción, pero el sitio donde actúan parecen ser las células dendríticas o células de Langerhans.
Las células dendríticas, de las cuales las células de Langerhans son la variedad residente en la piel y mucosas, son capaces de detectar la amenaza constituida por sustancias exógenas o endógenas y movilizar las respuestas inmunológicas apropiadas.
Dada su amplia localización en los tejidos, las células dendríticas constituyen la primera línea de defensas de la Inteligencia Inmune. También son las primeras células en contacto con los glucanes administrados. Cuando los glucanes entran en la cavidad oral, son detectados por las células de Langerhans de la mucosa oral y luego por las células dendríticas de estómago e intestinos. Luego de ser absorbidos y circular hacia el hígado, las células de Kupffer (variedad de células dendríticas) pueden detectar estas sustancias. Los glucanes que llegan a los ganglios linfáticos son fagocitados por las células dendríticas de esos ganglios. Algunas moléculas de proteoglucanes son absorbidos y llegan intactos al torrente circulatorio donde estimulan la actividad fagocítica de los leucocitos.
La captación de glucanos y proteoglucanos activa las células dendríticas, actuando como estímulo antigénico. La proximidad de estas sustancias a la membrana celular de los linfocitos T (NK) resulta en su activación y aumento de sus acciones. La elevación de la actividad citotóxica de estos linfocitos se relaciona con una evolución postoperatoria favorable en pacientes con cáncer gástrico. La infiltración de glucanes y proteoglucanes en un tumor gástico humano antes de la resección quirúrgica, activó los linfocitos NK desarrollando actividad citotóxica significativa dirigida directamente contra el tumor. Similares resultados se han observado con la administración prolongada de estos principios activos en pacientes con cáncer vesical.
Los proteoglucanes también pueden activar a los linfocitos NK in situ en pacientes con cáncer. En varias pruebas, aumentó significativamente la actividad citotóxica de los linfocitos NK, aumentó significativamente los niveles de Interleukina-2 y mejoró significativamente la relación de células T CD4/CD8. Esto explica su utilidad como inmunoestimulante en casos de cáncer y sida.
Otra vía que explica la acción inmmunoestimuladora de los hongos medicinales es a través del incremento de las citocinas del sistema inmune. Sus principios activos pueden provocar la secreción de citocinas, incluyendo OOoooooo IL-1, IL-2, IL-6, IL-8, TNF (factor de necrosis tumoral) y varios interferones tanto como 5-120 veces los niveles basales.
En la Figura 3 se podrá observar el mecanismo de acción de los glucanes y proteoglucanes de los hongos medicinales. Muchos detalles de la acción inmunoestimulante de estos hongos no han sido precisados, sin embargo, su utilidad clínica ofrece ímpetus para la continuación de las investigaciones sobre sus mecanismos de acción.
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| Evidencias científicas :
Numerosos estudios han confirmado que el maitake ofrece importantes beneficios al sistema inmune. Promueve la acción de los macrófagos y de otras células del sistema INME, tales como linfocitos natural killer (NK) y células T-citotóxicas (Tc) que atacan a las células tumorales. Maitake también aumenta la eficiencia de las células inmunocompetentes aumentando los niveles de interleuquinas 1, 2 y linfoquinas. El resultado final es un aumento de los sistemas de defensas contra infecciones, SIDA y cáncer. Las fracciones de Maitake ofrecen acción antitumorales específicas, retardando el crecimiento de tumores de colon, pulmones, gástricos, hepáticos, prostáticos, cerebrales y de otros órganos. (Debe notarse que todas las referencias sobre la fracción-D aplican para la fracción MD, ya que se trata de los mismos beta 1,6/1,3 glucanes derivados de Grifola frondosa .)
Varios centros en los EEUU han comenzado a tratar pacientes con cáncer con las fracciones D y MD. Por ejemplo, en Febrero de 1998, la FDA norteamericana aprobó una aplicación como nueva droga investigacional (IND 54.589) para que investigadores condujeran un estudio piloto Fase II sobre los efectos potenciales de la fracción D en el tratamiento de neoplasias avanzadas de mama y próstata.
Los investigadores han identificado varias formas por las que Maitake puede beneficiar al paciente con cáncer:
• Evitando la malignización de células sanas
• Contribuyendo a prevenir metástasis
• Retardando o deteniendo el crecimiento tumoral
• Utilizado como coadyuvante a la quimioterapia, aumenta sus efectos positivos y disminuye sus efectos secundarios
En un estudio sobre el potencial preventivo del Maitake, se inyectó una sustancia carcinogénica (3-MCA, metilcolantreno). a un grupo ratones. Luego de 15 días de la inyección, 10 ratones fueron alimentados con 0,2 mg de la fracción D del Maitake, durante 15 días consecutivos. El grupo control recibió solo solución salina. Luego de 30 días, el número de ratones con cáncer fue 30,7% en el grupo que recibió Maitake y 93,2 % en el grupo control. El profesor Nanba sugirió que la fracción D del Maitake tiene una fuerte capacidad de estimular el sistema inmune.
En otro estudio, los investigadores expusieron a ratones a un conocido carcinógeno de la vejiga urinaria (N-butil-N'-butanolnitrosoamina; BBN) cada día durante ocho semanas y luego los alimentaron con hongos medicinales, incluyendo maitake, shiitake y otros. Todos los ratones tratados con BBN desarrollaron carcinoma de vejiga, pero en solo 46,7% de los ratones que recibieron Maitake aparecieron este tipo de tumores. Además, Maitake, así como los otros hongos, previnieron la depresión de la actividad de linfocitos y células NK.
En un estudio sobre la actividad anti-metastásica potencial del Maitake, los investigadores inyectaron células neoplásicas en las patas traseras de los ratones. Luego, se dividieron los ratones en tres grupos: el grupo control recibió alimentación normal, mientras que los otros grupos recibieron polvo total de Maitake como 20% de su dieta diaria o fracción D intraperitoneal a razón de 1 mg/kg por 10 veces. Luego de 30 días, el 100% de los ratones del grupo contol demostraron metástasis, en cambio, la fracción D previno 91,3% del total y el polvo total de Maitake previno un 81,3% (p<0.01). (Figura 1) |
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En otro estudio, los investigadores administraron fracción de polisacárido purificado de Maitake, a razón de 1 mg/kg/dia por vía intraperitoneal 24 horas después de implantar células tumorales MM-46 de carcinoma mamario; células de carcinoma-IMC de piel, o células de fibrosarcoma Meth-A en la región axilar de ratones machos. Luego de 25 días del implante, se extirparon los tumores sólidos y se pesaron para conocer la inhibición de su crecimiento. Maitake produjo una inhibición significativa del crecimiento tumoral, que osciló entre 25,6% para el fibrosarcoma Meth-A hasta 49 % para las células tumorales
MM-46.
En otro estudio con un diseño similar se probó una fracción de polisacáridos de beta-1,3 glucanos con ramificaciones 6, extraído del Maitake. Esta fracción mostró efectos antitumorales significativos contra células de fibrosarcoma Meth-A y células de carcinoma IMC, pero no inhibió el crecimiento de células leucémicas. Dosis orales de la fracción D también han demostrado actividad antitumoral significativa contra tumores alogénicos y singénicos.
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En otro estudio, los investigadores compararon los efectos de la fracción D y Mitomicina (un agente quimioterápico) en ratones con tumores. La fracción D sola inhibió el crecimiento tumoral más efectivamente que la Mitomicina sola (80% vs. 45%, respectivamente). La utilización concomitante de fracción D con Mitomicina fue aún más efectiva, alcanzando un 98% de inhibición del crecimiento tumoral. Este aparente efecto sinergístico entre Maitake y Mitomicina se atribuye a sus diferentes mecanismos de acción: Maitake estimula el sistema inmune y la Mitomicina ataca directamente a las células tumorales.
En 1994, un grupo de investigadores de China publicaron los resultados de sus estudios sobre 63 pacientes con cáncer. donde demuestran una efectividad total contra tumores sólidos mayor del 95 % y una efectividad contra leucemia mayor del 90%.
En 1995 el profesor Nanba realizó estudios clínicos preliminares sobre el uso de Maitake como coayuvante a la quimioterapia, utilizando la fracción D en pacientes con neoplasias en estadios avanzados. Un total de 165 pacientes con cáncer en estadios III-IV, de edades comprendidas entre los 25 a 65 años, participaron en el estudio y la data fue recogida con la colaboración de médicos pertenecientes a hospitales universitarios y clínicas de tratamiento contra el cáncer del Japón. |
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Estos pacientes recibieron tabletas con polvo de Maitake y fracción D o tabletas de polvo de Maitake, en dosis que oscilaron entre 4-6 gramos por día, junto a la quimioterapia. Se obtuvo mejoría sintomática o regresión en aproximadamente 73 % de los casos con cáncer de mama y 67 % de los casos con cáncer de pulmón. De los casos con cáncer hepático, 47 % respondieron, pero esta cifra saltó a 73 % cuando se agregó quimioterapia. Ochenta y tres % de los pacientes refirieron disminución del dolor y 90 % experimentaron mejoría de los síntomas relacionados con la quimioterapia, tales como: náusea, vómitos, pérdida del apetito, caída del cabello, sangramiento intestinal y leucopenia. (Figura 2) |
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La ingestión de Maitake previene el desarrollo de cáncer en 22,2% y la aparición de metástasis en 81,3% de los casos, lo que sugiere que puede contribuir a la reducción de los riesgos de padecer cáncer.
Por otra parte, varios médicos norteamericanos han reportado buenos resultados con Maitake en sus consultas y en 1998 se obtuvo una aprobación como nueva droga de investigación para iniciar los estudios pilotos de segunda fase, en pacientes con cáncer avanzado de mama o próstata.
Maitake ha sido utilizado exitosamente en tumores de mama, hígado, pulmón, próstata, SNC, colon, fibroadenomas uterinos, leucemia, metástasis pulmonares, linfoma de Hodgkin y el Síndrome de Inmunodeficiencia adquirida.
Por otra parte, el Maitake potencia los efectos de los suplementos de Cartílago de Tiburón (que inhibe la angiogénesis tumoral).
Aunque no se puede afirmar que el Maitake constituye la cura del cáncer, mantiene la calidad de vida de los pacientes y potencia el sistema inmune, lo que resulta en una remisión de las células cancerosas y una mejoría de los parámetros inmunológicos, sin efectos secundarios.
Maitake y Virus de la Inmunodeficiencia Humana (VIH)
A finales de la década de los ochenta, investigadores japoneses determinaron en un estudio sobre animales que las dosis orales de fracción D mejoraron los linfocitos T ayudadores (T helper), las células blanco del VIH. Este fue una de las primeras muestras clínicas de que el Maitake puede ser un tratamiento potencial para el VIH.
En Noviembre de 1991 una fracción de Maitake sulfatada demostró ser activa en pruebas preliminar de medicamentos anti-VIH, conducidas por el National Cancer Institute (NCI), de los EEUU. Según esta institución, el Maitake demostró una actividad antiretroviral significativa, dependiente de la dosis.
Desde entonces, diversos estudios sobre los efectos inmunomoduladores del Maitake soportan su uso contra el VIH. La fracción MD también fue evaluada en un estudio a largo plazo en humanos, para conocer su potencial de beneficio para los pacientes infectados con el VIH.
Nanba y colaboradores estudiaron los efectos de tabletas con 6 gramos de Maitake y dosis de 20 mg de fracción MD juto a tabletas de 4 gramos, ingeridas diariamente durante un año en 35 pacientes seropositivos. Los investigadores monitorearon el número de CD4+ (células T-helper), carga viral, síntomas de infección por VIH, presencia de enfermedades secundarias y sensación de bienestar. Los efectos sobre los recuentos de células T-helper y carga viral fueron variables: el recuento de células T helper aumentó en 20 pacientes, disminuó en 8 y se mantuvo estable en 4. La carga viral disminuyó en 10 pacientes, aumentó en 9 y se mantuvo estable en 2. Ochenta y cinco% de los pacientes reportaron un aumento en la sensación de bienestar relacionada con diversos síntomas y enfermedades secundarias propiciadas por el VIH. Los investigadores concluyeron que la fracción MD actúa en varios niveles: inhibe directamente al VIH; estimula los sistemas inmunes de defensa contra el VIH y enfermedades oportunistas.
Estudios preliminares, no publicados sugieren que el extracto líquido de la fracción D mezclado con dimetilsulfoxido, aplicadas tópicamente pueden utilizarse en el tratamiento del Sarcoma de Kaposi, que acompaña al SIDA.
Por otra parte, varios médicos norteamericanos han reportado buenos resultados con Maitake en sus consultas y en 1998 se obtuvo una aprobación como nueva droga de investigación para iniciar los estudios pilotos de segunda fase, en pacientes con cáncer avanzado de mama o próstata.
Por otra parte, el Maitake potencia los efectos de los suplementos de Cartílago de Tiburón (que inhibe la angiogénesis tumoral).
Aunque no se puede afirmar que el Maitake constituye la cura del cáncer o el SIDA, mantiene la calidad de vida de los pacientes y potencia el sistema inmune, lo que resulta en una remisión de las células cancerosas y una mejoría de los parámetros inmunológicos, sin efectos secundarios.
Otros efectos
Los japoneses reconocen al Maitake desde hace mucho tiempo, como un tónico o adaptógeno, sustancia que balancea las funciones corporales y ofrece bienestar, vitalidad, fuerza y vigor. Los médicos que han prescrito este hongo medicinal han reportado que mejora los casos de síndrome de fatiga crónica, infecciones vaginales persistentes por Candida albicans y fibromas uterinos.
Los estudios realizados con polvo total de Maitake y otras presentaciones durante las últimas dos décadas sugieren que puede jugar un papel importante en el tratamiento de otras enfermedades.
Diabetes
Por lo menos dos estudios sugieren que Maitake tiene un efecto terapéutico contra la diabetes. En uno de ellos, investigadores japoneses alimentaron a ratones diabéticos con una dieta contentiva de 20% de polvo total de Maitake, durante 8 semanas, lo que demostró la inhibición de los aumentos de glucosa sanguínea. Los investigadores también observaron la actividad hipoglicemiante de la fracción X, concluyendo que Maitake es efectivo para disminuir la glucosa sanguínea en animales diabéticos. Un estudio posterior, realizado por Kubo y Nanba, también realizado con ratones diabéticos, demostró que Maitake inhibió la elevación de glucosa sanguínea, efectos relacionados con los receptores de insulina. Los autores sugieren que el Maitake aumenta la sensibilidad a la insulina.
Hipertensión arterial
EL polvo total de Maitake ha demostrado, en estudios animales, disminuir la presión arterial y prevenir su ascenso. La alimentación de ratas hipertensas con polvo total de Maitake (5% de la dieta) durante 9 semanas, redujo significativamente la presión arterial. Un protocolo similar de alimentación durante 8 semanas, iniciado cuando las ratas tenían 10 semanas de edad e hipertensión arterial establecida, también fue exitoso. Los investigadores concluyeron que los resultados demuestran que Maitake evita el desarrollo de hipertensión y también disminuye las cifras tensionales elevadas.
Colesterol y Triglicéridos
Varios estudios han examinado los efectos del Maitake sobre los lípidos séricos, incluyendo colesterol y triglicéridos. En un estudio publicado en 1988, ratas hipertensas fueron alimentadas con una mezcla al 5% de polvo total de Maitake, lo que disminuyó significativamente los niveles de VLDL y colesterol total. Otro estudio conducido en ratas alimentadas con dietas con alto contenido de colesterol junto a 20% de con polvo total de Maitake demostró que el Maitake inhibió la acumulación hepática de grasas y produjo una reducción del colesterol total.
En otro estudio con similar protocolo, las ratas alimentadas con Maitake experimentaron reducción significativa y prolongada del colesterol y triglicéridos séricos, manteniendo similares nivles de HDL colesterol.
Hepatopatías
Varios estudios sugieren que Maitake puede tambén ser efectivo en la prevención y tratamiento de enfermedades hepáticas. A principios de la década de los noventa, investigadores chinos condujeron un estudio piloto sobre 32 pacientes con hepatitis B crónica. En un simposio internacional que se llevó a cabo en China en 1994, los investigadores presentaron sus resultados en los que se demuestra que los pacientes que recibieron Maitake tuvieron signos positivos de mejoría (disminución de los valores de transaminasas), comparados con pacientes del grupo control.
En otro estudio, un grupo de ratas fueron alimentadas con una dieta alta en colesterol y midieron los efectos de complementar esa dieta con 20% de polvo total de Maitake. Los investigadores demostraron que el Maitake inhibió la acumulación de grasas hepáticas.
En otro estudio, los investigadores alimentaron a ratones con daño hepático autoinmune crónico, demostrando mejoría significativa.
Obesidad
Maitake ofrece algunas vitaminas del complejo B, ergosterol/provitamina D2, magnesio, potasio, calcio, ácidos grasos insaturados, fosfatidilserina y otros fosfolípidos, y proteínas. Aunque no contiene vitaminas A o C, se han identificado sustancias con propiedades químicas similares al ácido ascórbico. Debido a que el Maitake es rico en fibras y bajo en calorías y grasas, se le ha citado como producto natural que puede contribuir al control del sobrepeso. Estudios animales han demostrado que la suplementación dietaria con Maitake puede inhibir la ganancia de peso. Cuando se alimentó a ratas con polvo seco de Maitake, como 20% en peso de una dieta alta en colesterol, inhibió significativamente los aumentos de peso y grasa corporal. Un protocolo similar demostró mejoría del metabolismo lipídico en las ratas alimentadas con Maitake. Estos animales pesaron 24,9% menos que las ratas control al frinalizar el estudio. Las pruebas realizadas en ratas hipertensas alimentadas con Maitake también demostraron un efecto inhibidor de la ganacia poneral. En un estudio clínico conducido en 30 pacientes con sobrepeso, los investigadores ofrecieron tabletas equivalentes a 200 gramos de Maitake fresco diariamente durante dos meses. Todos los pacientes perdieron peso, sin realizar ninguna dieta. La pérdida de peso en promedio fue de 7-13 libras y uno de los sujetos perdió 26,4 libras. |
Medicina Sistémica y Maitake
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Dosis :
Recomendamos la ingestión de 2 a 3 cápsulas, tres veces por día, con las comidas.
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Toxicidad/ Efectos secundarios:
No se ha descrito toxicidad alguna en ninguno de los estudios en animales o seres humanos. Raramente puede ocasionar evacuaciones flojas, situación que desaparece al disminuir la dosis.
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Contraindicaciones :
Ninguna. El Maitake es un alimento consumido diariamente en las culturas asiáticas, desde hace siglos .
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Conclusión :
En Japón y China existe una tendencia considerablemente avanzada hacia la integración de agentes inmunoestimulantes con la cirugía, quimio y radioterapia para el tratamiento del cáncer. En estos países las preparaciones con hongos medicinales constituyen un recurso terapéutico contra el cáncer desde hace siglos. En los países occidentales, el manejo proactivo del cáncer ha sido relegado, a pesar del fracaso de la medicina convencional para curar neoplasias comunes y la asequibilidad de excelentes evidencias clínicas que soportan el uso de hongos inmunocéuticos. En un futuro muy cercano, los dogmas desaparecerán para dar paso a la inmunoterapia con hongos micóticos, mejorando así la calidad de vida y la tasa de supervivencia de los pacientes con cáncer o sida.
Una de las causas frecuentes de muerte en el paciente con cáncer son las metástasis, que ocurren con o sin invasión de los tejidos vecinos por los tumores. La cirugía comúnmente reduce la masa tumoral y la quimio y radioterapia a menudo reduce los tumores y minimiza su invasividad y metástasis. Sin embargo, estas terapias tóxicas invariablemente afectan la Inteligencia Inmune del huésped y pequeñas cantidades de células malignas sobreviven los mejores esfuerzos para erradicarlas. La capacidad de mejorar la Intelgencia Inmune para que actúe contra los tumores y sus metástasis, al mismo tiempo que se potencia la capacidad de destrucción de la quimioterapia y se disminuyen sus efectos adversos, convierte a la inmunoterapia con hongos medicinales en una opción clínicamente atractiva para los oncólogos que realmente desean lo mejor para sus pacientes.
Los hongos medicinales se comparan favorablemente con otros modificadores de las respuestas biológicas, tales como: la vacuna BCG, OK-432, células LAK o citosinas purificadas (como interferones, factor de necrosis tumoral, o Interleukina-2). Todas estas sustancias son capaces de causar efectos secundarios, como fiebre, escalofríos, erupciones, edema, artralgias, hipotensión arterial, insuficiencia cardíaca congestiva o toxicidad a nivel del sistema nervioso central. Los hongos medicinales no producen ningún efecto adverso y ningún tipo de intolerancia, lo que los convierte en inmunocéuticos de primera elección en el manejo del cáncer. De hecho, los médicos progresistas los han utilizado desde hace años.
Los perfiles riesgo-beneficio y costo-beneficio de los hongos medicinales son superiores a los fármacos antineoplásicos y anti-retrovirales. Además de que su administración durante períodos prolongados es segura, mejoran los niveles de energía del paciente, aceleran la recuperación de la médula ósea afectada, protegen y recuperan las funciones hepáticas, disminuyen los efectos secundarios de las terapias anticancerosas y antiretrovirales, al mismo tiempo que incrementan la sensación de bienestar.
Los glucanes y proteoglucanes están ganando rápidamente respeto como terapias antineoplásicas efectivas. Estudios controlados, doble-ciego demuestran que mejoran la calidad de vida en más del 70 % de los pacientes con cáncer.
El aumento de la sobrevida que alcanzan los pacientes tratados con estos hongos medicinales por cáncer o sida en de gran importancia clínica. Utilizados en combinación, tienen el potencial de prolongar la supervivencia.
Maitake ofrece esperanzas a los pacientes con cáncer o sida. Sus prioncipios activos contribuyen a mantener la homeostasis, son potentes inmunoestimulantes que no producen fenómenos auto-inmunes. Como suplemento dietético es seguro y ofrece un perfil casi perfecto de riesgo-beneficio. Los hongos medicinales resultan imprescindibles para cualquier paciente con cáncer, sida u enfermedades caracterizadas por la depresión inmune. |
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Referencias
1: Oncol Rep. 2005 Mar;13(3):497-502.
Enhancement of cytotoxicity of NK cells by D-Fraction, a polysaccharide from Grifola frondosa.
Kodama N, Asakawa A, Inui A. Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Higashinada-ku, Kobe, Japan.
In innate immunity, activated natural killer (NK) cells attack and damage pathogens such as bacteria and virus without restriction by the MHC antigen. NK cells activated by IL-12 have been reported to recognize and kill tumor cells in perforin-mediated apoptosis. We have reported that D-Fraction, a polysaccharide extracted from the maitake mushroom (Grifola frondosa), activates macrophages, dendritic cells, and T cells and inhibits the growth of tumor cells. However, the effects of D-Fraction on NK cell function in the innate immune response are not well known. In the present study, we administered D-Fraction to MM-46 mammary tumor-bearing C3H/HeJ mice intraperitoneally for 3 consecutive days and investigated its effects on the activation and cytotoxicity of NK cells. D-Fraction significantly enhanced the cytotoxicity against NK-sensitive YAC-1 cells and the expression of CD223 on NK cells. D-Fraction also increased the expression of CD86 on macrophages. In addition, the levels of IL-12 in the culture supernatant of whole spleen cells and in serum increased, compared with the control corresponding to an increase in expression of IL-12 receptor betaI on NK cells. These results suggest that D-Fraction enhances the cytotoxicity of NK cells through the production of IL-12 by macrophages activated by D-Fraction.
2: Intern Med. 2004 Aug;43(8):737-40.
Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol.
Tanaka H, Tsunematsu K, Nakamura N. Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
We successfully treated a patient with occupational hypersensitivity pneumonitis (HP) caused by Grifola frondosa (Maitake) mushroom spore with an extra-fine aerosol corticosteroid; beclomethasone dipropionate (BDP) dissolved in hydrofluoroalkane-134a (HFA). A 49-year-old woman developed respiratory symptoms 3 months after beginning work on a mushroom farm. She was diagnosed as HP based on radiological and serological findings. Oral prednisolone therapy improved her HP and she returned to the same farm. Her HP relapsed after 5 months, and daily 400 microg of HFA-BDP was administered with gradual improvement. An extra-fine particle inhaled corticosteroid might reach appropriate alveoli to be effective therapy for mild HP.
Publication Types:
• Case Reports
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3: J Med Food. 2004 Summer;7(2):141-5.
Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice.
Kodama N, Murata Y, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. |
We have reported that D-Fraction, a polysaccharide extracted from the edible maitake mushroom (Grifola frondosa), activates immunocompetent cells, thereby eliciting antitumor activity. To extend the application of D-Fraction as a nutritional supplement for healthy people as well as treatment for those with cancer, we investigated the effects of D-Fraction on the immune system in normal C3H/HeJ mice. Splenocytes from mice administered D-Fraction intraperitoneally for 17 consecutive days were cultured, and the culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-12 production by antigen-presenting cells (APCs), including macrophages and dendritic cells, and also for the T helper (Th)-1 cytokine interferon (IFN)-gamma and the Th-2 cytokines IL-4 and IL-10. The level of IL-10 as well as those of NO and IFN-gamma were increased by D-Fraction as compared with the control, in which the serum immunoglobulin E level was increased. The results suggest that D-Fraction induced a Th-2 dominant response through the activation of macrophages, resulting in the enhancement of humoral immunity rather than cell-mediated immunity. Furthermore, an increase in the percentage ratio of CD69 and CD89 expression on major histocompatibility complex II(+) cells revealed activation of APCs 4 h after D-Fraction administration. These results indicate that D-Fraction enhances both the innate and adaptive arms of the immune response in normal mice. Therefore, its administration may enhance host defense against foreign pathogens and protect healthy individuals from infectious diseases.
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4: J Ethnopharmacol. 2004 Jul;93(1):75-81.
Effect of medicinal plant extracts on forced swimming capacity in mice.
Jung K, Kim IH, Han D. Food Processing Technology, Korea Food Research Institute, Baekhyun-dong, Bundang-ku, Songnam-si, Kyonggi-do, Republic of Korea. |
The tonic effect of Cordyceps militaris (CM), Paecilomyces japonia (PJ), Phellinus linteus (PL), Ganoderma lucidum (GL), Grifola frondosa (GF), and Panax ginseng (PG) was examined based on the forced swimming capacity and the change of biochemical parameters in ICR mice. The treatment groups were orally administered medicinal plant extracts (500 mg/kg per day), while the control group received distilled water for 4 weeks. The swimming times to exhaustion were longer in the CM, PJ, and GF groups than in the control group (P < 0.05). Plasma TG levels were lower in the treatment groups than in the control group. Plasma glucose levels were not significantly different between the control group and each treatment group except the PG group. Plasma lactate and ammonia levels of the PJ and GF groups were lower than those of the control group (P < 0.05). There were no significant differences in the content of liver and gastrocnemius muscle glycogen between the control group and each treatment group. In conclusion, PJ and GF extracts enhanced the forced swimming capacity of mice by increasing fat utilization and by delaying the accumulation of plasma lactate and ammonia.
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5: Res Commun Mol Pathol Pharmacol. 2002;112(1-4):68-82.
Effects of Maitake mushroom fractions on blood pressure of Zucker fatty rats.
Talpur N, Echard B, Dadgar A. Department of Physiology, Medicine and Pathology, Georgetown University Medical Center, Washington, DC, USA.
A link exists between insulin resistance and many chronic disorders of aging including advancing-age. A safer means to prevent or, at least, slow the erosion of insulin sensitivity would provide a novel approach to better health. We compared the ability of a specific extract labeled fraction SX, as well as whole Maitake powder, fraction ES and fraction D of Maitake to influence SBP and various pertinent biochemical parameters when given orally to Zucker Fatty rats, a model of insulin resistance and type 2 diabetes mellitus. A secondary gain was the ability to ascertain the effects of bitter melon, olive oil, and sesame oil alone and combined with fraction SX to influence SBP. We found that a water-soluble fraction obtained from Maitake mushroom (SX) lowers SBP and fasting blood glucose significantly over the three to six weeks of study. While whole Maitake fraction lowered SBP effectively, the effects on fasting blood sugar were not apparent under the conditions of study. In contrast to fraction SX and fraction D, developed primarily to enhance immunity and suppress tumor development and growth, has essentially no effect on SBP under the conditions examined. An ether soluble fraction designated ES lowers SBP significantly. Interestingly, olive oil, unlike sesame oil, also lowers SBP. Finally, bitter melon and a combination of SX plus bitter melon also lower SBP. We conclude that fraction SX of Maitake mushroom may be useful to treat insulin resistance alone or combined with other natural products such as bitter melon and niacin-bound chromium.
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6: J Med Food. 2003 Winter;6(4):371-7.
Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients.
Kodama N, Komuta K, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. |
Maitake D-Fraction, extracted from maitake mushroom, has been reported to exert its antitumor effect in tumor-bearing mice by enhancing the immune system through activation of macrophages, T cells, and natural killer (NK) cells. In a previous study, the combination of immunotherapy with the maitake D-Fraction and chemotherapy suggested that the D-Fraction may have the potential to decrease the size of lung, liver, and breast tumors in cancer patients. In the present study, we administered maitake D-Fraction to cancer patients without anticancer drugs, and at the same time NK cell activity was monitored to investigate whether the activity is closely related with disease progression. The numbers of CD4(+) and CD8(+) cells in the peripheral blood were measured in 10 patients, and NK cell activity was assessed using K-562 cells as target cells. Serum soluble interleukin-2 receptor (sIL-2R) levels in three patients and the expression of tumor markers in four patients were determined by enzyme-linked immunosorbent assay. The slight changes observed in the CD4(+) and CD8(+) cell numbers were independent of disease severity or stage as well as serum sIL-2R levels. In contrast, maitake D-Fraction hindered metastatic progress, lessened the expression of tumor markers, and increased NK cell activity in all patients examined. Thus maitake D-Fraction appears to repress cancer progression and primarily exerts its effect through stimulation of NK activity. In addition, we conclude that measurement of NK cell activity may be a useful clinical parameter in monitoring disease progression during and following immunotherapy with maitake D-Fraction.
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7: Mol Cell Biochem. 2003 Oct;252(1-2):369-77.
Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats.
Talpur N, Echard BW, Yasmin T. Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA. |
Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (-)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70-75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (-)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4-6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.
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8: Zhong Yao Cai. 2003 Jan;26(1):31-2.
Anti-tumor effect of polysaccharide from Grifola frondosa and its influence on immunological function
Li X, Rong J, Wu M. Department of Food Science and Technology, Huazhong Agricultural University, Wuhan, PR China.
When the polysaccharide from Grifola frondosa (PGF) was taken orally by S180 bearing mice at the dosage of 50-150 mg/kg.d for 9 d, the inhibitory rate to S180 was 27.97%-38.46%. The PGF can also enhance thymus index, the ability of splenic lymphocyte proliferation and formation of antibody in splenic cells, and promote the production of IgM hemolysin significantly in S-180 bearing mice.
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9: Cancer Lett. 2003 Mar 31;192(2):181-7.
Relationship between dendritic cells and the D-fraction-induced Th-1 dominant response in BALB/c tumor-bearing mice.
Harada N, Kodama N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyama-kitamachi, Higashinada-ku, Kobe, Japan. |
Dendritic cells (DCs) are known to not only induce the activation of T cells, but are also associated with the differentiation of T cells. The D-fraction, a beta-glucan extracted from maitake (Grifola frondosa) which expresses anti-tumor effects by establishing a helper (Th)-1 dominance in BALB/c mice, enhanced IL-12p70 production by DCs, when the ratio of CD8alpha(+) DCs to CD8alpha(-) DCs increased. In addition, examination of the tumor rejection effect of D-fraction-stimulated DCs loaded with tumor antigen revealed that tumor growth is inhibited completely by activating CD4(+) T cells and CD8(+) T cells.
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10: Jpn J Pharmacol. 2002 Dec;90(4):357-60.
A polysaccharide, extract from Grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice.
Kodama N, Harada N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
A polysaccharide, designated as the D-fraction, extracted from maitake (Grifola frondosa), was reported to have anti-tumor effects by activating macrophages and T cells in C3H/HeN mice in which a Th-1 dominant response was established. In this study using BALB/c mice in which a Th-2 response is genetically dominant, D-fraction reduced the expression of Th-2 cytokine interleukin (IL)-4 but markedly increased the expression of Th-1 cytokine interferon (IFN)-gamma in CD4(+) T cells and also increased IL-12p70 production as well as IFN-gamma production by antigen-presenting cells (APCs), suggesting that D-fraction promotes the differentiation into Th-1 cells of CD4(+) T cells through enhancement of IL-12p70 production by APCs.
11: Biol Pharm Bull. 2002 Dec;25(12):1647-50.
Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells.
Kodama N, Komuta K, Sakai N. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
Natural killer (NK) cells are directly cytotoxic for tumor cells and play a primary role in regulating immune responses. We monitored levels of NK cell cytotoxic activity in cancer patients receiving D-Fraction extracted from maitake mushrooms (Grifola frondosa). Elevated levels of cytotoxic activity were maintained for one year. To elucidate the mechanisms underlying long-term activation of NK cells during treatment with D-Fraction, we examined tumor volume and levels of IFN-gamma and TNF-alpha in MM46-bearing C3H/HeN mice to which D-Fraction was administered for 19 d. D-Fraction markedly suppressed tumor growth, corresponding with increases in TNF-alpha and IFN-gamma released from spleen cells and a significant increase in TNF-alpha expressed in NK cells. This suggests that the D-Fraction activates NK cells even on the 20th day after treatment. Furthermore, D-Fraction increased macrophage-derived interleukin (IL)-12, which serves to activate NK cells. These results suggest that NK cells are not only responsible for the early effects of D-Fraction on tumor growth, but also for the long-term tumor-suppressive effects of D-Fraction through increased IL-12 released from macrophages.
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12: J Agric Food Chem. 2002 Dec 18;50(26):7581-5.
Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa.
Zhang Y, Mills GL, Nair MG. Bioactive Natural Products Laboratory, Department of Horticulture and National Food Safety and Toxicology Center, Biosystems Engineering, Michigan State University, USA. |
The bioassay-guided isolation and purification of the hexane extract of the cultured mycelia of Grifola frondosa led to the characterization of a fatty acid fraction and three compounds, ergosterol (1), ergostra-4,6,8(14),22-tetraen-3-one (2), and 1-oleoyl-2-linoleoyl-3-palmitoylglycerol (3). The composition of fatty acid fraction was confirmed as palmitic, oleic, and linoleic acids by GC-MS and by comparison with the retention values of authentic samples. The structures of compounds 1-3 were established by spectroscopic methods. The fatty acid fraction and compounds 1-3 showed cyclooxygenase (COX) enzyme inhibitory and antioxidant activities. The inhibition of COX-1 enzyme by the fatty acid fraction and compounds 1-3 at 250 microg/mL were 98, 37, 55, and 67%, respectively. Similarly, COX-2 enzyme activity was reduced by fatty acid fraction and compounds 1-3 at 250 microg/mL by 99, 37, 70, and 4%, respectively. The inhibitions of liposome peroxidation by the fatty acid fraction and compounds 1 and 2 at 100 microg/mL were 79, 48, and 42%, respectively. This is the first report of compounds 2 and 3 from the cultured mycelia of G. frondosa. The COX inhibitory activities of compounds 1-3 are reported here for the first time.
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13: J Altern Complement Med. 2002 Oct;8(5):573-80.
Chemosensitization of carmustine with maitake beta-glucan on androgen-independent prostatic cancer cells: involvement of glyoxalase I.
Finkelstein MP, Aynehchi S, Samadi AA. Department of Urology, New York Medical College, Valhalla, NY, USA. |
OBJECTIVE: To improve the poor efficacy (< 10%) of chemotherapy for patients with hormone-refractory prostate cancer, we investigated a possible cytotoxic effect of carmustine/beta-glucan combination on prostatic cancer PC-3 cells, focusing on a glutathione-dependent detoxifying enzyme, glyoxalase I (Gly-I). METHODS: Carmustine (BCNU) is an anticancer agent and a putative inhibitor of Gly-I, while beta-glucan is a unique, nontoxic polysaccharide extracted from maitake mushrooms. The cytotoxic effects of BCNU or other anticancer agents with beta-glucan on PC-3 cells were assessed by cell-viability testing and Gly-I activity was measured using the spectrophotometric method. RESULTS: BCNU, 5-fluorouracil (5-FU), and methotrexate (MTX) were capable of inducing approximately a 50% reduction in cell viability at 72 hours, while etoposide, cisplatin, and mitomycin C were all ineffective. Only the combination of BCNU (50 micro ;mol) and beta-glucan (60 micro g/mL) exhibited an enhanced cytotoxicity with an approximate 90% cell viability reduction, but little improvement was seen with any combinations of 5-FU, MTX, or beta-glucon. Gly-I assays revealed that such a profound (approximately 90%) cell death was accompanied by an approximate 80% reduction in Gly-I activity by 6 hours. CONCLUSION: This study demonstrates a sensitized cytotoxic effect of BCNU with beta-glucan in PC-3 cells, which was associated with a drastic (approximately 80%) inactivation of Gly-I. Therefore, the BCNU/beta-glucan combination may help to improve current treatment efficacy by targeting Gly-I, which appears to be critically involved in prostate cancer viability.
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14: Mol Cell Biochem. 2002 Aug;237(1-2):129-36.
Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains.
Talpur NA, Echard BW, Fan AY. Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA. |
Maitake mushroom has been reported to favorably influence hypertension and diabetes mellitus. The purpose of this study was to compare the effects of whole Maitake mushroom powder and two extracts designated as ether soluble (ES) and water soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and on spontaneously hypertensive rats (SHR), a model of genetic hypertension. In the initial study, we followed four groups of eight ZFR and SHR receiving special diets: a baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD + fraction ES (0.10% w/w), and BD + WS (0.22% w/w). Different effects of these dietary regimens on the 2 rat strains were found. At 35 days, only consumption of the ES diet significantly decreased systolic BP (SBP) in SHR (average 197 vs. 176 mm Hg, p < 0.001), while in ZFR only the groups consuming the whole Maitake and WS diets showed significantly decreased SBP (138 vs. 120-125 mm Hg, p < 0.001). A challenge test with losartan (an angiotensin II receptor blocker) indicates that angiotensin II does not play a major role in SBP regulation of ZFR, but does in SHR where consumption of ES relative to other groups significantly lowered activity of this system. In SHR, glucose, cholesterol, circulating insulin and HbA1C were virtually similar among all dietary groups; but whole Maitake (-22%), ES (-120%) and WS (-80%) diets were associated with decreased triglycerides, and the ES diet with lowered serum creatinine (-29%). In ZFR, circulating insulin and HbA1C were significantly decreased in the whole Maitake powder and ES groups, and tended to be lower in the WS group compared to control. In the ensuing studies, we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg fraction WS plus 100 microg niacin-bound chromium (NBC). Oral gavage of WS clearly lowered SBP and circulating glucose concentrations, more so with the addition of chromium. We conclude that the examined forms of Maitake mushroom have antihypertensive and antidiabetic potential which differ among rat strains. The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin system.
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15: Altern Med Rev. 2002 Jun;7(3):236-9.
Can maitake MD-fraction aid cancer patients?
Kodama N, Komuta K, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
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Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer.
Publication Types:
• Case Reports
• Review
• Review, Tutorial
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16: Biol Pharm Bull. 2002 Apr;25(4):536-40.
Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph node Th-1/Th-2 proportion.
Inoue A, Kodama N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
We have already reported that the D-Fraction, a beta-glucan extracted from the fruiting body of the maitake mushroom (Grifola frondosa), activates cellular immunity and expresses anti-tumor effects. In this study we investigated the anti-tumor functions of D-Fraction in relation to its control of the balance between T lymphocyte subsets Th-1 and Th-2. D-Fraction decreased the activation of B cells and potentiated the activation of helper T cells, resulting in enhanced cellular immunity. It also induced the production of interferon (IFN)-gamma, interleukin (IL)-12 p70, and IL-18 by whole spleen cells and lymph node cells, but suppressed that of IL-4. These results suggest that D-Fraction establishes Th-1 dominance which induces cellular immunity in the population that was Th-2 dominant due to carcinoma.
17: J Exp Clin Cancer Res. 2001 Dec;20(4):591-7.
Nitric oxide-mediated antitumor activity induced by the extract from Grifola frondosa (Maitake mushroom) in a macrophage cell line, RAW264.7.
Sanzen I, Imanishi N, Takamatsu N. Dept. of Clinical Nursing, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
We have investigated D-fraction (MDF) extracted from Grifola frondosa (Maitake mushroom) on the inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production in RAW264.7 (RAW) cells, a murine monocyte/macrophage cell line, with special reference to antitumor activity of MDF against human hepatoma-derived huH-1 cells. MDF could induce iNOS mRNA expression in RAW cells in a dose range of more than 30 microg/ml, but the effect of 10 microg/ml of MDF was negligible. The iNOS mRNA expression induced by 100 microg/ml of MDF was 6 hrs later, but lasted for a longer time than that of lipopolysaccharide (LPS), a representative iNOS inducer. Although iNOS mRNA levels in MDF-stimulated cells were almost equal to LPS-stimulated cells at the peak time, the cumulative amount of nitrite was only about 50% compared with that of LPS-treated cells. When huH-I cells were cultured in MDF containing media in a 24-well plate with inserted porous bottom in the presence or absence of RAW cells, the viability of huH-1 cells decreased significantly only in the presence of RAW cells in MDF dose-dependent manner. This antitumor activity of RAW cells in the presence of MDF was abolished or attenuated by the addition of L-NAME, a NOS inhibitor, confirming that this phenomenon is due to iNOS-mediated NO production by RAW cells, but not direct cytotoxic activity of MDF against huH-1 cells. These data suggest that MDF is a novel inducer for iNOS which contributes at least in part to antitumor activity of MDF.
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18: Diabetes Obes Metab. 2002 Jan;4(1):43-8.
Effects of a water-soluble extract of maitake mushroom on circulating glucose/insulin concentrations in KK mice.
Manohar V, Talpur NA, Echard BW. Department of Physiology, Georgetown University Medical Center, Washington, DC, USA. |
AIM: We examined benefits of a water-soluble extract of maitake mushroom designated as Fraction X (FXM) on the glucose/insulin metabolism of insulin-resistant KK mice, and compared the results of FXM with those of a sulphonylurea, Glipizide. DESIGN: In several acute studies, insulin-resistant KK mice were gavaged with a single dose of varying concentrations of FXM, or a single dose of one concentration of the oral hypoglycaemic drug, Glipizide. In the one chronic study, KK mice were gavaged with FXM, Glipizide, or an equal volume of isotonic saline (baseline control) twice daily. Retro-orbital blood was drawn on the morning of the 4th and 7th days before the early gavage. Blood glucose was measured by routine laboratory procedures, and serum insulin was estimated by a radioimmunoassay (RIA) assay developed specifically for rodents. RESULTS: At a dose of FXM (140 mg/mouse), a statistically significant lowering of circulating glucose concentrations was again seen at 8-12 h and 16-18 h after oral gavage. The lowering approximated 25% of the original concentration. Oral gavage of Glipizide resulted in statistically significantly lower values of circulating glucose (25-37% lower compared with baseline) at 8-24 h post dosing. In the chronic study, the circulating concentrations of glucose and insulin of mice taking 140 mg FXM per day were decreased significantly at days 4 and 7. CONCLUSIONS: FXM, a natural extract obtained from maitake mushroom, favourably influences glucose/insulin metabolism in insulin-resistant KK mice. The lowering of both circulating glucose and insulin concentrations suggests that FXM works primarily by enhancing peripheral insulin sensitivity.
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19: Zhonghua Wai Ke Za Zhi. 1999 Aug;37(8):464-5.
Prevention of postoperative recurrence of bladder cancer: a clinical study
Yang D, Li S, Wang H. Department of Urolagy, Jinan General Hospital of People's Liberation Army, Jinan, PR China.
OBJECTIVE: To lower postoperative recurrence rate of bladder cancer, the prophylactic effects of five kinds of method on bladder cancer were evaluated. METHODS: Between 1982 and 1997, 313 patients after TURBT or partial cystectomy were followed up for 2 to 15 years (average 7.6 years). These patients were divided into six groups: BCG, mytomycin C (MMC), thiotepa, Chinese herb medicine Zhuling (Grifola umbellata pilat), afterloading brachytherapy and control group. The prophylactic effects of them on postoperative recurrence of bladder cancer was evaluated. RESULTS: During the follow-up, the recurrence rates were 35.1% in BCG group, 34.9% in Zhuling group, 41.7% in MMC group, 52.6% in thiotepa group, 64.7% in control group, respectively. 25 high-risk patients with invading or multiple bladder cancer were treated by afterloading brachytherapy. They were followed up from 12 to 42 months, with a recurrence rate being 24.0%. CONCLUSIONS: The prophylactic effect of Zhuling and BCG on bladder cancer recurrence was better than MMC. The vale of thiotepa was not significant. The afterloading brachytherapy was of great vale to invading or recurrent, multiple bladder cancer.
20: Jpn J Pharmacol. 2001 Dec;87(4):327-32.
Addition of Maitake D-fraction reduces the effective dosage of vancomycin for the treatment of Listeria-infected mice.
Kodama N, Yamada M, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
Maitake D-fraction, beta1,6-glucan having beta1,3-branches, has been reported to activate the immune system of the host. To elucidate whether the D-fraction can reduce the clinical effective dosage of antibiotics in the treatment of opportunistic bacterial infection, we examined the effects of D-fraction on the treatment of Listeria monocytogenes-infected mice in combination with vancomycine (VCM), the only antibiotic used for methicillin-resistant Staphylococcus aureus (MRSA). Listeria-infection was introduced by its inoculation into the abdominal cavity of mice. Without treatment, all inoculated mice died within 3 days after the inoculation. In contrast, in the mice treated with combined therapy of D-faction (10 mg/kg per day) and VCM (10 mg/kg per day), the survival rate was maintained at 60% on the 10th day after the inoculation, which was superior to that of mice treated with VCM alone (10 mg/kg per day). To investigate the mechanism underlying the reinforcement of VCM treatment by the D-fraction, the activities of macrophages and splenic T cells of Listeria-infected mice were evaluated. In mice administered with both D-fraction and VCM, macrophages produced 2.7 times as much interleukin-1 as that of non-treated control mice. The bactericidal activity of splenic T cells was also enhanced by 2.6 times of that of non-treated control mice. These results indicate that D-fraction activates immuno-competent cells, induced cytokine production, and consequently enhanced the bactericidal activities of the splenic T cells against Listeria monocytogenes, suggesting the clinical benefit of D-fraction in the case of anti-bacterial treatment for patients with high risks.
21: Biosci Biotechnol Biochem. 2001 Sep;65(9):1993-2000.
Relationship between solubility of grifolan, a fungal 1,3-beta-D-glucan, and production of tumor necrosis factor by macrophages in vitro.
Ishibashi K, Miura NN, Adachi Y. Laboratory for Immunopharmacology for Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Grifolan, GRN, is a fungal antitumor beta-glucan isolated from Grifola frondosa. Various studies suggested that the underlying mechanism of the antitumor activity of GRN is strongly related to immune modulation. In the previous publication (Adachi et al., 1994; Okazaki et al., 1995), we have shown that GRN activates macrophages to produce tumor necrosis factor (TNF) in vitro. In this study, the structural unit essential to produce TNF was examined by chemical modifications of GRN. GRN suspended in distilled water was treated at 150 degrees C for up to 3 h. Addition of the resulting turbid solution to the RAW 264.7 macrophage-like cell line produced TNF, and the relative activity was diminished in relation to the heat treatment period. The fractions with a heating period longer than 15 min did not show any activity. After centrifugation of the resulting solution, significant activity was shown by precipitate fractions, suggesting that the insoluble form of GRN is important for TNF production. Interestingly, the precipitate fraction obtained from 9 min of treatment also had significant activity. In addition, admixing the soluble fraction with the particles significantly inhibited the TNF production. In contrast to these observations, the high-molecular-mass subfraction of the soluble fraction prepared by ultrafiltration produced significant amounts of TNF. Similar phenomena were shown with sodium hydroxide treatment and dimethylsulfoxide treatment. These facts strongly suggested that insoluble as well as a high molecular mass soluble form of GRN are required for TNF production by macrophages.
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22: Cancer Lett. 2001 Oct 30;172(2):193-8.
Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogenesis.
Matsui K, Kodama N, Nanba H. Department of Microbial chemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Japan. |
We have reported that D-Fraction extracted from maitake (Grifola frondosa), activates immune competent cells, and indicates anti-tumor activities. The D-Fraction was observed to induce angiogenesis in vivo and to enhance the proliferation capability and migration capability of human vascular endothelial cell in vitro. The D-Fraction also increased plasma vascular endothelial growth factor (VEGF) concentration significantly. Also VEGF and TNF-alpha production by the activated peritoneal macrophages were enhanced. These results suggest that the anti-tumor activity of the D-Fraction is not only associated with the activation of the immuno-competent cells but also possibly related to the carcinoma angiogenesis induction.
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23: Exp Biol Med (Maywood). 2001 Sep;226(8):758-65.
Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats.
Fukushima M, Ohashi T, Fujiwara Y. Department of Bioresource Science, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan. |
The effects of mushroom fibers on serum cholesterol and hepatic low-density lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a cholesterol-free diet with 50 g/kg cellulose powder (CP), 50 g/kg maitake (Grifola frondosa) fiber (MAF), 50 g/kg shiitake (Lentinus edodes) fiber (SF), or 50 g/kg enokitake (Flammulina velutipes) fiber (EF) for 4 weeks. There were no significant differences in the body weight, food intake, liver weight, cecum weight, and cecum pH among the groups. Cecal acetic acid, butyric acid, and total short-chain fatty acid (SCFA) concentrations in the SF and EF groups were significantly higher than those in the other groups. The serum total cholesterol concentration in the CP group was significantly higher than that in the MAF and EF groups. The very LDL (VLDL) + intermediate-density lipoprotein (IDL) + LDL-cholesterol concentration in the CP group was significantly higher than that in the MAF, SF, and EF groups, whereas the high-density lipoprotein (HDL)-cholesterol concentration in the EF group was significantly lower than that in the other groups at the end of the 4-week feeding period. The hepatic LDL receptor mRNA level in the EF group was significantly higher than that in the CP group. The fecal cholesterol excretion in the MAF, SF, and EF groups was significantly higher than that in the CP group. The results of this study demonstrate that MAF and EF lowered the serum total cholesterol level by enhancement of fecal cholesterol excretion, and in particular, by enhancement of hepatic LDL receptor mRNA in EF group.
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24: J Nutr Sci Vitaminol (Tokyo). 2001 Feb;47(1):57-63.
Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats.
Horio H, Ohtsuru M. Department of Food Science and Nutrition, Faculty of Home Economics, Nishikyushu University, Saga, Japan.
We have previously reported that rats with diabetes induced by injecting streptozotocin into neonates showed remarkably lower blood glucose, urine volume, and glucosuria after administration of Maitake (Grifola frondosa). In the present study, we investigated the effects of Maitake on insulin concentration, organ weight, serum composition, and islets of Langerhans in streptozotocin-induced diabetic rats using the same method. The diabetic rats were produced by injecting 80 mg/kg B.W. streptozotocin into 2-d-old neonates. From the age of 9 wk, the rats were given experimental diets for 100 d. The diabetes and control groups were given either diets containing 20% Maitake (DM and CM groups) or control diets (D and C groups). During administration of the experimental diets, we measured body weight, food intake, amount of feces, and serum insulin concentration at glucose loading. The glucose tolerance test was performed at the 10th week after the start of the experimental diets. The D group had an initial fasting blood glucose of 225+/-49 mg/dL, and a maximum blood glucose of 419+/-55 mg/dL at 60 min. In the DM group, however, the initial fasting blood glucose was 170+/-23 mg/dL, and the maximum blood glucose was 250+/-41 mg/dL at 15 min. Both values were markedly lower than those in the D group (p<0.05). The insulin concentration at 15 min. after glucose loading in the DM group was 41+/-16 microU/mL, which was significantly higher than that in the D group (15+/-7 microU/mL) (p<0.05). After the 100-d experimental period, blood samples were collected. The fructosamine level was significantly lower in the DM group (152+/-21 mmol/L) than in the D group (185+/-13 mmol/L). The concentration of 1.5-A.G. (1.5-anhydro glucitol) was significantly higher in the DM group (9.33+/-2.42 microg/mL) than in the D group (1.33+/-0.52 microg/mL). Observation of insulin antibody stain in the Langerhans cells of the pancreas using ABC method showed a decrease insulin antibody stain in the D group. The cells of the DM group were stained more darkly than those of the D group. From these results, we postulated that the bioactive substances present in Maitake can ameliorate the symptoms of diabetes.
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25: Altern Med Rev. 2001 Feb;6(1):48-60.
Maitake extracts and their therapeutic potential.
Mayell M.
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Maitake (Grifola frondosa) is the Japanese name for an edible fungus with a large fruiting body characterized by overlapping caps. It is a premier culinary as well as medicinal mushroom. Maitake is increasingly being recognized as a potent source of polysaccharide compounds with dramatic health-promoting potential. The most recent development is the MD-fraction, a proprietary maitake extract its Japanese inventors consider to be a notable advance upon the preceding D-fraction. The D-fraction, the MD-fraction, and other extracts, often in combination with whole maitake powder, have shown particular promise as immunomodulating agents, and as an adjunct to cancer and HIV therapy. They may also provide some benefit in the treatment of hyperlipidemia, hypertension, and hepatitis.
Publication Types:
• Review
• Review, Tutorial
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26: Jpn J Pharmacol. 2000 Nov;84(3):293-300.
Effects of maitake (Grifola frondosa) polysaccharide on collagen-induced arthritis in mice.
Shigesue K, Kodama N, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
We recently reported the anti-hepatitis effect of a polysaccharide, designated as the D-fraction, extracted from maitake. Its effect includes immuno-regulating activities. We investigated the effect of the glucan in collagen-induced arthritis (CIA). The D-fraction was administered to CIA mice for 30 consecutive days. Arthritis development was observed from the 4th day after the second immunization. The D-fraction did not have any influence on anti-type II collagen antibodies in blood serum or activated B cells. To determine how cellular immunity may be involved in the development of CIA, ratios of CD4+ T cells and their activated form in the axillary and inguinal lymph node T cells were detected by flow cytometry analysis. The ratios were not different between the D-fraction group and the control group. However, interleukin-1beta, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha productions from splenic macrophages were significantly increased to 2.0, 4.7 and 1.9 times the control group level, respectively. The ratio of macrophages in the whole spleen cells was 2.3 times that of the control group, and their migrating ability was 1.9 times higher. Based on these results, we concluded that the arthritis development induced by D-fraction administration is attributable to the activation of splenic macrophages.
27: Biosci Biotechnol Biochem. 2000 Sep;64(9):2001-4.
Suppression of D-galactosamine-induced liver injury by mushrooms in rats.
Lee EW, He P, Kawagishi H. Department of Applied Biochemistry, Faculty of Agriculture, Shizuoka University, Japan.
Six species of edible mushroom were found to suppress D-galactosamine-induced enhancement of plasma alanine and aspartate aminotransferase activities when powdered mushrooms were added to the diet (5%) and fed to rats for 2 wk. Grifola frondosa exhibited the most potent effect in a dose-dependent manner. A significant effect was observed only from the water-soluble low-molecular-weight fraction of G. frondosa. The results indicate that several mushrooms possess a protective effect against liver injury induced by D-galactosamine.
28: Mol Urol. 2000 Spring;4(1):7-13.
Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide).
Fullerton SA, Samadi AA, Tortorelis DG. Department of Urology, New York Medical College, Valhalla, New York, USA.
PURPOSE: To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro. MATERIALS AND METHODS: Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD. RESULTS: A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death. CONCLUSION: A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.
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29: Altern Med Rev. 2000 Feb;5(1):4-27.
The use of mushroom glucans and proteoglycans in cancer treatment.
Kidd PM.
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Immunoceuticals can be considered as substances having immunotherapeutic efficacy when taken orally. More than 50 mushroom species have yielded potential immunoceuticals that exhibit anticancer activity in vitro or in animal models and of these, six have been investigated in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but has shown early clinical promise. Maitake D-Fraction has limited proof of clinical efficacy to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor - PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide - have demonstrated the most promise. In Japanese trials since 1970, PSK significantly extended survival at five years or beyond in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and Phase III trials in China. In double-blind trials, PSP significantly extended five-year survival in esophageal cancer. PSP significantly improved quality of life, provided substantial pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic T-cells. Their extremely high tolerability, proven benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy makes them well suited for cancer management regimens.
Publication Types:
• Review
• Review, Tutorial
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30: J Nutr Sci Vitaminol (Tokyo). 1999 Jun;45(3):385-9.
Effect of maitake (Grifola frondosa) water extract on inhibition of adipocyte conversion of C3H10T1/2B2C1 cells.
Nakai R, Masui H, Horio H. Department of Food Science and Nutrition, School of Human Environmental Science, Mukogawa Women's University, Nishinomiya, Japan.
We investigated the effect of maitake (Grifola frondosa) water extract on inhibiting the conversion of C3H10T1/2B2C1 cells into adipocytes. Maitake water extract was fractionated by molecular sieve. Heat-labile compounds strongly inhibiting adipocyte conversion proved to occur in fractions of molecular weight of more than 10,000 on the basis of activity measurement of glycerol-3-phosphate dehydrogenase.
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31: Proc Soc Exp Biol Med. 1999 Sep;221(4):281-93.
Mushrooms, tumors, and immunity.
Borchers AT, Stern JS, Hackman RM. Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, California, USA.
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Medicinal properties have been attributed to mushrooms for thousands of years. Mushroom extracts are widely sold as nutritional supplements and touted as beneficial for health. Yet, there has not been a critical review attempting to integrate their nutraceutical potential with basic science. Relatively few studies are available on the biologic effects of mushroom consumption, and those have been performed exclusively in murine models. In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects. We believe that the antitumor mechanisms of several species of whole mushrooms as well as of polysaccharides isolated from Lentinus edodes, Schizophyllum commune, Grifola frondosa, and Sclerotinia sclerotiorum are mediated largely by T cells and macrophages. Despite the structural and functional similarities of these glucans, they differ in their effectiveness against specific tumors and in their ability to elicit various cellular responses, particularly cytokine expression and production. Unfortunately, our data base on the involvement of these important mediators is still rather limited, as are studies concerning the molecular mechanisms of the interactions of glucans with their target cells. As long as it remains unclear what receptors are involved in, and what downstream events are triggered by, the binding of these glucans to their target cells, it will be difficult to make further progress in understanding not only their antitumor mechanisms but also their other biological activities.
Publication Types:
• Review
• Review, Tutorial
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32: Biol Pharm Bull. 1998 Mar;21(3):278-83.
Activation of murine kupffer cells by administration with gel-forming (1-->3)-beta-D-glucan from Grifola frondosa.
Adachi Y, Ohno N, Yadomae T. Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
The effect of gel-forming (1-->3)-beta-D-glucan on the immunological activities of murine kupffer cells was examined. A branched type gel-forming (1-->3)-beta-D-glucan, GRN, was administered intravenously to mice. GRN associating to kupffer cells was detected by an immunohistochemical technique using anti-GRN antibody. A kinetic study of the activation of kupffer cells revealed that GRN could induce the enhanced production of cytokines and nitric oxide on 4 to 7 d after the administration. The activities are further augmented by adding GRN in the culture. The cytostatic activity of kupffer cells against murine lymphoma, EL-4, was also augmented by a time course similar to nitric oxide production. The cytostatic activity was reduced by adding an inhibitor of nitric oxide synthase, implying that the cytostatic activity of kupffer cells to EL-4 was dependent on nitric oxide. The administration of GRN increased the expression of CD11b, known as a beta-glucan receptor, on kupffer cells at day 7. The above data suggest that GRN could activate murine kupffer cells to enhance the production of cytokines and nitric oxide, and that the activation required 4 or 7 d, at least, after the administration with GRN.
33: Biol Pharm Bull. 1997 Jul;20(7):781-5.
Anti-hyperliposis effect of maitake fruit body (Grifola frondosa). I.
Kubo K, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
Experimental rat models (5-week-old Sprague-Dawley rats) with hyperlipemia were prepared by feeding high-cholesterol feed containing sodium cholate and casein as a protein source. Dried maitake (Grifola frondosa) powder was mixed with the basic high-cholesterol feed and the serum lipids were periodically measured. Values of cholesterol, triglyceride and phospholipid in serum of rats in the maitake-feed group were suppressed by 0.3-0.8 times those in animals fed the basic feed, the latter values being close to those in rats given normal feed. The value of high density lipoprotein (HDL)-cholesterol in serum which is generally reduced by the ingestion of high-cholesterol feed remained the level it was at the beginning of the experiment. Weights of extirpated liver and epididymal fat-pads were significantly less (0.6-0.7 times) than those in the basic feed group, indicating that maitake inhibits lipid accumulation in the body. Liver lipids were also measured and the values were found to be decreased by maitake administration as true of serum lipid, suggesting maitake has an anti-liver lipid activity. Measurement of the amount of total cholesterol and bile acid in feces showed, the ratio of cholesterol-excretion had increased 1.8 times and bile acid-excretion 3 fold by maitake treatment. From these results, it is believed that maitake helps to improve the lipid metabolism as it inhibits both liver lipid and serum lipid which are increased by the ingestion of high-fat feed.
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34: Immunopharmacol Immunotoxicol. 1997 May;19(2):175-83.
Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine.
Kurashige S, Akuzawa Y, Endo F. Department of Laboratory Sciences, Gunma University School of Health Sciences, Japan. |
ICR mice were treated with a carcinogen, N-butyl-N'-butanolnitrosoamine BBN), every day for 8 consecutive weeks and the effects of oral administration of edible mushrooms on the induction of urinary bladder carcinoma and on the activities of macrophages and lymphocytes were studied. Bladder carcinoma were found in all 10 mice (100%) treated with BBN alone, while we observed carcinoma only in 9 of 17 mice (52.9%), in 7 of 15 mice (46.7%) and 13 of 20 mice (65.0%) treated with Lentinus edodes, Grifola frondosa and Pleurotus ostreatus, respectively. Chemotactic activity of macrophages was suppressed in mice treated with BBN alone but maintained almost the normal level in mice treated with BBN plus Lentinus, Grifola or Pleurotus. Lymphocytes collected from mice treated with BBN plus each mushroom showed almost normal blastogenic response against concanavalin A, although those from mice treated with BBN alone completely retarded their response. Cytotoxic activity of lymphocytes against Yac-1 cells was also maintained at a normal level in mice treated with BBN plus each mushroom. Whereas in mice treated with BBN alone significant depression of NK cell activity occurred. Significantly higher cytotoxic activity against P-815 cells was observed in lymphocytes from mice treated with BBN plus each mushroom than that in lymphocytes from normal mice or mice treated with BBN alone.
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35: Nutr Rev. 1996 Nov;54(11 Pt 2):S91-3.
Functional properties of edible mushrooms.
Chang R. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.
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Edible mushrooms such as shiitake may have important salutary effects on health or even in treating disease. A mushroom characteristically contains many different bioactive compounds with diverse biological activity, and the content and bioactivity of these compounds depend on how the mushroom is prepared and consumed. It is estimated that approximately 50% of the annual 5 million metric tons of cultivated edible mushrooms contain functional "nutraceutical" or medicinal properties. In order of decreasing cultivated tonnage, Lentinus (shiitake), Pleurotus (oyster), Auricularia (mu-er), Flammulina (enokitake), Tremella (yin-er), Hericium, and Grifola (maitake) mushrooms have various degrees of immunomodulatory, lipid-lowering, antitumor, and other beneficial or therapeutic health effects without any significant toxicity. Although the data for this functional food class are not as strong as those for other functional foods such as cruciferous vegetables, because of their potential usefulness in preventing or treating serious health conditions such as cancer, acquired immune deficiency syndrome (AIDS), and hypercholesterolemia, functional mushrooms deserve further serious investigation. Additionally, there is a need for epidemiological evidence of the role of this functional food class.
Publication Types:
• Review
• Review, Tutorial
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36: Altern Ther Health Med. 1996 Sep;2(5):62-6.
The effect of maitake mushrooms on liver and serum lipids.
Kubo K, Nanba H. Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan.
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OBJECTIVE: To determine the efficacy of maitake mushrooms in inhibiting the elevation of liver and serum lipids in rats. DESIGN: Sprague-Dawley rats with hyperlipidemia were used to measure and compare the values of cholesterol, phospholipids, and triglycerides between cholesterol-fed rats and rats whose diets were fortified with 20% maitake mushroom dried powder. RESULTS: The values in maitake-fed rats were consistently less than those in the basic cholesterol-fed rats. The value of high-density lipoprotein cholesterol, which usually is decreased by taking high-cholesterol feed, maintained the level that it had at the beginning of the experiment. Weights of extirpated liver and epididymal fat pads were significantly less than those in the basic feed group. CONCLUSION: Our data suggest that maitake mushrooms have the ability to alter lipid metabolism by inhibiting both the accumulation of liver lipids and the elevation of serum lipids. Further studies are needed to elucidate the mechanism of activity of maitake mushrooms and to establish whether their action in humans is similar to that in the animal model tested here.
Publication Types:
• Clinical Trial
• Randomized Controlled Trial
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37: Biol Pharm Bull. 1996 Apr;19(4):608-12.
Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophage in mice.
Ohno N, Egawa Y, Hashimoto T. School of Pharmacy, Tokyo University Pharmacy and Life Science, Japan.
Nitric oxide (NO) is an important effector molecule on antimicrobial and antitumor effects of macrophages. (1 -> 3)-beta-D-Glucan (beta-glucan) is well known to show various immunopharmacological effects such as antimicrobial effect and antitumor effect by activating various points of host defense mechanisms. This paper deals with NO synthetic activity of peritoneal macrophage (PM) induced by beta-glucan administration in mice. The activity was determined by measuring NO concentration in PM culture by Griess reagent after 24 or 48 h in vitro culture. Administration (i.p. or i.v.) of a branched soluble (1 -> 3)-beta-D-glucan, grifolan (GRN), from Grifola frondosa enhanced NO synthesis of PM dose and time dependently. The activity was abrogated by the addition of N(G)-monomethyl-L-arginine (L-NMMA) in vitro. The most significant activity was observed at 3-7 d after the administration of GRN (250 mu g/mouse). PM from all strains of ICR, C3H/HeN, C3H/HeJ, BALB/c, BALB/c nu/nu, C57BL, and AKR mice showed significant activity by GRN administration. Among beta-glucans tested, SSG and OL-2, highly branched soluble glucans, and a particulate beta-glucan, zymosan, showed similar activity. Addition of GRN directly to in vitro RAW 264.7 or proteose peptone induced peritoneal macrophage (PP-PEC) culture could not enhance NO synthesis. However, NO synthesis of PP-PEC was enhanced in vitro by addition of GRN in the presence of interferon gamma (IFN gamma). Gene expression of IFN gamma mRNA in the liver and PEC were enhanced in GRN administered mice assessed by reverse transcriptase assisted PCR (RT-PCR) method. These facts strongly suggested that beta-glucan has capacity to enhance NO synthesis of PM in vivo through IFN gamma mediated mechanism.
38: Biol Pharm Bull. 1995 Oct;18(10):1320-7.
Structure-activity relationship of (1-->3)-beta-D-glucans in the induction of cytokine production from macrophages, in vitro.
Okazaki M, Adachi Y, Ohno N. Laboratory of Immunopharmacology of Microbial Products School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
In a previous study, we reported that one of the gel-forming (1-->3)-beta-D-glucans, grifolan (from Grifola frondosa, GRN), stimulated cytokine production from macrophages in vitro. However, several other gel-forming (1-->3)-beta-D-glucans, such as sonifilan (SPG) and SSG, did not induce cytokine production from macrophages. The ultrastructure of gel-forming (1-->3)-beta-D-glucans, especially the triple- and single-helix, does not affect the cytokine-inducing activity. The action on tumor necrosis factor alpha (TNF alpha) release was correlated with the molecular weight of GRN, since the highest molecular weight fraction of GRN, Mr > or = 45000, exhibited the strongest activity. Although, native SSG (Mr > or = 2000000) did not induce cytokine production, chemical modification involving debranching of the side chain glucosyl residues of SSG resulted in TNF alpha inducing activity. These results suggest that the branching ratio and molecular weight of (1-->3)-beta-D-glucans are important factors for the production of cytokines from macrophages. GRN-inducible TNF alpha release was reduced by co-culturing with SPG, SSG, or the soluble beta-glucan, laminarin (LAM). Pretreatment alone with SPG or LAM was not sufficient for significant inhibition of GRN-inducible TNF alpha release. TNF alpha production induced with 50 micrograms/ml of zymosan (ZyM) was also reduced by addition of SPG, but TNF alpha production, stimulated with a higher concentration (100 micrograms/ml) of ZyM or with lipopolysaccharide (LPS), was not reduced significantly. The inhibitory effect of LAM on the uptake of GRN by RAW264.7 cells was not completely correlated with TNF alpha release. These results suggest that macrophages may incorporate beta-glucans through certain (1-->3)-beta-D-glucan-specific mechanisms and/or other endocytosis pathways, and that the beta-glucan-specific route is partially associated with cytokine production. In conclusion, TNF alpha release by macrophages is induced only by beta-glucans with high molecular weights and lower branching ratios, and the mechanism for the recognition of beta-glucans is multiple and assumed to be divided into several parts involving various cellular functions.
39: Biol Pharm Bull. 1995 Jan;18(1):126-33.
Enhancement of LPS triggered TNF-alpha (tumor necrosis factor-alpha) production by (1-->3)-beta-D-glucans in mice.
Ohno N, Asada N, Adachi Y. Tokyo College of Pharmacy, Japan.
Effects of (1-->3)-beta-D-glucans on tumor necrosis factor-alpha (TNF-alpha) production in mice in vivo were investigated with or without triggering stimulation of lipopolysaccharide (LPS). Administration of grifolan (GRN) (100-250 micrograms/mouse) obtained from Grifola frondosa, did not elevate the TNF-alpha concentration in serum, but significantly elevated LPS (10 micrograms/mouse)-elicited TNF-alpha production in serum. The priming effect was observed as early as 2 h after administration and remained high for 3 weeks. The priming effect was dependent on the strain of mice, i.e. ICR, BALB/c, and MRL/lpr (15 weeks old) showed high response. In addition, GRN administration increased membrane-bound TNF-alpha assessed by Western blotting and flow cytometry. Comparing the activity using structurally related glucans obtained from other microorganisms, highly branched glucans, SSG isolated from Sclerotinia sclerotiorum IFO 9395 and OL-2 from Omphalia lapidescence significantly increased TNF-alpha production. Small molecular weight GRN derivatives prepared by heat degradation method showed weaker priming effect. These facts suggested that the glucans showed priming effect of TNF-alpha production in vivo and that this effect was related to the degree of branching and molecular weight.
40: Biol Pharm Bull. 1994 Dec;17(12):1554-60.
Enhancement of cytokine production by macrophages stimulated with (1-->3)-beta-D-glucan, grifolan (GRN), isolated from Grifola frondosa.
Adachi Y, Okazaki M, Ohno N. Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science, Japan.
The ability of grifolan (GRN), a purified fungal (1-->3)-beta-D-glucan, to induce various cytokines from macrophages was examined in vitro. Interleukin-6 (IL-6) activity in supernatants from the culture of macrophage cell line, RAW264.7 was dependent on increasing doses of GRN. The level of IL-6 induced with 500 micrograms/ml of GRN was comparable to that induced with lipopolysaccharide (LPS) 10 micrograms/ml. Enhancement of the mRNA level of IL-6 by treatment with GRN was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of GRN on production of IL-6 was also observed using peritoneal macrophages from C3H/HeJ mice which did not respond to endotoxins. This data suggested that the ability of GRN to activate IL-6 production of macrophages is not due to contamination of endotoxins in the preparation. Enhanced production of cytokine by GRN was observed not only with IL-6, but also with interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). In the production of TNF alpha, GRN was more effective than LPS used in this study. Other soluble or gel-forming(1-->3)-beta-D-glucans from various sources did not enhance the production of such cytokines although they are structurally similar to GRN. The above results indicate that GRN is a novel macrophage activator which augments cytokine production without dependence on endotoxins.
41: Biol Pharm Bull. 1994 Aug;17(8):1106-10.
Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). I.
Kubo K, Aoki H, Nanba H. Yukiguni Maitake Co., Ltd. Niigata, Japan.
The fruit body of Grifola frondosa (maitake), Basidiomycetes was confirmed to contain substances with anti-diabetic activity. When 1 g/d of powdered fruit body of maitake was given orally to a genetically diabetic mouse (KK-Ay), blood glucose reduction was observed, in contrast to the control group in which the blood glucose increased with ageing. Moreover, levels of insulin and triglyceride in plasma demonstrated a change similar to blood glucose with feeding of maitake. Ether-ethanol-soluble (ES) and hot water-soluble (WS) fractions were prepared from the fruit body and their hypoglycemic activity was examined. Blood glucose-lowering activity was found when ES-fraction or WS-50% ethanol float (X) fraction was administered orally, but other WS-fractions were inactive. These results suggest that the anti-diabetic activity was present not only in the ES-fraction consisting of lipid but also in the X-fraction of peptidoglycan (sugar:protein = 65:35).
42: Zhonghua Wai Ke Za Zhi. 1994 Jul;32(7):433-4.
Prophylactic effects of zhuling and BCG on postoperative recurrence of bladder cancer
Yang DA, Li SQ, Li XT. General Hospital of Jinan Unit of People's Liberation Army. PR China.
The prophylactic effects of Chinese herbal medicine Zhuling (Grifola umbellata pilat) and BCG on bladder cancer after TURBT and partial cystectomy were evaluated. 146 patients with bladder cancer were divided into 3 groups, Zhuling, BCG, and control group. Follow-up for 48-124 months (average 70.8 months) showed that the tumor recurrence rate was 33.3%, 34.3% and 65.1%, respectively. Compared to the control group, the recurrence rate of Zhuling group and BCG group was significantly decreased (P < 0.01). The effect of Zhuling was similar to that intravesical BCG. Zhuling was cheaper and convenient in usage, and no side effects.
Publication Types:
• Clinical Trial
• Controlled Clinical Trial
43: Zhonghua Yu Fang Yi Xue Za Zhi. 1994 May;28(3):147-50.
Inhibitory effects of fifteen kinds of Chinese herbal drugs, vegetables and chemicals on SOS response
Jin ZC, Qian J. Department of Pathophysiology, Zhejiang Medical University, Hangzhou.
Effects of 15 kinds of herbal drugs, vegetables and chemicals on lex-dependent sfi-SOS response were determined by micropersistent and/or pulse models induced by 4-Nitroquinoline-N-oxide (4NQO) and Mitomycin C (MMC) in Escherichia coli(E. coli) PQ37 and PQ35, respectively. Results showed the water extract of Rhizoma Polygonati (RP), Fructus Chebulae (FC), Radix Polygoni Multiflori (RPM), Fructus Ligustri Lucidi (FLL), Bulbus Fritillariae Thunbergii (BFT), shell of water chestnut with a pedicle, Chinese chives juice, and solutions of 5-Fluorouracil, Tannic acid and garlicin could inhibit SOS responses with a dose-response relationship and suggested the inhibitory effects took place both inside and outside E. coli cells. Water extract of FC, FLL, BFT, shell of water chestnut with a pedicle, Chinese chives juice and solution of 5-Fluorouracil and Tannic acid could intracellularly inhibit SOS responses induced by MMC in E. coli PQ35, and acetone extract of Grifola Frondosa (GF) could extracellularly inhibit SOS responses in E. coli PQ37 and intracellularly in PQ35 induced by 4NQO or MMC. Water extract of raw hawthorn. Radix Angelicae Duhuricae (RAD), Radix Ophiopogonis (RO), and 5-Fluorodeoxyuridine could extracellularly inhibit SOS responses induced by 4NQO in E coli PQ37. The possible mechanisms of intracellular inhibition and antidamage repair were discussed in the paper.
44: Zhonghua Wai Ke Za Zhi. 1991 Jun;29(6):393-5, 399.
Inhibitory effect of Chinese herb medicine zhuling on urinary bladder cancer. An experimental and clinical study
Yang DA. General Hospital of Jian Unit of People's Liberation Army. PR China.
Inhibitory effect of Zhuling (Grifola umbellata pilat) on urinary bladder cancer was determined experimentally and clinically. The results showed that zhuling inhibited significantly the induction of bladder cancer in rats exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), decreasing from 100% (18/18) in control group to 61.1% (11/18) in zhuling (P less than 0.01). Zhuling was given to 22 patients with recurrent bladder cancer after TUR or partial cystectomy. The patients were followed up for 12 to 38 months (average 26.5 months). Bladder cancer recurred in seven of the patients with a longer recurrence interval (19.2 months) after medication than before medication (P less than 0.05). The remaining 15 patients had no recurrence. The mechanism of Zhuling is discussed.
45: Chem Pharm Bull (Tokyo). 1989 Jul;37(7):1838-43.
Physiochemical properties and antitumor activities of chemically modified derivatives of antitumor glucan "grifolan LE" from Grifola frondosa.
Adachi Y, Ohno N, Ohsawa M, Sato K, Oikawa S, Yadomae T.
Antitumor glucan, grifolan LE (GRN LE), from Grifola frondosa was chemically modified to examine the structure-function relationship of the products. Modification by periodate, borohydride and acid hydrolysis of side chains of GRN LE did not alter properties such as helical conformation and antitumor activity of GRN LE. Introduction of carboxylic acid groups into the side chains by oxidation with periodate and with sodium chlorite (GRN LE-PC), and substitution with carboxymethyl (CM) or hydroxyethyl (HE) groups abolished the gel-forming ability of GRN LE. Significant antitumor activity was observed in all of the derivtives having gel-forming ability as well as some derivatives having no such ability. These results suggested that essential factors required for antitumor activity were (1----3)-beta-D-glucosyl linkages and high molecular weight, and that accessory groups could be linked to the main chain without loss of antitumor activity in a higher ratio than that of gel-forming ability.
46: Chem Pharm Bull (Tokyo). 1989 Feb;37(2):410-3.
Antitumor and immunomodulating activities of a beta-glucan obtained from liquid-cultured Grifola frondosa.
Suzuki I, Hashimoto K, Oikawa S, Sato K, Osawa M, Yadomae T.
The effects of the beta-1,3-glucan, LELFD, obtained from liquid-cultured mycelium of Grifola frondosa, on the growth of syngeneic tumors and immune responses in mice were examined. In Meth A or IMC solid tumor systems, LELFD administered intraperitoneally (i.p.) or intralesionally (i.l.) exhibited significant antitumor effects. However, the growth of L1210 and P388 leukemias was unaffected by the injection of LELFD. The injection of LELFD i.p. enhanced the activities of natural killer cells and macrophages in mice. LELFD also enhanced the antibody response when it was injected i.p. with sheep red blood cells into mice. Furthermore, it was found that LELFD could activate the alternative complement pathway.
47: J Nutr Sci Vitaminol (Tokyo). 1989 Feb;35(1):91-4.
Dietary mushrooms reduce blood pressure in spontaneously hypertensive rats (SHR).
Kabir Y, Kimura S. Department of Food Chemistry, Faculty of Agriculture, Tohoku University, Sendai, Japan.
The blood pressure of spontaneously hypertensive rats (SHR) were significantly reduced by Maitake feeding for 8 weeks period beginning at a time when the animals were 10 weeks of age with well-established high blood pressure. There was no difference in the plasma total and free cholesterol, triglyceride and phospholipid levels between the Maitake fed animals and the control. On the other hand, Shiitake mushroom did not reduce the blood pressure, but significantly lower the plasma free cholesterol, triglyceride and phospholipid in compared with the control. The results suggest that dietary Maitake mushroom reduce the blood pressure.
48: J Pharmacobiodyn. 1987 Nov;10(11):644-51.
Host-mediated antitumor effect of grifolan NMF-5N, a polysaccharide obtained from Grifola frondosa.
Takeyama T, Suzuki I, Ohno N. Tokyo College of Pharmacy, Japan.
The antitumor mechanism of grifolan NMF-5N, a beta-1,3-glucan obtained from mycelia of Grifola frondosa, was examined. Grifolan NMF-5N did not show direct cytocidal effect on cultured tumor cells. However, intraperitoneal injection of grifolan NMF-5N increased the number of peritoneal exudate cells and peritoneal adherent cells which showed cytostatic activity towards syngeneic tumor cells. In an in vivo assay, the administration of carrageenan, an inhibitor of macrophage function, reduced the antitumor activity of grifolan NMF-5N. The delayed-type hypersensitivity reaction was augmented in the grifolan NMF-5N-administered mice. The administration of NMF-5N augmented the induction of cytotoxic T cells but the antitumor activity of grifolan NMF-5N was reduced in athymic nu/nu mice. In addition, the treatment with anti-Thy 1,2 antibody and complement C' of spleen cells taken from mice which showed regression of tumor due to grifolan NMF-5N, reduced the neutralizing effect in Winn assay. These results suggested that grifolan NMF-5N shows antitumor activity via host-mediated mechanisms and both macrophages and T cells play important roles in the mechanisms.
49: J Nutr Sci Vitaminol (Tokyo). 1987 Oct;33(5):341-6.
Effect of shiitake (Lentinus edodes) and maitake (Grifola frondosa) mushrooms on blood pressure and plasma lipids of spontaneously hypertensive rats.
Kabir Y, Yamaguchi M, Kimura S. Department of Food Chemistry, Faculty of Agriculture, Tohoku University, Sendai, Japan.
To study the effect of Shiitake (Lentinus edodes) and Maitake (Grifola frondosa) on hypertension, spontaneously hypertensive rats (SHR) were fed a diet containing 5% mushroom powder and 0.5% NaCl solution as drinking water for 9 weeks. The dietary mushrooms decreased the blood pressure. The plasma free cholesterol level decreased in Shiitake-fed animals, whereas in Maitake-fed animals the total cholesterol level decreased. There was no difference in the plasma triglyceride and phospholipid levels among the experimental groups. Shiitake feeding resulted in a decrease in VLDL- and HDL-cholesterol whereas Maitake feeding caused a decrease in VLDL-cholesterol only. Plasma LDL-cholesterol was not affected by dietary mushrooms. The results suggest that dietary mushrooms prevent blood pressure increase in hypertension.
50: J Pharmacobiodyn. 1987 Feb;10(2):72-7.
Antitumor effect of polysaccharide grifolan NMF-5N on syngeneic tumor in mice.
Suzuki I, Takeyama T, Ohno N, Oikawa S, Sato K, Suzuki Y, Yadomae T.
Antitumor activity of grifolan NMF-5N, a beta-1,3-glucan obtained from mycelia of Grifola frondosa, was examined. Grifolan NMF-5N showed antitumor activities in allogeneic and syngeneic murine tumor systems. In the allogeneic tumor system, a potent antitumor activity over 95% was observed against the solid form of sarcoma 180 when grifolan NMF-5N was injected intraperitoneally (i.p.) at 25-200 micrograms/mouse daily for 10 successive days. In the syngeneic tumor systems, significant antitumor activities were observed against Meth A fibrosarcoma and MM 46 carcinoma by injection at 100 micrograms/mouse daily for 5 successive days, especially i.p. injection at day 7-11, when the tumor cells were inoculated subcutaneously (s.c.) on day 0. Moreover, when grifolan NMF-5N was injected i.p. every other week, significant antitumor activity was also observed. In addition, a single treatment with grifolan NMF-5N at 500 micrograms/mouse showed antitumor activities. Grifolan NMF-5N exhibited antitumor activities against these two syngeneic tumors by intraveneous (i.v.) injection. However, a marked inhibitory activity was observed by intratumorous (i.t.) injection against Meth A fibrosarcoma but not against MM46 carcinoma. These results suggest that antitumor activities of grifolan NMF-5N in murine syngeneic tumor systems depend on not only dosage but also injection routes and timing.
51: J Pharmacobiodyn. 1986 Oct;9(10):861-4.
Antitumor activity of a beta-1,3-glucan obtained from liquid cultured mycelium of Grifola frondosa.
Ohno N, Adachi Y, Suzuki I, Oikawa S, Sato K, Ohsawa M, Yadomae T.
The antitumor activity of a branched beta-1,3-glucan "grifolan LE" purified from liquid cultures of Grifola frondosa (Ohno et al. Chem. Pharm. Bull., 34, 1709-1715 (1986] was examined on an allogeneic murine tumor system. By intraperitoneal (i.p.) administration (100-200 micrograms/mouse/d X 5) at days 1 to 9 from the tumor transplantation, grifolan LE showed marked inhibitory activity on the growth of solid form sarcoma 180 in ICR mice. Significant activity was also observed in intravenous (i.v.) or intratumoral (i.t.) administrations. However, the oral (p.o.) administration of grifolan LE was not effective. I.p. administration of grifolan LE at a dose of 100 micrograms/mouse/d X 5 before the tumor transplantation showed significant inhibition of tumor growth. I.p. administration of grifolan LE at day +11 to +19 was also effective. Grifolan LE was not effective on the ascites form of sarcoma 180. The pretreatment of sarcoma 180 cell with grifolan LE in vitro did not affect tumor growth. The mice cured from the solid form of sarcoma 180 by administration of grifolan LE had the ability to reject the same tumor cell. From these results, it is suggested that the antitumor activity of grifolan LE occurred by modification of biological responses.
52: J Pharmacobiodyn. 1985 Mar;8(3):217-26.
Effect of a polysaccharide fraction from Grifola frondosa on immune response in mice.
Suzuki I, Itani T, Ohno N, Oikawa S, Sato K, Miyazaki T, Yadomae T.
The biological and immunomodulating activities of polysaccharide fraction (GF-1), an antitumor poysaccharide fraction from cultured fruiting bodies of Grifola frondosa, was examined in mice. GF-1 showed no cytocidal effect on culturing tumor cells. However, GF-1 induced resistance against Sarcoma 180 in ICR mice which had completely regressed from the tumor by the effect of GF-1. The administration of GF-1 into mice increased the weights or cell numbers of spleen, and peritoneal cavity. GF-1 enhanced the antigen specific antibody response and carbon clearance activity, whereas GF-1 did not show polyclonal B cell activation and mitogenic activities, and the effect on delayed type hypersensitivity.
53: J Pharmacobiodyn. 1984 Jul;7(7):492-500.
Antitumor activity of a polysaccharide fraction extracted from cultured fruiting bodies of Grifola frondosa.
Suzuki I, Itani T, Ohno N, Oikawa S, Sato K, Miyazaki T, Yadomae T.
Antitumor activity of a polysaccharide fraction (GF-1) extracted from cultured fruiting bodies of a fungus, Grifola frondosa, was examined on allogeneic and syngeneic tumors in mice. GF-1 had a marked inhibitory activity against the growth of subcutaneously (s.c.) inoculated Sarcoma 180 by the intraperitoneally (i.p.) injection at 0.5-5.0 mg/mouse for 10 successive days. A significant antitumor activity was also observed when GF-1 at 4.0 mg/mouse was i.p. injected successively on days +1-+5, +7-+11, +14-+18 or +21-+25 if the tumor cells were inoculated s.c. on day 0. Similar results were obtained by a single i.p. injection of GF-1 at 2.0 mg/mouse on day +1, +7, +14 or +21. When GF-1 was injected i.p., intravenously (i.v.) or intratumorally (i.t.), all of them showed an equivalent level of higher inhibitory activity (inhibition ratio; over 90%). However, the oral (p.o.) administration was not effective. The pretreatment of mice with GF-1 at 2.0 or 4.0 mg/mouse for 5 times before tumor inoculation did not show a significant antitumor activity. In addition, GF-1 administered i.p. at varying times before and/or after the tumor inoculation showed no antitumor activity against ascites form of Sarcoma 180. In the syngeneic systems, GF-1 exhibited an antitumor activity against solid form of Meth A fibrosarcoma in BALB/c mice and MM46 carcinoma in C3H/He mice.
53: Nippon Yakurigaku Zasshi. 1976;72(1):77-94.
Studies on antitumor activities of Basidiomycetes-antitumor activity of polysaccharides and sex factors
Ito H, Naruse S, Sugiura M.
We have already reported antitumor activities of fungal and bacterial polysaccharides on mice. In the present experiment, the influence of the sex on antitumor effects on such material from Grifola umbellata, Coriolus versicolor Fries or Sargassum thumbergii and the immunity of mice against tumor were investigated. The growth velocities of Sarcoma 180, Ehrlich solid carcinoma, Pulmonary tumor 7423 and MF-sarcoma bearing mice both without treatment and those treated with polysaccharides were more rapid in males than in females. The regression rates in mice with the above tumors were higher in females than in males. However, a few DS Mie mice with Sarcoma 180 and A/Jax Mie mice with Ehrlich solid carcinoma regressed spontaneously. The growth velocity of Shionogi carcinoma 42 was not influenced by the sex. On other hand, both males and females which had experienced a regression of ascites tumor after the administration of polysaccharides rejected the re-implanted Ehrlich ascites carcinoma, Sarcoma 180, NF-sarcomma and Shionogi carcinoma 42. These results suggest that a strong ehancement of immune response occurs in the tumor implanted in the host animal by the administration of polysacchrides. The combination of X-ray irradiation Ehrlich ascites cells and polysacchrides strengthens the antitumor effect of NF-sarcoma and Shionogi carcinoma 42. Peritoneal exudate cells and lymphocytes were compared between the male and female mice after being treated with ATSO and P.GU-1. Such cells were present to a much greater extent in females.
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