Hormonal regulation of endometriosis and clinical significance

Worldwide almost 10% of reproductive-aged women are affected by endometriosis and suffer from dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. Endometriosis is a gynecological condition in which endometrial cells are deposited outside the uterine cavity and eventually develop into functional endometrial glands and stroma. It is an estrogen-dependent disease and is critically modulated by other hormones of the reproductive system. Estrogen promotes the cell survival and pro-inflammatory roles for both endometrial epithelial and stromal cells. Overexpression of ER-β promotes invasion of endometriotic lesions as well as epithelial-mesenchymal transition. Moreover, estrogen stimulates the production of prostaglandin E2 (PGE2), which supports angiogenesis in the ectopic lesions. Progesterone counteracts estrogen and inhibits the growth of the endometrial glandular cells. Progesterone resistant endometrial cells confer apoptotic-resistance and aggravate disease condition. Oxytocin stimulates the contraction of uterine muscles by upregulating PGF2α secretion via calcium-mediated pathways leading to dysmenorrhea in endometriosis. On the contrary, gonadotropin and its receptor produce amenorrhea by inducing mitochondrial apoptosis and reducing angiogenesis. Scientists are now exploring these hormone-dependent pathologies of endometriosis to develop anti-endometriotic drugs, which mostly include androgen-based drugs and/or potential estrogen inhibitors. This review highlights the role of some important hormones e.g. estrogen, progesterone, prostaglandin, oxytocin, gonadotropin and melatonin in endometriosis progression and their pharmaceutical potentials.

Importance of Neem Leaf: An insight into its role in combating diseases.

The neem (Azadirachta indica A. Juss) is a tropical evergreen tree (Fam. Meliacae; Subfam. Melioideae) traditionally well known for its medicinal value. Beneficialt effects of different parts of neem are attributed to its biologically active principle ‘Azadirachtin’. Apart from Indian subcontinent, neem is widely used in African countries as therapeutics, preservatives and insecticides. Neem leaves, natural source of flavonoids, polyphenols, isoprenoids, sulphurous and polysaccharides, play important role in scavenging the free radical and subsequently arresting disease pathogenesis. Considerable research has gone into neem for developing cost effective and non-toxic products. The present review has compiled different phytochemicals isolated from neem leaves, methods of extraction and their therapeutic use in preventing several diseases. Here, we highlighted the mechanism of anti-inflammatory and antioxidant activity of neem leaf that underscores the disease through regulation of physiological responses. Also, multiple roles of neem leaf and commercial use of neem formulation as an alternative in paving a frontier in the field of drug discovery are discussed.