Pharmacological effects of Erxian Decoction, a Chinese medicinal formula, in relieving menopausal syndrome

Abstract

BACKGROUND: Ovarian aging is an inevitable event since the birth of women. Ovarian aging, together with the senescence of the reproductive axis, will eventually lead women to a transit into menopause, which is defined "after 12 months of amenorrhea following the final menstrual period", according to the STRAW staging system (1). The decrease in ovarian estrogen production is though to related to various menopausal symptoms including hot flash (2), osteoporosis (3), increased risk of cardiovascular diseases (4). Although menopausal syndrome can be relieved by conventional hormone replacement therapy, concerns about the cancer incidence (5) herald a safer yet effective alternative therapy. Erxian Decoction (EXD) has been used for relieving menopausal symptoms for more than fifty years. It is composed of six herbs namely Curculigo orchioides (Hypoxidaceae, rhizome), Epimedium brevicornum (Berberidaceae, whole herb), Morinda officinalis How (Rubiaceae, root), Angelica sinensis (Umbelliferae, root), Phellodendron chinense (Rutaceae bark) and Anemarrhena asphodeloides (Anthericaceae, rhizome). To elucidate the science behind its medical efficacy, intensive effort has been spent by our research group. In this abstract, various pharmacological effects of EXD displayed in vivo or in vitro are discussed. Stimulatory effect of EXD on ovarian estrogen biosynthesis It is found that EXD can increase circulating estrogen level through activation of ovarian aromatase, and thus stimulating ovarian estrogen biosynthesis. Currently, the molecular mechanism of EXD is also being studied on rat ovarian granulosa cell. It is also demonstrated that EXD could also stimulate secretion of estradiol from rat ovarian granulosa cell culture. In twelve-month old female SD-rat fed with EXD, the mRNA level of ovarian aromatase (CYP19) increased significantly, while the serum estradiol level were also significantly elevated, suggesting the stimulatory effect of EXD on, at least, ovarian estrogen biosynthesis (6). Effect of EXD on serum lipid profile In another experiment, the effect of EXD on serum lipid profile has been evaluated. It was demonstrated that EXD could significantly decrease the serum total cholesterol level and serum LDL-cholesterol level. Immunoblotting study revealed that the beneficial effect of EXD on serum lipid profile is at least through up-regulation of hepatic LDL-receptor, a protein responsible for clearance of LDL-cholesterol, and down-regulation of HMG-CoA reductase, a key enzyme for cholesterol synthesis (7) Anti-osteoporotic effect of EXD It is known that the incidence of osteoporosis increased after menopause where circulating estrogen level declines. In our recent study, the anti-osteoporotic effect of EXD has been studied in vitro. It was found that EXD could significantly inhibit the proliferation of RAW264.7, the precursor of osteoclast. On the other hand, EXD could also significantly stimulate the proliferation of hFOB1.19, the human fetal osteoblast cell line. Our results revealed that EXD could increase bone formation and reduce bone resorption through regulating the respective cell proliferation. Results from TRAP staining of RAW264.7 also revealed that EXD could inhibit osteoclastogenesis through inhibition of RAW264.7 differentiation. EXD could also increase the trabecular material bone mineral density at the L2 mid-vertebral body in 12-month old female SD-rat, as revealed by microcomputed tomography, suggesting its anti-osteoporotic property in vivo (8). Anti-oxidative effect of EXD EXD also possess anti-oxidative properties, as revealed by the mRNA level of hepatic anti-oxidative enzymes SOD, CAT and GPx-1 (6). Since aging is thought to relate with oxidative stress, the stimulatory effect of EXD on anti-oxidative enzymes suggests the general anti-aging properties of EXD and merits further study. CONCLUSION: The research of diverse pharmacological effects of EXD in vivo and in vitro has been discussed. With the stimulatory effect of EXD on ovarian estrogen biosynthesis, beneficial effects of EXD on serum lipid profile, anti-osteoporotic properties together with the anti-oxidative effects, it is promising that EXD could be an effective alternative for relieving menopausal syndromes.