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Es una planta conocida
desde el siglo 19, nativa de las regiones
madereras del centro y sur de los EE.UU.
que ha sido utilizada tradicionalmente en
el tratamiento antiespasmódico de
la dismenorrea (1)
y otros dolores causados por contracción
de la musculatura lisa. También en
la amenaza de parto prematura (2),
y para aumentar el tono uterino luego de
remoción quirúrgica de fibromas
(3).
Pertenece a la familia Caprifoliaceae, en
la cual existen más de 15 distintos
géneros. La prescripción de
V. prunifolium a menudo se intercambia con
la de V. opulus, ya que su efecto terapéutico
es similar, sin embargo, los principios
activos antiespasmódicos de V. prunifolium
son las cumarinas mientras que el antiespasmódico
de V. opulus es el viopudial (8).
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PRESIONE
LA BOTELLA PARA CONOCER LA PLANTA |
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Descripción
Un arbusto deciduo con tronco
erecto. Hojas verdes suaves finamente aserradas,
opuestas, elípticas a ovales. Flores blancas
pequeñas en racimos sésiles de 10
cm de ancho. Los frutos son bayas negro-azuladas
comestibles.
Parte Utilizada
La corteza del tronco, las ramas y la raíz.
Usos tradicionales
La acerola negra ha sido utilizada
tradicionalmente en el tratamiento de la disentería
y para detener hemorragias uterinas. [4,5]. Hoy
día se considera un tratamiento específico
para el alivio del dolor menstrual, debido a su
contenido de escopoletina , una cumarina con efectos
antiespasmódicos y sedativos sobre la musculatura
lisa y salicina, un analgésico reconocido.
[4,6].
La corteza de los tallo y raíces es antiespasmódico
[7-10] . Una decocción se utiliza por vía
oral para el tratamiento de menstruaciones dolorosas
o profusas, prolapso uterino, para detener las
contracciones del parto prematuro y para aliviar
los espasmos después del parto (entuertos)
[4, 6, 10]. También en otros dolores cólicos,
como los que afectan las vías biliares
o el broncoespasmo asmático [4,6]. |
Principios activos:
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|
-
Cumarinas
, incluyendo e scopoletin a , escopolina
, y esculetina .
-
Flavonoides ( amentoflavona
).
-
Beta- sitosterol .
-
Glucósidos iridoides
-
Triterpenos y ácidos
triterpénicos
-
Ácidos orgánicos,
incluyendo acético, caprónico
, caprílico , cítrico,
isovalérico , linoleico , málico,
mirístico , oleico, oleanólico
, oxálico, palmítico,
ursólico , valérico.
|
Estructura
química de la Escopoletina |
- Derivados del ácido
hidroxicinámico tales: ácido cafeic
o , clorogénic o e isoclorogénic
o .
- Triterpenos : alfa y beta-
amirina
- Taninos (2%).
- Acido salicílico, Salicina.
Algunos investigadores consideran que la planta
no contiene Salicina y que este principio ha
sido confundido con la Arbutina .
|
| Mecanismo
de acción:
Sus derivados cumarínicos
tienen efecto espasmolítico, por inhibición
de la movilización del Calcio intracelular
y por inhibición de la síntesis
de óxido nítrico. (17,18)
El ácido salicílico y la Salicina
le confieren propiedades analgésicas.
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antiespasmódico
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|
| Indicaciones
1) Tratamiento de cólicos biliares, intestinales,
uterinos, genitourinarios o bronquiales.
2) Dismenorrea
3) Amenaza de aborto o de parto
prematuro.
4) Hemorragias postparto
|
| Dosificación:
2
cápsulas con 350 mg de polvo de Acerola
negra con cada comida. |
| Efectos
adversos:
A las dosis recomendadas no produce
ningún efecto secundario adverso.
Contraindicaciones
No debe ser ingerido por personas alérgicas
a los salicilatos. |
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Referencias
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2: Woodbury RA, 1951,
'The Viburnums ', Drug Standards
19(7-8), pp. 143-152.
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3: Youngken HW, 1932,
'The pharmacognosy , chemistry and pharmacology
of Viburnum III. History, botany and pharmacognosy
of Viburnum opulus L var americanum (Miller)
Ait ', J Am Pharm Assoc 22, pp.
444-62.
|
| |
7. Launert E.
Edible and Medicinal Plants. Hamlyn
9. Uphof J. C. Th. Dictionary of Economic Plants.
Weinheim 1959
12. Ovodova RG, Golovchenko VV, Popov SV. [The
isolation, preliminary study of structure and
physiological activity of water-soluble polysaccharides
from squeezed berries of Snowball tree Viburnum
opulus ] Bioorg Khim . 2000 Jan ;26 (1):61-7.
13. Jarboe CH, Zirvi KA, Schmidt CM. 1-methyl
2 ,3 -dibutyl hemimellitate . A novel component
of Viburnum prunifolium . J Org Chem . 1969 Dec
;34 (12):4202-3.
14. Horhammer L, Wagner H, Reinhardt H. [On new
substances contained in the back of Viburnum prunifolium
L. (American guelder -rose) and Viburnum opulus
L (common guelder -rose)]. Z Naturforsch B. 1967
Jul ;22 (7):768-76.
15. Nicholson JA, Darby TD, Jarboe CH. Viopudial
, a hypotensive and smooth muscle antispasmodic
from Viburnum opulus . Proc Soc Exp Biol Med 1972
Jun;140(2):457-461
 |
16: Biochem Pharmacol
. 2003 Jun 1 ;65 (11):1897-905.
Esculetin inhibits Ras -mediated
cell proliferation and attenuates vascular
restenosis following angioplasty in rats.
Pan SL, Huang YW, Guh JH, Chang YL, Peng
CY, Teng CM.
Pharmacological Institute, College of Medicine,
National Taiwan University, Taipei, Taiwan,
ROC. |
|
The proliferation of vascular smooth muscle
cells ( VSMCs ) induced by injury to the intima
of arteries is an important etiologic factor
in vascular proliferative disorders such as
atherosclerosis and restenosis . Esculetin
, derived from the Chinese herb Artemisia
scoparia , is well known as a lipoxygenase
inhibitor. We have investigated the inhibitory
effects of esculetin on VSMC proliferation
and intimal hyperplasia by balloon angioplasty
in the rat. We determined, using [3H ] thymidine
incorporation and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay, that esculetin inhibited
the proliferation of VSMCs via a lipoxygenase
-independent pathway. Three predominant signaling
pathways were identified to be inhibited by
esculetin : (a) the activation of p42/44 mitogen
-activated protein kinase (MAPK) and the downstream
effectors of c- fos and c- jun immediate early
genes by means of western and reverse transcription-polymerase
chain reaction (RT-PCR) analyses; (b) the
activation of nuclear factor- kappaB (NF-
kappaB ) and activator protein-1 (AP-1), using
the electrophoretic mobility shift assay;
and (c) the activation of phosphoinositide
3-kinase (PI 3-kinase) and cell cycle progression,
by western blot analysis and flow cytometric
detection. Furthermore, esculetin also profoundly
inhibited Ras activation, a shared upstream
event of the above signaling cascades. In
vascular injury studies, intraperitoneal administration
of esculetin significantly suppressed intimal
hyperplasia induced by balloon angioplasty.
We conclude that esculetin blocks cell proliferation
via the inhibition of an upstream effector
of Ras and downstream events including p42/44
MAPK activation, PI 3-kinase activation, immediate
early gene expression, as well as NF- kappaB
and AP-1 activation. It also inhibits intimal
hyperplasia after balloon vascular injury
in the rat, indicating the therapeutic potential
for treating restenosis after arterial injury.
|
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17: Planta Med.
2001 Oct ;67 (7):605-8.
Intracellular calcium mobilization as
a target for the spasmolytic action of scopoletin
.
Oliveira EJ, Romero MA, Silva MS, Silva
BA, Medeiros IA.
Laboratorio de Tecnologia Farmaceutica ,
Universidade Federal da Paraiba , Brazil
.
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The coumarin scopoletin was isolated in a
pure form from the roots of Brunfelsia hopeana
Benth . ( Solanaceae ). In isolated rat aortic
rings, scopoletin (26-520 microM ) inhibited
to approximately the same extent the contractions
induced by a variety of substances, including
phenylephrine , potassium chloride, serotonin
and PGF( 2) (alpha). The effect of the coumarin
on phenylephrine -induced contractions was
not affected by endothelium removal or NO-
synthase blockade by L-NAME (100 microM ).
Scopoletin (78 - 590 microM ) antagonized
in a concentration-dependent manner ( IC(
50) = 300 +/- 20 microM , n = 5), transient
contractions in Ca(2+)-free media induced
by noradrenaline , but not those induced by
caffeine. Also, scopoletin did not interfere
with the refilling of noradrenaline -sensitive
intracellular calcium stores. It is suggested
that the non-specific spasmolytic action of
scopoletin can be attributed, at least in
part, to its ability to inhibit the intracellular
calcium mobilization from the noradrenaline
-sensitive stores. |
18: Planta
Med. 1999 Jun ;65 (5):400-3.
Scopoletin : an inducible nitric
oxide synthesis inhibitory active constituent
from Artemisia feddei .
Kang TH, Pae HO, Jeong SJ, Yoo JC, Choi
BM, Jun CD, Chung HT, Miyamoto T, Higuchi
R.
College of Pharmacy, Wonkwang University,
Iksan , Korea.
Bioassay-guided fractionation of an H2O
extract of Artemisia feddei has furnished
an inducible nitric oxide synthase ( iNOS
) inhibitory coumarin , scopoletin (1) and
one of the inactive sesquiterpenes , achillin
(2). Compound 1 showed inhibition of nitric
oxide (NO) synthesis in a dose-dependent
manner in murine macrophage-like RAW 264.7
cells stimulated with interferon-gamma (IFN-gamma)
plus lipopolysaccharide (LPS). The inhibition
of NO synthesis of 1 was due to suppression
of iNOS mRNA and iNOS protein, as determined
by Northern and Western blotting, respectively.
|
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19: Pharmacol
Res. 1989 Mar-Apr ;21 (2):183-92.
Effects of esculetin (6 ,7 -dihydroxycoumarin)
on guinea-pig tracheal chains in vitro.
Ragazzi E, Froldi G, Fassina
G .
Department of Pharmacology, University of
Padova , Italy .
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Esculetin (6 ,7 -dihydroxycoumarin) was tested
in isolated guinea-pig tracheal chains from
normal and ovalbumin -sensitized animals.
The drug showed a concentration-dependent
relaxant effect, with an EC50 of 60 microM
. Pretreatment with esculetin (30-60 microM
) was not able to reduce the contractile response
induced by either carbachol (0.1 microM ),
histamine (10 microM ), BaCl2 ( 10 mM ) or
K+ ( 80 mM ). Esculetin increased the contraction
evoked by PGF2 alpha and by histamine, but
reduced A23187-induced contraction. Mepacrine
(10 microM ), a phospholipase A2 inhibitor,
reduced the relaxant effect of the lower esculetin
concentrations (3-60 microM ). Indomethacin
(0.1 microM ) increased the relaxation induced
by esculetin (3-10 microM ). In tracheal chains
from ovalbumin -sensitized guinea-pigs, esculetin
(60 microM ) significantly reduced the duration
of the recovery phase after antigen challenge
contraction. In conclusion, in our in vitro
conditions, this natural coumarin derivative
seems to act by interfering with the arachidonic
acid cascade. |
| 20:
Pharmacol Res Commun . 1988 Dec ;20
Suppl 5:83-5.
Anti-inflammatory and peripheral analgesic
activity of esculetin in vivo.
Tubaro A, Del Negro P, Ragazzi
E, Zampiron S, Della Loggia R.
Institute of Pharmacology and Pharmacognosy
, University of Trieste, Italy.
Esculetin determined a reduction in oedema
and granulocyte infiltration in the Croton
oil ear test in vivo. The drug was able
to inhibit Acethylcholine -writhing test
and showed a LD50 of 1450 mg/kg i.p . and
greater than 2000 mg/kg by mouth. In our
experimental conditions, esculetin has an
anti-inflammatory and analgesic effect.
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21: Biochim Biophys
Acta . 1983 Aug 29 ;753 (1):130-2.
Inhibitory effect of esculetin on 5-lipoxygenase
and leukotriene biosynthesis.
Neichi T, Koshihara Y, Murota
S. |
|
Esculetin (6 ,7 -dihydroxycoumarin) showed
inhibitory effects on 5- and 12-lipoxygenases
of cloned mastocytoma cells. The half-inhibition
dose (ID50) for each enzyme was 4 X 10(-6)
and 2.5 X 10(-6) M, respectively. No inhibition
at all, but rather a stimulating effect
on prostaglandin synthesis, was observed,
especially at higher doses of esculetin
. Leukotriene synthesis by mouse mast tumour
cells was also reduced in the presence of
esculetin in parallel with 5-lipoxygenase
inhibition. From these results, esculetin
may be useful as a tool for research on
regulatory mechanisms or physiological functions
of leukotrienes. |
| 22:
Poceedings of the Societa Italiana di
Fitochimica 9th National Congress, May 1998,
Societa Italiana di Fitochimica , Florence
, p 115-6.
Iridoid glucosides from Viburnum
prunifolium and preliminary pharmacological
studies',
Tomassini L, Cometa MF, Palmery
M, Nicoletti M.
In this study it was shown that total V.
prunifolium extract, ethyl acetate, and
butanol fractions inhibited spontaneous
contractions of isolated rat uteri by approximately
50%. Additionally, inhibition of the rise
in tone and reduction of the ampitude of
acetylcholine-induced contractions was observed.
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| 23:
Med Plants Phytother 17(3), pp
123-32.
Criteres de choix d'un extrait
de viburnum , Viburnum prunifolium L., en
fonction de ses actions toniveineuse et
spasmolytique
Balansard G, Chausse D, Boukef
K.
In this study it was reported that a 30%
ethanol extract of V. prunifolium elicited
a spasmolytic activity that was five times
greater than a 60% ethanol extract. It was
concluded that while the spasmolytic activity
was clearly less than that of papaverine
, it was nevertheless significant. |
| 24:
Proceedings of the Society for Experimental
Biology and Medicine, June, 1972, Vol. 110,
No. 2, pp. 457-461
Viopudial , a Hypotensive and
Smooth Muscle Antispasmodic
Nicholson, J. A., Darby, T. D., and
Jarboe , C. H.
The American variety of Viburnum opulus
, native to the northern and eastern United
States , is commonly referred to as the
"Cranberry Bush" or "High Bush Cranberry"
. At this time we wish to report a second
active constituent of V. opulus , a nonalkaloidal
material isolated from plant bark. This
substance has also show striking cardiovascular
effects on the rat, cat and dog, in addition
to antispasmodic effects on in vitro rat
uteri. . In vivo rat experiments showed
hypotensive effects at an iv dose of 250
µg/kg. At 1 mg/kg these effects became
somewhat sustained and the decrease in blood
pressure was accompanied by a decrease in
heart rate. . Summary. The administration
of viopudial a Viburnum opulus component,
produces bradycardia , hypotension, and
some decrease in myocardial contractility.
Experimental evidence indicates that viopudial's
mechanism of action is partly due to its
effects on cholinesterase. In vitro demonstrations
of a competitive inhibitory effect on both
acetylcholinesterase and butyrylcholinesterase
showed viopudial to be relatively weak when
compared to know potent inhibitor, physosgitmine
. Additional mechanistic effects, such as
a direct musculotrophic action, may also
be responsible for the overall activity.
|
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25: Nature. 1966
Nov 19; 212(64): 837.
Uterine Relaxant Properties of Viburnum
Jarboe , C. H., Schmidt C. M.,
Nicholson, J. A., and Zirvi , K. A. |
|
Several species have been mentioned repeatedly
as uterine relaxants and general antispasmodics.
Those most commonly cited are V. opulus
(Cramp Bark) . These results obtained from
know material and uteri in a known state
of oestrus show that there is no doubt as
to the uterine antispasmodic properties
of Viburnum opulus . Our investigations
of the chemistry of Viburnum have been restricted
to the historical examples, V. prunifolium
and V. opulus . Using column and thin layer
chromatography we have isolated from these
two species a minimum of four very active
uterine relaxants and are involved in structural
and mechanistic analyses. The mechanism
studies lead us to postulate that these
substances are not sympathomimetic in action,
but selective uterine relaxants which act
directly on the muscle. |
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