PHYTOESTROGENS Under the Guidance of, Prepared By, Mrs.Sandhya.M, M.PHARM., Lakshmi Sindhura.A Associate professor. Reg.No.10T21S0107 CMR COLLEGEOF PHARMACY KANDLAKOYA (V), HYDERABAD - 501401
CONTENTS Introduction Estrogen Clinical uses of Estrogens Disadvantages of Estrogens Menopause Phytoestrogens Mechanism of action Advantages Products Conclusion
PHYTOESTROGENS: Plant derived xenoestrogens. Not generated within endocrine system. Also called “DIETARY ESTROGENS”. Structural similarity with Estradiol.
Estrogen: Main sex hormone in women. Essential to the menstrual cycle. Estrone, estradiol, estriol. Contributes to the development of secondary sex characteristics. Important to a woman’s health. Reduces after menopause.
MECHANISM OF ACTION: Readily diffuses across cell membrane. Activate estrogen receptors. ER-a and ER-b. ER-a Uterus, testis, pituitary, ovary, epididymis, and adrenal gland. ER-b Brain, kidney, prostrate, ovary, lung, bladder, intestine, and epididymis.
Menopause: Transition period. Between ages of 45 and 55. Body produces less estrogen and progesterone. Premature menopause Perimenopause Surgical menopause Symptoms: Hot flashes, Osteoporosis, Skin dryness.
Side effects during hormone replacement therapy: Risk of vein clots in legs by 2-3 fold Uterine cancer Breast cancer Heart diseases Abnormal vaginal bleeding Stroke High blood pressure Gallstones.
These adverse effects diverted the attention from conventional estrogens and increased interest in phytoestrogens. Natural and basically derived from food products. However the efficacy of conventional estrogens in treating acute vasomotor and psychometric symptoms is much superior to that of phytoestrogens. The rule of thumb is to use conventional estrogen for alleviation of grater efficacy and phytoestrogens should be used for long-term prevention as they are slow-acting, but safer on extended use.
PHYOESTROGENS Dietary estrogens. ADVANTAGES: Easily broken down not stored in tissues and spend very little time in the body, thus they are unlikely to cause cancer. Exert natural balancing levels in body. The US Institute of health sciences announced that long use of synthetic estrogens increased healthy women’s risk of a sroke by 41%,heart attack by 29%, breast cancer by 24%
STRUCTURE: Large group of substituted natural phenolic compounds. Isoflavones, coumestons, lignans.
FOOD SOURCES: Soy food and flax seed have the highest amount of phytoestrogen. Below is a short list of phytoestrogen food sources. Flax-seed Soy beans Tofu Soy yogurt Sesame seed Flax bread Multigrain bread
EXTRACTION OF PHYTOEsTROGENS FROM FOOD SOURCES: To determine total phytoestrogen content , enzymatic hydrolysis with Aspergillums nigercellulase is carried out. Acidified solvent extraction: Raw soybean seeds with their seed coats are ground, mixed with 2ml 0.1N Hcl and 10ml of Acetonitrile, stirred for 2hrs at room temperature and filtered. The filtrate is taken to dryness under vaccum at a temperature below 300c. The dried material is redesolved and filtered and the filtrate is analysed through HPLC.
EXTRACTION OF LIGNANS: Alkaline extraction of 0.1g of dry food is performed. After extraction, the pH is adjusted to 5-6 with 750μ l of 100%glacial acetic acid and the extract is centrifuged at 4,500g for 10mins at 100c. An aliquot is taken and methanol is evaporated from this at 600c. A 1ml of aliquot is hydrolyzed by addition of Helix pomatia b glucuronidase and incubated over night at 370c. Samples are transferred to HPLC vials for LC-MRM-MS analysis.
MECHANISM OF ACTION: Phytoestrogens display somewhat higher affinity for ER-β compared to ER-α. The key structural elements that enable phytoestrogens to bind with high affinity to estrogen receptors and display estradiol-like effects are: The phenolic ring that is indispensable for binding to estrogen receptor. Low molecular weight similar to estrogens (MW=272).
METABOLISM: The two main isoflavonoids (genistien and diadzen) are present in all soy bean foods either as aglycone or as beta-glycoside(conjugated). These glycosides are readily hydrolyzed to estrogenically active aglycones. Genistien is further metabolized in gut to p-ethyl phenol, diadzein to equol, dihydrodiadzien to o-methylangolensin. Further metabolism of isoflavonoids takes place by conjugating the aglycone with glucouronic acid and to lesser extent sulfuric acid.
Urinary isoflavonoid excretions range from about 0.3-30 μM/day. Though phytoestrogens can be measured in urine, plasma, feces, semen, bile, saliva, and breast milk, the concentration of their metabolites differ widely among individuals. This is due to gut microflora, antibiotic use, gender difference and concamitent dietary intake. Urinary secretions of vegetarians may contain 1000 times higher phytoestrogens than total urinary steroid estrogens
USES: Phytoestrogen supplements have a number of uses. Menopause Osteoporosis Reduces risk of stroke Reduces risk of cancer
Emerita PhytoEstrogen Cream:
Chattem - Rejuvex (Disc), 30 caplets: Rejuvex supplies 500mg of magnesium - essential for the support of strong healthy bones.
PHYTOESTROGEN &IPRIFLAVONES: Use only as directed. Take two capsules daily with a meal or glass of water. Store in a cool, dry place.
CONCLUSION Because of the adverse effects caused by harmone replacement therapy now a days there is diversion in attention from conventional estrogens and increase in interest in phytoestrogens. The great promise of phytoestrogen use is that they are natural and basically derived from food products; they can be successfully used in all stages of menopause, without any serious harmful effects. Today more and more people are turning to these naturally-occurring compounds as an alternative to man-made and potentially dangerous hormone replacement treatments.