ALOE VERA, Sábila

Plantas que actúan sobre el eje de Inteligencia Biológica

ENGLISH

ALOE VERA

(Sábila)

Desde tiempos remotos el Aloe vera ha sido utilizado para curar diversas afecciones de piel, cabello y aparatos gastrointestinal y resp

iratorio con excelentes resultados. Su utilización se remonta al siglo I DC, con Dioscórides, quien describió sus virtudes medicinales y cosméticas en su herbolaria griega.

Los chinos fueron los primeros en utilizar el Aloe vera. También fue utilizado por Cleopatra en el antiguo Egipto, así como los romanos, griegos, hindúes, árabes y otros pueblos que se beneficiaron de su uso medicinal. En España y otros países de la ribera del mediterráneo, el Aloe era esencial en la medicina popular, hasta que su uso generalizado en la farmacia moderna lo dejó en el olvido como a otras plantas medicinales. Al finalizar la segunda guerra mundial se redescubrió el poder terapéutico de la planta al comprobar que los habitantes de Hiroshima y Nagasaki, quienes padecieron graves quemaduras, una vez tratados con aloe, se curaban más rápidamente y en muchos casos sin cicatrices.

En muchos sitios se le ha considerado como planta protectora y portadora de buena suerte.

PRESIONE LA BOTELLA PARA CONOCER LA PLANTA

Características botánicas:

Nombre botánico: Aloe vera, pertenece a la familia de las Aloeaceae. Es originaria del sur de África. En la mayoría de formularios y libros de referencia, Aloe barbadensis Mill. Es el nombre correcto de la especie y Aloe vera (L.) Burm. f. se considera un sinónimo. Sin embargo, según las Reglas Internacionales de Nomenclatura Botánica, Aloe vera (L.) Burm. f. es el nombre legítimo de esta especie.

Nombres populares: Aloe capensis, aloe curacao, aloe vera, aloes, aloès, aloès du Cape, aloès fèroce, aloes vrai, aloès vulgaire, alovis, Barbados aloe, Bergaalwyn, Bitteraalwyn, Cape aloe, chirukattali, Curacao aloe, Curacao alos, Echte Aloe, ghai kunwar, gheekuar, ghikanvar, ghikuar, ghikumar, ghikumari, ghikwar, ghiu kumari, ghrita kumari, ghritakumari, grahakanya, gwar-patha, haang takhe, hlaba, Indian aloe, jadam, korphad, kumari, kumaro, kunvar pata, kunwar, laloi, laluwe, lo-hoei, lo-hoi, lou-houey, lu wei, luchuy, manjikattali, Mediterranean aloe, murr sbarr, musabar, rokai, sabbara, saber, sábila, sabilla, sabr, saibr, savila, savilla, semper vivum, shubiri, sibr, siang-tan, star cactus, tuna, umhlaba, waan haang charakhe, wan-hangchorakhe, yaa dam, yadam, zábila, zambila

Descripción: es una planta de hojas carnosas y puntiagudas, de color verde claro cuando no recibe mucho sol y de color terroso cuando recibe mucho sol y poco agua. Las hojas miden 30–50 cm de longitud y 10 cm de ancho en la base. La planta mide aproximadamente 60 cm. cuando es adulta y es muy resistente a las plagas y a la falta de agua. Cuando se hace un corte en la hoja de la planta, segrega un líquido amarillento verdoso, entre la pulpa y la piel, llamado “Server”(Savia) que también se utiliza con fines medicinales y es de color desagradable y gusto amargo.

Distribución geográfica: Nativa del este y del sur de Afríca, posteriormente fue introducida al norte de Afríca, península arábica, China, Gibraltar, países mediterráneos y las indias occidentales. Actualmente se cultiva en Aruba, Bonaire, Haiti, India, Sudáfrica, EEUU y Venezuela.

Principios activos:

De esta planta se pueden utilizar dos partes:

1. El jugo solidificado de las células del periciclo y zonas adyacentes del parénquima de la hoja, que fluyen espontáneamente al cortar la hoja que luego se secan. Esta parte de la hoja contiene drivados hidroxiantraquinónicos: Aloínas A y B (aloína, barbaloína), aloerresinas A, B y C (glucosilcromonas). Estos principios activos se encuentran en el canal sub-epidérmico de las hojas de Aloe, y se observan como un líquido amarillento, denominado Aloína. Producen un efecto laxante, más o menos intenso según la dosis. Tras administración oral, los derivados hidroxiantracénicos son transformados por la flora intestinal en aloe-emodín antrona, que actúa específicamente a nivel de colon sobre las terminaciones nerviosas de la pared del colon. Por un lado, estimulando el peristaltismo del intestino grueso, por el otro, estimulan la secreción mucosa y de líquido hacia la luz intestinal, al mismo tiempo que inhiben la reabsorción de agua y electrolitos en el colon.

2. Fracción mucilaginosa incolora del parénquima o pulpa de las hojas de A. barbadensis (gel de áloe vera). Contiene mayoritariamente agua y abundantes polisacáridos, como: glucomananos, glucogalactomananos, galactoglucoarabinomananos y mananos acetilados. Entre ellos, sobresalen como componentes activos importantes el acemanano, mezcla de polisacáridos complejos de tipo beta-(1-4)-manano O-acetilados, y el aloérido, polisacárido de elevado peso molecular constituido por glucosa, galactosa, manosa y arabinosa.

Nuestro producto consiste en cápsulas de gel de Aloe vera que solo contienen mucílagos de polisacáridos. Por lo tanto, sus indicaciones no incluyen los efectos catárticos causados por las antraquinonas, ya que no contiene estos principios.

Acción Farmacológica:

La acción sinérgica de los diversos principios activos contenidos en el gel de aloe ofrece acción cicatrizante y regeneradora celular, antiinflamatoria, inmunoduladora, bactericida y antiviral. El acemanano y, más recientemente, el aloérido se han descrito como los principales responsables de la acción inmunomoduladora.

En las alergias, neutraliza los efectos de las reacciones inmunes y también en el asma, promoviendo la eliminación de secreciones del tracto respiratorio.

Ofrecen también efectos protectores y de regeneración de las mucosas del tracto gastrointestinal y neutraliza la acidez gástrica, por lo que se utilizan en la enfermedad ulceropéptica gastroduodenal y en las enfermedades inflamatorias crónicas del tracto gastrointestinal.

Debido a su contenido en mucílagos posee propiedades hidratantes y emolientes, de utilidad no sólo en terapéutica sino también en cosmética.

Indicaciones

1) Dermatológicas: Regenerador celular, cicatrizante, tonificador y de alta penetración en la piel. Estimula la reproducción de nuevas células. Es un excelente filtro solar de rayos ultravioleta y elimina las manchas causadas por el sol, cuando se utiliza por tiempo prolongado. Previene las estrías, se utiliza como champú y acondicionador para tratar enfermedades del cuero cabelludo (caspa, grasa, psoriasis); también para la gingivitis, herpes labial, aftas, odontalgias y previene las caries. Se usa en quemaduras (químicas, solares, etc), porque calma el dolor, evita la posibilidad de infecciones y regenera las células. También sirve como tratamiento para las hemorroides, cicatrices, várices, acné, picaduras por insectos, ligeramente laxante, se utiliza para el cáncer de piel. También en eczemas y psoriasis.

2) Enfermedades gastrointestinales crónicas: úlceras, gastritis, rectocolitis, ileitis, hemorroides.

3) Enfermedades respiratorias: Asma bronquial, bronquitis crónica, enfermedad broncopulmonar obstructiva crónica

Medicina Sistémica y Aloe Vera

Contraindicaciones:

Gel de áloe: Alergia conocida a plantas de la familia de las Aloeaceae.

Efectos Secundarios:

Prácticamente no existen referencias sobre efectos adversos del gel de áloe. Ocasionalmente, se ha descrito algún caso de dermatitis o reacción alérgica.

Toxicidad:

No tiene ninguna toxicidad

Posología:

Recomendamos ingerir el contenido de 2 cápsulas con cada comida.

Referencias

1: Int Immunopharmacol. 2001 Jul;1(7):1275-84.

Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.

Lee JK, Lee MK, Yun YP. College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.

Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.

2: Int J Immunopharmacol. 2000 May;22(5):365-72.

In vivo macrophage activation in chickens with Acemannan, a complex carbohydrate extracted from Aloe vera.

Djeraba A, Quere P. INRA, Virologie Aviaire et Oncologie, Nouzilly, France.

Acemannan (ACM 1), a beta-(1,4) -acetylated mannan isolated from Aloe vera, can be used as an effective adjuvant in vaccination against some avian viral diseases. Our results demonstrate a quick and lasting in vivo priming effect of ACM 1 on macrophage response after intramuscular inoculation in chickens (500 microg per 2-month-old bird). In response to IFN-gamma in vitro, monocytes from ACM 1-treated chickens exhibited a strong enhancement of NO production from 3 to 9 days p.i., but a weaker effect on MHC II cell surface antigen expression on day 3 p.i. A stimulating effect of ACM 1 treatment was also observed on spontaneous and inducible NO production for splenocytes only on day 3 p.i. By that time, splenocytes exhibited a strong higher capacity to proliferate in response to the T cell-mitogen PHA. At the same time, the in vivo capacity to produce NO, measured by the (NO(-)(2)+NO(-)(3)) serum level after intravenous LPS injection, increased greatly from 3 to 9 days p.i. In conclusion, ACM 1 was able efficiently and durably to increase the activation capacity of macrophages from the systemic immune compartment (in particular from the blood and spleen after an intramuscular injection) in chickens, especially for NO production. These findings provide a better understanding of the adjuvant activity of ACM 1 for viral and tumoral diseases.

3: Mol Pharmacol. 1998 Mar;53(3):415-21.

Induction of apoptosis in a macrophage cell line RAW 264.7 by acemannan, a beta-(1,4)-acetylated mannan.

Ramamoorthy L, Tizard IR. Department of Veterinary Pathobiology, Texas A & M University , College Station , Texas , USA .

Acemannan is a polydispersed beta-(1,4)-linked acetylated mannan with antiviral properties. It is an immunomodulator, and studies in our laboratory have shown that it causes activation of macrophages. In the presence of IFNgamma, acemannan induced apoptosis in RAW 264. 7 cells. These cells exhibited chromatin condensation, DNA fragmentation, and laddering characteristic of apoptosis. The induction of apoptosis by acemannan and IFNgamma does not seem to be mediated by nitric oxide, since N-nitro-L-arginine methyl ester, the nitric oxide inhibitor, had no effect. Acemannan in the presence of IFNgamma also inhibited the expression of bcl-2. These results suggest that acemannan in the presence of IFNgamma induces apoptosis in RAW 264.7 cells through a mechanism involving the inhibition of bcl-2 expression.

4: Int J Immunopharmacol. 1997 Feb;19(2):75-82.

Upregulation of phagocytosis and candidicidal activity of macrophages exposed to the immunostimulant acemannan.

Stuart RW, Lefkowitz DL, Lincoln JA, Howard K, Gelderman MP, Lefkowitz SS.
Department of Biological Sciences, Texas Tech University, Lubbock 79409, U.S.A.

Previous studies by these investigators have shown that mannosylated bovine serum albumin (m-BSA) enhances the respiratory burst (RB), phagocytosis, and killing of Candida albicans by resident murine peritoneal macrophages (MO). Upregulation of the above MO functions was associated with binding of m-BSA to the MO-mannose receptor. The present study was done to determine if the immunostimulant, acemannan prepared from aloe vera, could stimulate MO in a similar manner. Resident peritoneal MO collected from C57BL/6 mice were exposed to acemannan for 10 min. The RB was measured using chemiluminescence and demonstrated approximately a two-fold increase above the media controls. In studies involving phagocytosis, MO were exposed to acemannan, washed and exposed to Candida at a ratio of 1:5. The percent phagocytosis and Candida killing were determined using fluorescence microscopy. There was a marked increase in phagocytosis in the treated cultures (45%) compared to controls (25%). Macrophages exposed to acemannan for 10 min resulted in ca 38% killing of Candida albicans compared with 0-5% killing in controls. If MO were incubated with acemannan for 60 min, 98% of the yeast were killed compared to 0-5% in the controls. The results of the present study indicate that short term exposure of MO to acemannan upregulates the RB, phagocytosis and candidicidal activity. Further studies are needed to clarify the potential use of this immunostimulant as an anti-fungal agent.

5: Immunopharmacology. 1996 Nov;35(2):119-28.

Activation of a mouse macrophage cell line by acemannan: the major carbohydrate fraction from Aloe vera gel.

Zhang L, Tizard IR. Department of Veterinary Pathobiology, Texas A & M University College Station 77843, USA .

Acemannan is the name given to the major carbohydrate fraction obtained from the gel of the Aloe vera leaf. It has been claimed to have several important therapeutic properties including acceleration of wound healing, immune stimulation, anti-cancer and anti-viral effects. However, the biological mechanisms of these activities are unclear. Because of this wide diversity of effects, it is believed that they may be exerted through pluripotent effector cells such as macrophages. The effects of acemannan on the mouse macrophage cell line, RAW 264.7 cells were therefore investigated. It was found that acemannan could stimulate macrophage cytokine production, nitric oxide release, surface molecule expression, and cell morphologic changes. The production of the cytokines IL-6 and TNF-alpha were dependent on the dose of acemannan provided. Nitric oxide production, cell morphologic changes and surface antigen expression were increased in response to stimulation by a mixture of acemannan and IFN-gamma. These results suggest that acemannan may function, at least in part, through macrophage activation.

6: Mol Pharmacol. 1996 Oct;50(4):878-84.

Acemannan, a beta-(1,4)-acetylated mannan, induces nitric oxide production in macrophage cell line RAW 264.7.

Ramamoorthy L, Kemp MC, Tizard IR. Department of Veterinary Pathobiology, Texas A & M University , College Station 77843 , USA

Acemannan is a polydispersed beta-(1,4)-linked acetylated mannan with antiviral properties. It is an immunomodulator, and studies in our laboratory have shown that it causes activation of macrophages. Inducible NO synthase is generally expressed after transcriptional induction and is known to mediate some of the cytotoxic action of activated macrophages. Acemannan, in the presence of interferon-gamma, greatly increased the synthesis of NO in RAW 264.7 cells. This increase was preceded by increased expression of mRNA for the inducible form of macrophage NO synthase. Preincubation with pyrrolidine dithiocarbamate inhibited the induction, indicating the involvement of nuclear factor-kappa B. These results suggest that acemannan causes the activation of macrophages by increasing the level of NO synthase at the level of transcription.

7: J Am Anim Hosp Assoc. 1995 Sep-Oct;31(5):439-47.

The effect of Acemannan Immunostimulant in combination with surgery and radiation therapy on spontaneous canine and feline fibrosarcomas.

King GK, Yates KM, Greenlee PG. Gulf Coast Veterinary Specialists, Inc. (King), Houston, Texas 77096, USA.

Eight dogs and five cats with histopathologically confirmed fibrosarcomas were treated with Acemannan Immunostimulanta in combination with surgery and radiation therapy. These animals had recurring disease that had failed previous treatment, a poor prognosis for survival, or both. Following four to seven weekly acemannan treatments, tumor shrinkage occurred in four (greater than 50%; n = 2) of 12 animals, with tumors accessible to measurement. A notable increase in necrosis and inflammation was observed. Complete surgical excision was performed on all animals between the fourth and seventh week following initiation of acemannan therapy. Radiation therapy was instituted immediately after surgery. Acemannan treatments were continued monthly for one year. Seven of the 13 animals remain alive and tumor-free (range, 440+ to 603+ days) with a median survival time of 372 days. The data suggests that Acemannan Immunostimulant may be an effective adjunct to surgery and radiation therapy in the treatment of canine and feline fibrosarcomas.

Publication Types:

• Clinical Trial

8: Int J Immunopharmacol. 1995 Mar;17(3):183-8.

Nitric oxide production by chicken macrophages activated by Acemannan, a complex carbohydrate extracted from Aloe vera.

Karaca K, Sharma JM, Nordgren R.
University of Minnesota, College of Veterinary Medicine, Department of Pathobiology, St Paul 55108, USA.

Cultures of normal chicken spleen cells and HD11 line cells produce nitric oxide (NO) in response to Acemannan, a complex carbohydrate derived from the Aloe vera plant. Neither cell type produced detectable amounts of NO in response to similar concentrations of yeast mannan, another complex carbohydrate. Nitric oxide production was dose dependent and inhibitable by the nitric oxide synthase inhibitor NG-methyl-L-arginine. In addition, the production of NO was inhibited by preincubation of ACM with concanavalin A in a dose-dependent manner. These results suggest that ACM-induced NO synthesis may be mediated through macrophage mannose receptors, and macrophage activation may be accountable for some of the immunomodulatory effects of ACM in chickens.

Veterinary Immunology and Immunopathology

9: Vet Immunol Immunopathol. 1992 Dec;35(1-2):177-89.

Pilot study of the effect of acemannan in cats infected with feline immunodeficiency virus.

Yates KM, Rosenberg LJ. Carrington Laboratories, Irving , TX USA

Acemannan, a complex carbohydrate shown to stimulate interleukin-1, tumor necrosis factor alpha and prostaglandin E2 production by macrophages, has also demonstrated antiviral activity in vitro against human immunodeficiency virus, Newcastle disease virus and influenza virus. A pilot study was undertaken to determine acemannan's effect in 49 feline immunodeficiency virus (FIV) infected cats with clinical signs of disease (Stage 3, 4 or 5), 23 of which had severe lymphopenia. Cats received acemannan either by intravenous (Group 1) or subcutaneous (Group 2) injection once weekly for 12 weeks, or by daily oral (Group 3) administration for 12 weeks. Upon entry into the study, cats were randomly assigned to one of the three groups. Laboratory analyses were performed at the beginning of the study and at Weeks 6 and 12. Cats were allowed to continue with a predetermined maintenance regimen of acemannan after completing the 12-week study. Thirteen cats died during the course of treatment. Upon necropsy, the most frequent histopathologic findings were neoplastic, kidney and pancreatic disease. Friedman's two-way ANOVA test showed no significant differences in efficacy among groups administered acemannan by the different routes. Therefore, groups were combined and a signed-ranks test was used to determine changes over time. A significant increase was seen in lymphocyte counts (P < 0.001). Neutrophil counts decreased significantly (P = 0.007), as did incidence of sepsis (P = 0.008). When cats entering with lymphopenia were analyzed separately, a much greater increase in lymphocyte counts was noted (235%) compared with non-lymphopenic cats (42%). A survival rate of 75% was found for all three groups. Thirty-six of 49 animals are alive 5-19 months post-entry. These results suggest that acemannan therapy may be of significant benefit in FIV-infected cats exhibiting clinical signs of disease.

10: Vet Hum Toxicol. 1992 Jun;34(3):201-5.

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Fogleman RW, Chapdelaine JM, Carpenter RH. Pharmakon Research International, Waverly, PA, USA .

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.

11: Vet Hum Toxicol. 1992 Apr;34(2):144-7.

Subchronic oral administration of acemannan in the rat and dog.

Fogleman RW, Shellenberger TE, Balmer MF. Carrington Laboratories, Dallas , TX , USA .

Acemannan is the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed O-acetyl groups, with a mannose monomer/acetyl ratio of approximately 1:1. This complex polysaccharide is extracted from Aloe vera (barbadensis Miller); the technical material contains approximately 78% acemannan. Technical grade acemannan was administered po to rats for 14 d at 5% of the diet and for 6 mo at up to 2,000 mg/kg/d, and to beagle dogs for 90 d at up to 1,500 mg/kg/d without significant effect on any parameter measured in either species.

12: Immunopharmacol Immunotoxicol. 1992;14(1-2):63-77.

The impact of acemannan on the generation and function of cytotoxic T-lymphocytes.

Womble D, Helderman JH. Department of Internal Medicine, Vanderbilt University , Nashville , Tennessee , USA .

Acemannan, an antiviral agent with immune enhancement capabilities, was studied for its impact on cytotoxic T-lymphocyte (Tc) function generated in response to alloantigen. To investigate whether acemannan directly stimulated the generation of Tc from primary mixed lymphocyte cultures (MLC), the drug was added at the initiation of the MLC. There was a dose-related, statistical increase in killer T-cell generation produced by acemannan in the clinically relevant dose range. The lowest test dose of the drug (2.6 x 10(-9) M) increased chromium release nearly two-fold; the 2.6 x 10(-8) M dose gave a maximal 3.5 fold increase in cytotoxic T-cells. To study whether acemannan enhanced the capacity of Tc once generated to alloantigen to destroy targets bearing the sensitizing antigens, MLR were established in the absence of any drug. Acemannan at the two highest doses increased the functional capacity of Tc to destroy target cells to which they had been sensitized in the MLR. To control for the possibility that acemannan was directly cytotoxic to target cells, targets were incubated alone with drug and without sensitized killer T-cells. No dose of acemannan was found to be cytotoxic to these cells. In conclusion, acemannan did enhance the generation of cytotoxic T-cells when added at the initiation of the MLR. When acemannan was added at the completion of allostimulation, an increase of almost 50% killing by Tc was also observed. These effects can not be explained by direct drug related toxicity and suggest a functional correlate to the previously described immune enhancing properties of the agent. As this drug is being tested for the treatment of HIV infections, these data provide at least one immunologic mechanism by which acemannan may be clinically salutory.

13: Vaccine. 1992;10(8):551-7.

Antigen dependent adjuvant activity of a polydispersed beta-(1,4)-linked acetylated mannan (acemannan).

Chinnah AD, Baig MA, Tizard IR. Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University , College Station , USA .

The adjuvant properties of a polydispersed beta-(1,4)-linked acetylated mannan, acemannan (ACE-M), were evaluated. Day-old broiler chicks were randomly selected and allocated to four flocks (Vac 1-4). The Vac 1 flock was sham vaccinated with saline. The Vac 2 flock was vaccinated with an oil-based vaccine (Breedervac III; Newcastle disease virus (NDV), infectious bursal disease virus (IBDV) and infectious bronchitis virus). The Vac 3 flock was vaccinated with a vaccine-ACE-M mixture, and the Vac 4 flock was vaccinated with vaccine and ACE-M at separate anatomical sites. ELISA titres to NDV and IBDV were determined. The immune response to NDV at 21 days postvaccination (PV) was significantly enhanced (P less than or equal to 0.05) by the addition of ACE-M to the vaccine, compared with vaccination without ACE-M. Subsequently, the vaccine-ACE-M mixture appeared to suppress the immune response to NDV. However, at day 35 PV, 95% of the Vac 3 chicks compared with 90% of the Vac 2 and 89% of the Vac 4 chicks exhibited protective titres. The response to IBDV differed from that to NDV. At day 21 PV the immune response to IBDV was essentially the same for all flocks that received vaccine, i.e. addition of ACE-M to the vaccine did not significantly enhance the immune response; however, it did significantly (P less than or equal to 0.05) sustain the immune response at days 28 and 35. In addition to the observed effect on titres to NDV and IBDV, ACE-M also had an effect on flock immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

14: Mol Biother. 1991 Dec;3(4):207-13.

Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms.

Harris C, Pierce K, King G. Animal Diagnostic Clinic, Dallas , Texas .

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.

15: Mol Biother. 1991 Dec;3(4):214-23.

In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir.

Kahlon JB, Kemp MC, Yawei N. Department of Biochemistry, Southern Research Institute, Birmingham , Alabama , USA .

The antiviral effects of selected combinations between acemannan (ACE-M), a long-chained, polydispersed, beta-(1,4)-acetylated mannan, were tested in combination with azidothymidine (AZT) and acyclovir (ACY) in vitro. The rationale for such combinations was based on the antiviral and immunomodulatory properties exhibited by ACE-M. In addition, the observed antiviral effects of ACE-M against human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses appear to be related to modification of the glycosylation of viral glycoproteins. Therefore, the inhibitory effect of ACE-M does not overlap with that of AZT or ACY. The studies presented herein show that ACE-M combined with suboptimal noncytotoxic concentrations of AZT or ACY act synergistically to inhibit the replication of HIV-1 and herpes simplex virus type 1 (HSV-1), respectively. The median effect method was not applicable for analysis because the test compounds show mutually nonexclusive drug effects. For a meaningful evaluation and interpretation of the effects of drug combinations, the biological significance of combinations must be considered, that is, the protective effect of the combination, the noncytotoxicity of the combination, the mechanism(s) of action of the individual compounds comprising the combination, and so forth. With respect to effects on U1 cells latently infected with HIV-1, treatment with combinations of AZT and ACE-M does not potentiate virus replication.

16: Mol Biother. 1991 Sep;3(3):127-35.

Inhibition of AIDS virus replication by acemannan in vitro.

Kahlon JB, Kemp MC, Carpenter RH. Southern Research Institute, Birmingham, AL.

Acemannan (ACE-M), a beta-(1,4)-linked acetylated mannan, was evaluated for in vitro activity against human immunodeficiency virus type 1 (HIV-1). Castanospermine (CAS), deoxymannojirimycin (DMN), swainsonine (SWS), azidothymidine (AZT), and dideoxythymidine (DDC) were tested in parallel as control compounds. In vitro antiviral efficacy of ACE-M was evaluated in a variety of cell lines including human peripheral mononuclear, CEM-SS1 and MT-2(2) cells. The virus strain, number of infectious units per cell, and target cell line were important factors in determining the degree of inhibition of viral cytopathic effect in the presence of ACE-M and other control compounds tested. Maximum inhibitory effect was observed in CEM-SS cells infected with the RFII strain of HIV-1. This inhibitory effect was determined to be concentration-dependent. Assay design included primary screening to measure cell viabilities of infected target cells in the presence and absence of test compounds. When tested on HIV-1/RFII-infected CEM-SS cells, the 50% inhibitory effect of CAS (IC50 = 28), an inhibitor of alpha-glucosidase I, was determined to be similar to that observed for ACE-M (IC50 = 45). However, DMN and SWS, inhibitors of mannosidase I and II, tested in parallel to CAS and ACE-M, exhibited no IC50 values. Antiviral potential of ACE-M as an inhibitor of syncytia formation was also explored using CEM-SS cells. Suppression of syncytia formation was observed at an ACE-M concentration of 31.25 micrograms/ml, and complete inhibition was observed at 62.5 micrograms/ml. In addition, HIV-1 RNA levels were studied to establish the antiviral potential of ACE-M in vitro.

17: J Agric Food Chem. 2003 Dec 17;51(26):7788-91.

Evaluation of Antioxidant Potential of Aloe vera (Aloe barbadensis Miller) Extracts.

Hu Y, Xu J, Hu Q. College of Food Science and Technology, Nanjing Agricultural University, Nanjing, PRC, and Department of Biology, Changshu College of Science and Technology, Changshu, PR China.

The polysaccharide and flavonoid concentrations of two-, three-, and four-year-old Aloe vera were determined, and their antioxidant activities were evaluated compared to BHT and alpha-tocopherol by the DPPH radical scavenging method and the linoleic acid system at 100 microg of soluble solids per mL of ethanol. The results showed that three-year-old Aloe vera contained significantly higher levels of polysaccharides and flavonoids than two- and four-year-old Aloe vera, and no significant differences in flavonoid levels were found between three- and four-year-old Aloe vera. All the aloe extracts showed significant antioxidant activity. The antioxidant activity of Aloe vera extracts and reference compounds followed the order: three-year-old Aloe vera > BHT > four-year-old Aloe vera > alpha-tocopherol > two-year-old Aloe vera. The three-year-old extract exhibited the strongest radical scavenging activity of 72.19%, which is significantly higher than that of BHT at 70.52% and alpha-tocopherol at 65.20%. These data suggest that the growth stage plays a vital role in the composition and antioxidant activity of Aloe vera.

18: Burns. 2003 Dec;29(8):834-6.

Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin.

Muller MJ, Hollyoak MA, Moaveni Z. Plastic Surgery and Burns Unit, Middlemore Hospital, P.O. Box 93311, Otahuhu, Auckland, New Zealand.

Inhibition of wound contraction by topical anti microbial agents has been described. The purpose of this study was to further investigate that phenomenon and to explore the effect that other agents such as Aloe vera might have on this process. Full-thickness excised wounds were created on the dorsum of Sprague-Dawley rats under anaesthesia. The wounds were treated with topical agents three times daily for fourteen days, then observed until healed. Groups were: saline control, placebo (aqueous cream) control, silver sulphadiazine (SSD) cream 1%, SSD 0.5%, SSD 1% with Aloe vera, SSD 1% with nystatin, nystatin. Wound surface areas were measured each three days. Time to 50% and 90% healing was compared using ANOVA. Wound half-life and healing times were shortest in the SSD/Aloe vera and nystatin groups (P<0.05) and longest in the 1% SSD and saline control groups. The placebo group (aqueous cream) healed in a significantly shorter time (P<0.05) than the control (saline) group. Wound contraction was delayed by saline and SSD. Nystatin and Aloe vera, when added to SSD, reversed that effect.These data suggest that a dry wound (saline) heals slowly. Infection control without delay of wound healing is most appealing and clinical trials are planned.

19: J Altern Complement Med. 2003 Oct;9(5):711-8.

Effects of Aloe vera on gap junctional intercellular communication and proliferation of human diabetic and nondiabetic skin fibroblasts.

Abdullah KM, Abdullah A, Johnson ML. Department of Surgery, School of Medicine, University of North Dakota, Grand Forks, ND, USA.

OBJECTIVE: To evaluate the effects of Aloe vera on gap junctional intercellular communication (GJIC) and proliferation of human skin fibroblasts in the presence or absence of basic fibroblast growth factor (FGF-2). DESIGN: In vitro study using human type II diabetic and nondiabetic skin fibroblast cell lines. SETTING AND SUBJECTS: Diabetic (n = 4) and nondiabetic (n = 4) human skin fibroblast cell lines were purchased from Coriell Institute for Medical Research ( Camden , NJ ). The cells were cultured with or without Aloe vera extract in increasing concentrations (0%, 0.625%, 1.25%, 2.5%, 5%, 10%, and 20%; v/v) in culture medium and with or without FGF-2 (30 ng/mL). MEASUREMENTS: GJIC was evaluated after 48-hour incubation with treatments by laser cytometry. Cells were counted after 72-hour incubation with treatments by using a Coulter counter. RESULTS: The rate of GJIC was greater (p < 0.01) for diabetic than for nondiabetic fibroblasts (3.5 +/- 0.1 versus 3.0 +/- 0.1% per minute during the first 4 minutes after photobleaching). GJIC was increased ( p < 0.05) for diabetic fibroblasts in the presence of 2.5% and 5% of Aloe vera extract (4.2 +/- 0.1 and 4.0 +/- 0.2 versus 3.5 +/- 0.1% per minute for control, respectively). FGF-2 stimulated (p < 0.01) GJIC for diabetic (4.0 +/- 0.1 versus 3.5 +/- 0.1% per minute for control) and nondiabetic (3.5 +/- 0.1 versus 3.0 +/- 0.1% per minute for control) fibroblasts. Aloe vera extract did not affect GJIC of nondiabetic fibroblast cultured without FGF-2. However, Aloe vera extract decreased (p < 0.05) FGF-2 stimulatory effects on GJIC of diabetic and nondiabetic fibroblasts. Proliferation of diabetic fibroblasts was increased (p < 0.05) by 1.25% and 2.5% Aloe vera extract in medium. Proliferation of nondiabetic fibroblasts was not affected by Aloe vera extract. FGF-2 increased (p < 0.05) proliferation of nondiabetic fibroblasts and FGF-2 did not affect proliferation of diabetic fibroblasts. Aloe vera extract decreased (p < 0.05) FGF-2 stimulatory effects on proliferation of nondiabetic fibroblasts. CONCLUSIONS: These data demonstrate that Aloe vera has the ability to stimulate GJIC and proliferation of human skin fibroblasts in diabetes mellitus. Furthermore, these results indicate that Aloe vera contains a compound(s) that neutralizes, binds with FGF-2 receptor, or otherwise alters signaling pathways for FGF-2. By affecting both GJIC and proliferation of diabetic fibroblasts, Aloe vera may improve wound healing in diabetes mellitus.

20: J Nutr Sci Vitaminol ( Tokyo ). 2003 Aug;49(4):292-6.

Efficacy of dietary aloe vera supplementation on hepatic cholesterol and oxidative status in aged rats.

Lim BO, Seong NS , Choue RW. , Kim JD, Lee HY, Kim SY, Yu BP, Jeon TI, Park DK.
Graduate School of East-West Medical Science, Kyung Hee University, Korea.

In the current study, we show the anti-oxidative and hypocholesterol effects of aloe vera in the liver. Male specific pathogen-free (SPF) Fischer 344 rats were randomly assigned to one of four groups: Group A (control) was fed test chow without aloe supplementation; Group B was fed a diet containing a 1% (per weight basis) freeze-dried aloe filet; Group C was fed a diet containing a 1% (per weight basis) charcoal-processed, freeze-dried aloe filet; and Group D was fed a diet containing a charcoal-processed freeze-dried, whole leaf aloe (0.02% per weight basis) in the drinking water. Our results show that a life-long intake of aloe had superior anti-oxidative action against lipid peroxidation in vivo, as indicated by reduced levels of hepatic phosphatidylcholine hydroperoxide. Additional anti-oxidative action was evidenced by enhanced superoxide dismutase (SOD) and catalase activity in groups B and C. Furthermore, our study revealed that hepatic cholesterol significantly increased in the control group during aging in contrast to the aloe-supplemented groups, which showed approximately 30% lower cholesterol levels, thereby an effective hypocholesteremic efficacy. In this report, we suggest that life-long dietary aloe supplementation suppresses free radical-induced oxidative damage and age-related increases in hepatic cholesterol.

21: Angiogenesis. 1999;3(2):117-23.

A novel angiogenic factor derived from Aloe vera gel: beta-sitosterol, a plant sterol.

Moon EJ, Lee YM, Lee OH. Department of Molecular Biology, Pusan National University , Pusan , Korea .

Aloe vera gel has a beneficial effect on wound healing. Because angiogenesis is an essential process in wound healing, we hypothesized that Aloe vera gel might contain potent angiogenic compounds. Here we demonstrate that Aloe vera gel and its extracts are angiogenic on the chorioallantoic membrane ( CAM ) of chick embryo. Out of the three compounds purified from the final fraction of Aloe vera gel, beta-sitosterol showed a potent angiogenic activity in the CAM assay. In the presence of heparin, beta-sitosterol stimulated neovascularization in the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay. Thus beta-sitosterol is a novel plant-derived angiogenic factor which may have potential pharmaceutical applications for the management of chronic wounds

22: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao ( Shanghai ). 2003 May;35(5):423-9.

Induced expression of the gene for NADP-malic enzyme in leaves of Aloe vera L. under salt stress.

Sun SB, Shen QR, Wan JM. College of Resources and Environmental Science, Nanjing , China .

A cDNA fragment for NADP-malic enzyme, catalyzing the reversible oxidative decarboxylation of L-malate to produce CO(2), pyruvate and NADPH, was isolated from the leaves of a 2-month-old Aloe vera L., The level of expression of NADP-ME mRNA and accumulation of NADP-ME (AvME) protein under salt stress conditions were compared between a tolerant aloe, Aloe vera L. and a sensitive aloe, Aloe saponarea Haw. The results suggested that both the expression of the gene and the accumulation of the protein were induced in the two kinds of aloe, and the strength was related to the degree of salt tolerance. Northern blot analysis revealed that the gene for NADP-malic enzyme in Aloe vera L.( AvME) was induced by high salt, dehydration, and exogenous abscisic acid ( ABA ), but not by cold treatment. To further confirm whether the synthesis of AvME protein was induced with hours of treatment, Western blot analysis of the samples was conducted. The results indicated that the induction of AvME protein expression was obvious after 48 h at high salt and the level was increased with the hours of treatment.

23: Russ J Immunol. 1999 Apr;4(1):43-50.

Modulation of Immune Response of BALB/Mice Bearing Lymphoma L5178Y Treated with Bitter Yellow Juice of Aloe vera (L) in vivo.

Oronzo-Barocio A, Zaitseva G. University of Guadalajara, Mexico.

Aloe vera (L), a plant of African origin, has been introduced in Mexico since XVIth century. It has been used in the treatment of many diseases of immune system. In the present study we investigated a specific and non-specific immune response of BALB/c mice, healthy and immunosuppressed with murine lymphoma L5178Y, treated with bitter yellow juice (extract) of Aloe vera (L). We observed that the immunosuppressed mice, treated with the whole extract of the bitter yellow juice achieved restoration of immunological parameters in cellular immune response and phagocytosis. On the other hand, the humoral immunity was not restored. Also, in the healthy rodents treated with the extract, it caused the stimulation of specific and non-specific responses, the results had significant differences with the obtained ones in untreated mice.

24: Planta Med. 2003 Mar;69(3):269-71.

Radical scavenging glycoprotein inhibiting cyclooxygenase-2 and thromboxane A2 synthase from aloe vera gel.

Yagi A, Kabash A, Mizuno K. Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuen-Cho, Hiroshima, Japan.

An active glycoprotein fraction containing 58 % protein was isolated from Aloe vera gel by precipitation with 55 % ammonium sulfate followed by gel permeation using DEAE-Sephacel A-25, Sepharose 6B and Sephadex G-50 columns in a yield of 3 x 10 -3 %. The glycoprotein fraction showed a single band corresponding to a subunit of verectin at the same position when stained with both Coomassie brilliant blue and periodic acid-Schiff reagents on 18 % SDS-PAGE. The molecular weight (14 kDa) was confirmed by Sephadex G-50 column chromatography. The glycoprotein fraction showed a radical scavenging activity against superoxide anion generated by the xanthine-xanthine oxidase system as well as inhibition of cyclooxygenase-2 and reduction of thromboxane A 2 synthase level in vitro.

25: Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2002 May;16(5):229-31.

[Molecular biological study of aloe vera in the treatment of experimental allergic rhinitis in rat]

Yu H, Dong Z, Yang Z. Department of Otolaryngology-Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, PR China.

OBJECTIVE: To study the therapeutic mechanism of aloe vera in allergic rhinitis (AR). METHOD: Ovalbumin sensitized white rat used as animal models of AR were treated intranasally with aloe vera. At the end of treatment, the differences in the behavior science were observed; the changes in the nasal mucosa were studied by pathological; IL-2, IL-4 mRNA in the nasal mucosa and spleen were used to do reverse transcriptive polymerase chain reaction (RT-PCR). RESULT: The behavior science score of positive controls (8.42 +/- 1.06) was higher than the experimental group (2.02 +/- 0.42) and normal controls (0); inflammatory reactions in the experimental group nasal mucosa were remarkably relieved; the mean expression level of IL-2 mRNA in the experimental group was higher significantly than positive controls (P < 0.01); but that of IL-4 mRNA was lower evidently (P < 0.01). CONCLUSION: The aloe vera are suggested to be involved in the differentiation of CD4+ lymphocytes, by means of regulating the expression of Th1 and Th2 cytokines. The results suggests that local aloe vera treatment was a selective and non-traumatic method to treat the allergic rhinitis.

26: Am J Infect Control. 2003 Feb;31(1):40-2.

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure.

West DP, Zhu YF. Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, Ill 60611-2923, USA.

OBJECTIVE: An examination glove that delivers aloe vera (AV) gel to the gloved hand was studied in 30 adult females with bilateral occupational dry skin with or without irritant contact dermatitis (with or without erythema, fissures, and excoriations). METHODS: All participants were factory assembly-line workers with repeated superficial skin trauma who attributed their dry, irritated, emollient-dependent skin to a common cause (occupational exposure). Participants were sequentially enrolled (after written informed consent, n = 29 evaluable participants) into an open, contralateral comparison study to evaluate efficacy of AV glove use 8 h/day to one hand versus no use to the opposite hand for 30 days, followed by 30 days rest, followed by 10 days of repeated use. Participant's dorsal hands were documented by standardized photos at baseline, during, and at the end of study. RESULTS: Unblinded investigator baseline assessment rated dry skin as mild to moderate (n = 27), or moderate to severe (n = 2). Mean time to noticeable improvement for the AV glove hand was 3.5 days (range: 2-6 days) whereas marked improvement was 10.4 days (range: 7-17 days) for the AV glove hand. No improvement was detected for nonglove hands.Blinded photo assessment was rated independently by dermatology research staff. End-of-study mean global assessment of AV glove hands versus nonglove hands was 1.3 for AV glove hand (0 = no change, 1 = good [10%-89% global improvement], 2 = marked improvement [90%-100% global improvement]) versus 0 for nonglove hand (P <.0001). Mean global end-of-study assessments by the participants = 2.0 for AV glove hand versus 0 for nonglove hand. CONCLUSION: Dry-coated AV gloves that provide for gradual delivery of AV gel to skin produced a uniformly positive outcome of improved skin integrity, decreased appearance of fine wrinkling, and decreased erythema in the management of occupational dry skin and irritant contact dermatitis.

Publication Types:

• Clinical Trial

• Controlled Clinical Trial

27: Cancer Nurs. 2002 Dec;25(6):442-51.

A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.

Heggie S, Bryant GP, Tripcony L. Queensland Radium Institute, Division of Oncology, Royal Brisbane Hospital , Australia .

The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, ie, breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects. A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields. Patients were randomized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment. Weekly skin assessments were performed by nursing staff. Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment. Subjects with D cup or larger size breasts experienced significantly more erythema, regardless of treatment arm. For subjects who had undergone lymphocele drainage, the aloe vera group experienced significantly more pain than the aqueous cream group. Within the aqueous cream arm, smokers were significantly more likely to experience itching within the treatment field than were nonsmokers. Within the aloe vera arm, subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage. In this study, aloe vera gel did not significantly reduce radiation-induced skin side effects. Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy.

Publication Types:

• Clinical Trial

• Clinical Trial, Phase III

• Randomized Controlled Trial

28: Phytother Res. 2002 Dec;16(8):712-8.

The influence of long-term Aloe vera ingestion on age-related disease in male Fischer 344 rats.

Ikeno Y, Hubbard GB, Lee S. Department of Physiology, University of Texas Health Science Center, San Antonio, Texas, USA.

The effects of long-term Aloe vera ingestion on age-related diseases were investigated using male specific pathogen-free (SPF) Fischer 344 rats. Experimental animals were divided into four groups: Group A, the control rats fed a semi-synthetic diet without Aloe vera; Group B, rats fed a diet containing 1% freeze-dried Aloe vera filet; Group C, rats fed a diet containing 1% charcoal-processed, freeze-dried Aloe vera filet; and Group D, rats fed the control diet and given whole leaf charcoal-processed Aloe vera (0.02%) in the drinking water. This study demonstrates that life-long Aloe vera ingestion produced neither harmful effects nor deleterious changes. In addition, Aloe vera ingestion appeared to be associated with some beneficial effects on age-related diseases. Groups B exhibited significantly less occurrence of multiple causes of death, and a slightly lower incidence of fatal chronic nephropathy compared with Group A rats. Groups B and C rats showed the trend, slightly lower incidences of thrombosis in the cardiac atrium than Group A rats. Therefore, these findings suggest that life-long Aloe vera ingestion does not cause any obvious harmful and deleterious side effects, and could also be beneficial for the prevention of age-related pathology.

29: Planta Med. 2002 Nov;68(11):957-60.

Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera.

Yagi A, Kabash A, Okamura N. Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuen-cho, Japan.

Antioxidant components in Aloe vera were examined for lipid peroxidation using rat liver microsomal and mitochondrial enzymes. Among the aloesin derivatives examined, isorabaichromone showed a potent antioxidative activity. The DPPH radical and superoxide anion scavenging activities were determined. As one of the most potent components, isorabaichromone together with feruloylaloesin and p-coumaroylaloesin showed potent DPPH radical and superoxide anion scavenging activities. Electron spin resonance (ESR) using the spin trapping method suggested that the potent superoxide anion scavenging activity of isorabaichromone may have been due to its caffeoyl group. As A. vera has long been used to promote wound healing, the inhibitory effects of aloesin derivatives for cyclooxygenase (Cox)-2 and thromboxane (Tx) A 2 synthase were examined and the participation of p-coumaroyl and feruloyl ester groups in the aloesin skeleton was demonstrated. These findings may explain, at least in part, the wound healing effects of A.vera. Abbreviations. ADP:adenosine diphosphate ASA:ascorbic acid BHT:butylated hydroxytoluene BSA:bovine serum albumin DMPO:5,5-dimethyl-1-pyrroline N-oxide DPPH:1,1-diphenyl-2-picrylhydrazyl EDTA:edetic acid HEPES: N-(2-hydroxyethyl)-piperazine- N-2'-ethane-sulfonic acid NADH:reduced nicotinamide adenine dinucleotide NADPH:reduced nicotinamide adenine dinucleotide phosphate NBT:nitroblue tetrazolium Pg:prostaglandin SOD:superoxide dismutase TBA:thiobarbituric acid TCA:trichloroacetic acid XOD:xanthine oxidase

30: Br J Dermatol. 2001 Oct;145(4):535-45.

The wound-healing effect of a glycoprotein fraction isolated from aloe vera.

Choi SW, Son BW, Son YS. Department of Pharmacology, Seoul National University College of Medicine, Seoul , Korea .

BACKGROUND: Aloe vera has been used as a family medicine for promoting wound healing, but it is not known which component of the plant is effective for this purpose. OBJECTIVES: To isolate and characterize the component effective in wound healing. METHODS: Chromatography, electrophoresis and spectroscopic methods were used. The cell-proliferation activity of each component isolated was measured by a [3H]thymidine uptake assay. The cell-proliferation activity of the effective component was tested on a three-dimensional raft culture (cell culture technique by which artificial epidermis is made from keratinocytes). The effect of the active component on cell migration and wound healing was observed on a monolayer of human keratinocytes and in hairless mice. RESULTS: A glycoprotein fraction was isolated and named G1G1M1DI2. It showed a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, with an apparent molecular weight of about 5.5 kDa. It exhibited significant [3H]thymidine uptake in squamous cell carcinoma cells. The effect of G1G1M1DI2 on cell migration was confirmed by accelerated wound healing on a monolayer of human keratinocytes. When this fraction was tested on a raft culture, it stimulated the formation of epidermal tissue. Furthermore, proliferation markers (epidermal growth factor receptor, fibronectin receptor, fibronectin, keratin 5/14 and keratin 1/10) were markedly expressed at the immunohistochemical level. The glycoprotein fraction enhanced wound healing in hairless mice by day 8 after injury, with significant cell proliferation. CONCLUSIONS: It is considered that this glycoprotein fraction is involved in the wound-healing effect of aloe vera via cell proliferation and migration.

31: Phytother Res. 2001 Mar;15(2):157-61.

Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models.

Okyar A, Can A, Akev N. Pharmacology, Faculty of Pharmacy, University of Istanbul , 34452 Universite, Istanbul , Turkey .

Aloe vera (L.) Burm. fil. (= A. barbadensis Miller) (Liliaceae) is native to North Africa and also cultivated in Turkey . Aloes have long been used all over the world for their various medicinal properties. In the past 15 years, there have been controversial reports on the hypoglycaemic activity of Aloe species, probably due to differences in the parts of the plant used or to the model of diabetes chosen. In this study, separate experiments on three main groups of rats, namely, non-diabetic (ND), type I (IDDM) and type II (NIDDM) diabetic rats were carried out. A. vera leaf pulp and gel extracts were ineffective on lowering the blood sugar level of ND rats. A. vera leaf pulp extract showed hypoglycaemic activity on IDDM and NIDDM rats, the effectiveness being enhanced for type II diabetes in comparison with glibenclamide. On the contrary, A. vera leaf gel extract showed hyperglycaemic activity on NIDDM rats. It may therefore be concluded that the pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of non-insulin dependent diabetes mellitus.

32: J Agric Food Chem. 2001 Feb;49(2):1030-4.

Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity.

Pugh N, Ross SA, ElSohly MA. Department of Pharmacognosy, National Center for Natural Products Research, University of Mississippi , USA .

We have characterized a new immunostimulatory polysaccharide called Aloeride from commercial aloe vera (Aloe barbadensis) juice. Aloeride is between 4 and 7 million Da, and its glycosyl components include glucose (37.2%), galactose (23.9%), mannose (19.5%), and arabinose (10.3%). At 0.5 microg/mL Aloeride increased NF-kappa B directed luciferase expression in THP-1 human monocytic cells to levels 50% of those achieved by maximal concentrations (10 microg/mL) of LPS. Aloeride induced the expression of the mRNAs encoding IL-1beta and TNF-alpha to levels equal to those observed in cells maximally activated by LPS. Acemannan, the major carbohydrate component from aloe, used at 200 microg/mL in the macrophage assay resulted in negligible NF-kappa B activation. Analysis of acemannan and Aloeride using size-exclusion chromatography suggests that the low activity of acemannan is due to trace amounts of Aloeride. Although Aloeride comprises only 0.015% of the aloe juice dry weight, its potency for macrophage activation accounts fully for the activity of the crude juice.

33: Phytomedicine. 2000 Jun;7(3):209-19.

Chemomodulatory action of Aloe vera on the profiles of enzymes associated with carcinogen metabolism and antioxidant status regulation in mice.

Singh RP, Dhanalakshmi S, Rao AR. Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

The effect of two doses (30 microl and 60 microl/day/mice daily for 14 days) of the fresh leaf pulp extract of Aloe vera was examined on carcinogen-metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of mice. The modulatory effect of the pulp extract was also examined on extrahepatic organs (lung, kidney and forestomach) for the activities of glutathione S-transferase, DT-diophorase, superoxide dismutase and catalase. The positive control mice were treated with butylated hydroxyanisole (BHA). Significant increases in the levels of acid soluble sulfhydryl (-SH) content, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase (GR) were observed in the liver. Aloe vera significantly reduced the levels of cytochrome P450 and cytochrome b5. Thus, Aloe vera is clearly an inducer of phase-II enzyme system. Treatment with both doses of Aloe caused a decrease in malondialdehyde (MDA) formation and the activity of lactate dehydrogenase in the liver, suggesting its role in protection against prooxidant-induced membrane and cellular damage. The microsomal and cytosolic protein was significantly enhanced by Aloe vera, indicating the possibility of its involvement in the induction of protein synthesis. BHA, an antioxidant compound, provided the authenticity of our assay protocol and response of animals against modulator. The pulp extract was effective in inducing GST, DTD, SOD and catalase as measured in extrahepatic organs. Thus, besides liver, other organs (lung, kidney and forestomach) were also influenced favorably by Aloe vera in order to detoxify reactive metabolites, including chemical carcinogens and drugs.

34: J Pharm Pharmacol. 2000 Aug;52(8):1037-41.

Induction of apoptosis in human leukaemic cell lines K562, HL60 and U937 by diethylhexylphthalate isolated from Aloe vera Linne.

Lee KH, Hong HS, Lee CH. Animal Resource Research Center , Konkuk University , Seoul , Korea .

We investigated the effect of diethylhexylphthalate (DEHP) from Aloe vera Linne on the apoptosis of human leukaemic cell lines K562, HL60 and U937 to examine its pharmacological activity. At a level of 10 microg mL(-1) DEHP a significant anti-leukaemic effect was observed for all three cell lines, as measured by clonogenic assay. After treatment with 10 microg mL(-1) DEHP for 4 h, agarose gel electrophoresis and flow cytometric analysis confirmed the occurrence of apoptosis. These results indicate that DEHP isolated from Aloe vera Linne has a potent antileukaemic effect, and thus represents a new type of pharmacological activity with respect to human leukaemic cells.

35: J Pharm Pharmacol. 2000 May;52(5):593-8.

Anti-leukaemic and anti-mutagenic effects of di(2-ethylhexyl)phthalate isolated from Aloe vera Linne.

Lee KH, Kim JH. Animal Resource Research Center , Konkuk University , Seoul , Korea .

Extracts of Aloe vera Linne have been found to exhibit cytotoxicity against human tumour cell lines. This study examines the anti-tumour effects of di(2-ethylhexyl)phthalate (DEHP) isolated from Aloe vera Linne, in human and animal cell lines. Its anti-mutagenic effects were examined using Salmonella typhimurium TA98 and TA100 strains. Growth inhibition was specifically exerted by DEHP against three leukaemic cell lines at concentrations below 100 microg mL(-1). At 100 microg mL(-1) DEHP, K562, HL60 and U937 leukaemic cell lines showed growth inhibition of 95, 97 and 95%, respectively. DEHP exhibited an inhibitory activity of 74, 83 and 81%, respectively, in K562, HL60 and U937 cell lines at a concentration of 10 microg mL(-1). At a concentration of 1 microg mL(-1), DEHP exerted an inhibitory activity of 50, 51 and 52%, respectively, in K562, HL60 and U937. In a normal cell line, MDBK, DEHP exerted 30% growth inhibition at a concentration of 100 microg mL(-1), and showed no inhibitory activity at concentrations below 50 microg mL(-1). It was found that DEHP exerted anti-mutagenic activity in the Salmonella mutation assay. The number of mutant colonies of Salmonella typhimurium strain TA98 upon exposure to AF-2 (0.2 microg/plate) decreased in a concentration-dependent manner in the presence of different DEHP concentrations (decreasing to 90.4, 83.9, 75.4, 69.6 and 46.9%, respectively, for DEHP concentrations of 100, 50, 10, 5 and 1 microg/plate). In the case of Salmonella typhimurium strain TA100, DEHP reduced AF-2-induced mutagenicity at 1, 5, 10, 50 and 100 microg/plate to 57.4, 77.5, 80.0, 89.0 and 91.5%, respectively. The isolated compound from Aloe vera Linne, DEHP, was considered to be the active principle responsible for anti-leukaemic and anti-mutagenic effects in-vitro.

36: J Med Assoc Thai. 2000 Apr;83(4):417-25.

Therapeutic effects of Aloe vera on cutaneous microcirculation and wound healing in second degree burn model in rats.

Somboonwong J, Thanamittramanee S, Jariyapongskul A. Department of Physiology, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand.

OBJECTIVE: To demonstrate the microcirculatory and wound healing effects of Aloe vera on induced second degree burn wounds in rats. METHOD: A total of 48 male Wistar rats were equally divided into 4 groups as follows: sham controls, untreated burn-wound rats, those treated with once-daily application of normal saline (NSS) and those treated with once-daily application of lyophilized Aloe vera gel. The animals in each group were equally subdivided into 2 subgroups for the study of cutaneous microcirculation and wound healing on day 7 and 14 after burn. Dorsal skinfold chamber preparation and intravital fluorescence microscopic technique were performed to examine dermal microvascular changes, including arteriolar diameter, postcapillary venular permeability and leukocyte adhesion on postcapillary venules. RESULTS: On day 7, the vasodilation and increased postcapillary venular permeability as encountered in the untreated burn were found to be reduced significantly (p < 0.05) in both the NSS- and Aloe vera-treated groups, but to a greater extent in the latter. Leukocyte adhesion was not different among the untreated, NSS- and Aloe vera-treated groups. On day 14, vasoconstriction occurred after the wound had been left untreated. Only in the Aloe vera-treated groups, was arteriolar diameter increased up to normal condition and postcapillary venular permeability was not different from the sham controls. The amount of leukocyte adhesion was also less observed compared to the untreated and NSS- treated groups. Besides, the healing area of the Aloe vera-treated wound was better than that of the untreated and NSS- treated groups during 7 and 14 days after burn. CONCLUSION: Aloe vera could exhibit the actions of both anti-inflammation and wound healing promotion when applied on a second degree burn wound.

37: Gen Dent. 1999 May-Jun;47(3):268-72.

Lichen planus--report of successful treatment with aloe vera.

Hayes SM.

Lichen planus is a disease that involves the skin and mucous membranes. It is characterized by unique eruptions. The cause of this disease is unknown, but has been linked to emotional stress, and has also been attributed to viral infections. A case is described of a successful treatment of lichen planus.

Publication Types:

• Case Reports

38: J Ethnopharmacol. 1999 Dec 15;68(1-3):3-37.

Aloe vera leaf gel: a review update.

Reynolds T, Dweck AC. Jodrell Laboratory, Royal Botanic Gardens, Kew, Richmond , Surrey , UK .

Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas. Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components. A common theme running though much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents. There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens. There are also cautionary investigations warning of possible allergic effects on some patients. Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel. Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities

Publication Types:

• Review

• Review Literature

39: Phytother Res. 1999 Nov;13(7):580-3.

Initial characterization of the effects of Aloe vera at a crayfish neuromuscular junction.

Friedman RN, Si K. Section of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.

This study examines the effects of Aloe vera on neurotransmission processes in a well-established invertebrate neuromuscular junction preparation. We studied concentration-response relationships of an Aloe vera extract on excitatory junctional potentials (EJPs) at the opener muscle of the dactyl in the first and second walking limbs of crayfish (Procambarus clarkii and simulans). We observed concentration-dependent depolarizations of the muscle fibre membrane resting potential, depression of EJP amplitudes and an increase in latency to onset of the EJP following electrical stimulation of the isolated excitatory axon in the meropodite. These effects occurred with Aloe concentrations within the 1%-10% (wt-vol) range. Effects of lower concentrations, ranging to a minimum of 0.01% were equivocal. The effects of Aloe were at least partially, and in a majority of cases totally, reversible. EJPs reduced by Aloe could be restored by increasing the nerve stimulation amplitude. This, along with the latency increase, suggests a depression of action potential generation and conduction. The results provide a preliminary characterization of the effects of Aloe vera on the neurotransmission process and suggest that these effects may at least partially account for Aloe's analgesic and antiinflammatory effects. This study shows that the crayfish NMJ preparation should be useful for further elucidating the location(s) and mechanism(s) of action of Aloe on the nervous system.

40: Int J Immunopharmacol. 1999 May;21(5):303-10.

Prevention of ultraviolet radiation-induced suppression of contact hypersensitivity by Aloe vera gel components.

Lee CK, Han SS, Shin YK . College of Pharmacy , Chungbuk National University , Cheongju , South Korea .

We have recently reported that Aloe vera gel contains small molecular weight immunomodulators, G1C2F1, that restore ultraviolet B (UVB)-suppressed accessory cell function of epidermal Langerhans cells (LC) in vitro. In the present study we evaluated the UVB-protective activity of G1C2F1 in vivo. Exposure of the shaved abdominal skin of mice to 2.4 KJ/m2 of UVB radiation resulted in suppression of contact sensitization through the skin to 41.1%, compared to normal unirradiated skin. Topical application of G1C2F1 immediately after irradiation reduced this suppression significantly. The percentage recovery of UVB-suppressed contact hypersensitivity (CHS) response was 52.3, 77.3, and 86.6% when the irradiated skin was treated once with 0.1, 0.5, and 2.5 mg/ml of G1C2F1-containing cream, respectively. G1C2F1 did not show nonspecific stimulatory activity on CHS response. The present study, together with the previous observation, show that Aloe vera gel contains small molecular weight immunomodulators that prevent UVB-induced immune suppression in the skin by restoration of UVB-induced damages on epidermal LC.

41: Int J Tissue React. 1998;20(4):115-8.

The therapeutic potential of Aloe Vera in tumor-bearing rats.

Corsi MM, Bertelli AA, Gaja G. , Fulgenzi A, Ferrero ME.
Institute of General Pathology, Medical Faculty, University of Milan, Italy.

Aloe Vera has been claimed to contain several important therapeutic properties, including anticancer effects. The effect of Aloe Vera administration was studied on a pleural tumor in rat. Growth of Yoshida AH-130 ascite hepatoma cells injected (2 x 10(5) in 0.1 ml) into pleura of male inbred Fisher rats was evaluated at different times (7th and 14th days). Data show that the use of Aloe Vera proved a therapeutic method, and that the present experimental model could be useful in the study of other therapeutics treatments in vivo.

42: Arch Pharm Res. 1998 Jun;21(3):260-5.

In vitro angiogenic activity of Aloe vera gel on calf pulmonary artery endothelial (CPAE) cells.

Lee MJ, Lee OH, Yoon SH. Institute of Biotechnology , Yeungnam University , Taegu , Korea .

Angiogenic activity of Aloe vera gel was investigated by in vitro assay. We obtained the most active fraction from dichloromethane extract of Aloe vera gel by partitioning between hexane and 90% aqueous methanol. The most active fraction (F3) increased the proliferation of calf pulmonary artery endothelial (CPAE) cells. In addition, F3 fraction induced CPAE cells to invade type 1 collagen gel and form capillary-like tube through in vitro angiogenesis assay, and increased the invasion of CPAE cells into matrigel through in vitro invasion assay. Furthermore, the effect on the mRNA expression of proteolytic enzymes which are key participants in the regulation of extracellular matrix degradation was investigated by northern blot analysis. F3 fraction enhanced mRNA expression of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase-2 (MMP-2), and membrane-type MMP (MT-MMP) in CPAE cells whereas the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA was not changed.

43: Indian J Exp Biol. 1998 Sep;36(9):896-901.

Influence of Aloe vera on collagen turnover in healing of dermal wounds in rats.

Chithra P, Sajithlal GB, Chandrakasan G. Department of Biochemistry, Central Leather Research Institute, Adyar, Chennai , India .

Treatment of full-thickness wounds with A. vera, on rats resulted in increased biosynthesis of collagen and its degradation. A corresponding increase in the urinary excretion of hydroxyproline was also observed. Elevated levels of lysyl oxidase also indicated increased crosslinking of newly synthesised collagen. The results suggest that A. vera influences the wound healing process by enhancing collagen turnover in the wound tissue.

44: Nutrition. 1998 Nov-Dec;14(11-12):846-52.

Vitamin C and aloe vera supplementation protects from chemical hepatocarcinogenesis in the rat.

Shamaan NA, Kadir KA, Rahmat A. Department of Biochemistry and Microbiology, Universiti Putra Malaysia , Selangor , Malaysia .

The effects of vitamin C and aloe vera gel extract supplementation on induced hepatocarcinogenesis in male Sprague-Dawley rats (120- 150 g ) by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) was investigated. The severity of the carcinogenesis process was determined by measuring gamma-glutamyl transpeptidase (GGT) and the placental form of glutathione S-transferase (GSTP) histochemically in situ and in plasma and liver fractions. In addition, plasma alkaline phosphatase (ALP) and liver microsomal uridine diphosphate glucuronyl transferase (UDPGT) activity were also determined. Administration of DEN/AAF caused an increase in the surface area and number of enzyme-positive foci (both GGT and GSTP) compared with control. Supplementation of vitamin C or aloe vera gel extract to the cancer-induced rats suppressed this increase significantly (P < 0.05; P < 0.001). Increases in liver UDPGT, GGT, and GSTP activities were also observed with cancer induction that were again suppressed with either vitamin C or aloe vera gel supplementation. Plasma GGT in the DEN/AAF rats were determined monthly for the duration of the experiment and found to be reduced as early as 1 mo with aloe vera gel supplementation and 2 mo with vitamin C supplementation. In conclusion, vitamin C and aloe vera gel extract supplementation were found to be able to reduce the severity of chemical hepatocarcinogenesis.

45: Nat Immun. 1998;16(1):27-33.

Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms.

Lissoni P, Giani L, Zerbini S, Trabattoni P, Rovelli F.
Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.

The possibility of natural cancer therapy has been recently suggested by advances in the knowledge of tumor immunobiology. Either cytokines such as IL-2, or neurohormones, such as the pineal indole melatonin (MLT), may activate anticancer immunity. In addition, immunomodula