several phytochemical compounds as an antiangiogenic agent in amelioration of endometriosis
In endometriosis a new drug is REVERSATOL
Why anti-angoigenic agent?? It is widely accepted that peritoneal endometriotic lesions develop from endometrial tissue fragments, which are rctrogradlcy shed through the fallopian tubes during menstruation. During the past few years, numerous studies could demonstrate that the establishment and survival of these lesions is crucially dependent on neoangiogensis i.e. Formation of new blood vessels, which ensure their oxygen supply. Accordingly, anti-angiogenic agents of different substance groups are currently discussed as promising candidates for future endometriosis therapy. Besides specific growth factor antagonists, endogenous angiogenesis inhibitors, statins, cyclooxygenase-2 inhibitors and immunomodulators, these antiangiogenic agents also include several phytochemical compounds. The latter ones have been successfully used in traditional medicine without inducing severe side effects.
In endometriosis a new drug is REVERSATOL
Why anti-angoigenic agent?? It is widely accepted that peritoneal endometriotic lesions develop from endometrial tissue fragments, which are rctrogradlcy shed through the fallopian tubes during menstruation. During the past few years, numerous studies could demonstrate that the establishment and survival of these lesions is crucially dependent on neoangiogensis i.e. Formation of new blood vessels, which ensure their oxygen supply. Accordingly, anti-angiogenic agents of different substance groups are currently discussed as promising candidates for future endometriosis therapy. Besides specific growth factor antagonists, endogenous angiogenesis inhibitors, statins, cyclooxygenase-2 inhibitors and immunomodulators, these antiangiogenic agents also include several phytochemical compounds. The latter ones have been successfully used in traditional medicine without inducing severe side effects.
What is
Resveratrol?
Resveratrol is one such
natural phytoalexin, which represents one of the most frequently analysed
phytochemical compounds in life sciences during the last decades. Because resveratrol
exerts a broad spectrum of beneficial effects under various pathological
conditions, it has been suggested as a promising therapeutic agent for the
treatment of cancer as well as several inflammatory, metabolic and
cardiovascular diseases.
Resveratrol is a
polyphenol synthesized by plants following ultraviolet radiation and fungal
infections. Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is found in red
grape skin, Japanese knotweed (Polygonum cuspidatum), peanuts, blueberries and
some other berries. A large amount of resveratrol is produced in the skin of
grapes to protect the plant against fungal diseases and sun damage; therefore,
wine has higher levels of resveratrol compared to other natural food. Overall,
red wine contains small amounts of resveratrol, <1-2 mg/8 ounces of red
wine. However, red wine has more resveratrol than white wine because red wines
are fermented with the grape skins longer than white wines. Hence, many of the
antioxidants including resveratrol that are naturally present in the grape
skins are extracted into the wine. Resveratrol is also present in the seeds and
pomace of grapes.
Resveratrol is a
pleiotropic agent, which dose- dependently suppresses the development of new
blood vessels. Growing evidence indicates that this compound possesses
antineoplastic, anti-inflammatory
and antioxidant
properties. Resveratrol has also been shown to exhibit profound in vitro and in
vivo growtli inhibiting and apoptosis - inducing activities in several
biological systems, cancer cell lines and animal models of carcinogenesis.
These properties have been linked to inhibition of proliferation in association
with cell cycle arrest and, in some systems, with increased apoptotic cell
death. Mechanisms of action of resveratrol further include multiple cellular
targets affecting various signal transduction pathways, including AKT, RPS6KB2
(p70S6K), mitogen-activated protein kinase 1/3 (MAPK1/3; ERK1/2), STAB, MAPK14
(P38), protein kinase C and peroxisome proliferator-activated
receptors (PPARs)-gamma. Importantly, several of these pathways arc relevant to
the pathophysiology of endometriosis.
What are the evidences we have ??
In a study carried out by
Bruner-Tran et al, it was shown that resveratrol reduced development of
experimental endometriosis, as evidenced by a decreased proportion of animals
with endometriotic lesions, a lower number of lesions and a smaller volume of
lesions. These protective effects of resveratrol may be related to various
mechanisms such as reduction of proliferation of endometrial cells, increased
cell death (c.g., apoptosis) and/or reduced ability to attach and to implant.
As the duration of treatment did not matter as far as reduction in number of
lesions or volume was concerned, it is likely that the primary mode of action
of resveratrol may be related to prevention from, or at least reduction of,
implantation of endometrial tissues. In another study, patients who remained
symptomatic while using a continuous regimen of a combined pill containing
drospirenone and ethinyl estradiol, the concomitant use of resveratrol at a
daily dose of 30 mg resulted in a significant reduction in the number of
patients reporting the occurrence of pain. This suggests that the combination
of oral contraceptives with naturally occurring aromatase inhibitors may show
promise for the treatment of endometriosis, particularly in patients who failed
to respond satisfactorily to oral contraceptives alone because of the
persistence of dysmenorrhea-like pain and breakthrough bleeding.
What are the Adverse
Effects of
Reversatolol??
Patients who have blood
disorders, which can cause bleeding, should be monitored by a physician while
taking this product. People undergoing surgery should stop taking resveratrol
two weeks before the surgery and not take it for two weeks after the surgery to
reduce the risk of bleeding. Safety of the same has not been established in
pregnant or lactating women. Resveratrol has mild estrogenic activity and until
more is known, women with cancers and other conditions that are estrogen
sensitive should seek medical advice before taking resveratrol.
Resveratrol is a potent
inhibitor of vascularization in endometriotic lesions. Ihis, most probably,
causes the suppression of lesion growth. Accordingly, resveratrol represents a
promising candidate therapy for future phytochemical treatment of
endometriosis.
Although
a large number of studies show encouraging results, it is still premature to
recommend it as an accepted line of treatment because the dose, the purity and
their possible adverse effects still remain largely unknown. Large
population-based studies are required to establish the recommendation.
Randomized controlled trials to establish doses and drug safety will give the
answers to these questions in future. To date, although resveratrol is widely
used as a nutritional supplement, it has not been approved by the Food and Drug
Administration for any clinical application and its long-term safety has yet to
be proven
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