Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

[1]  Jae-Yong Kim,et al.  Anti-Atherosclerotic Effects of Fruits of Vitex rotundifolia and Their Isolated Compounds via Inhibition of Human LDL and HDL Oxidation , 2019, Biomolecules.

[2]  S. Salsano,et al.  Phytoestrogen exposure alters endometrial stromal cells and interferes with decidualization signaling. , 2019, Fertility and sterility.

[3]  H. Hua,et al.  Mechanisms for estrogen receptor expression in human cancer , 2018, Experimental Hematology & Oncology.

[4]  K. Kang,et al.  Beneficial effects of Cirsium japonicum var. maackii on menopausal symptoms in ovariectomized rats. , 2018, Food & function.

[5]  R. Salari,et al.  A review of effective herbal medicines in controlling menopausal symptoms , 2017, Electronic physician.

[6]  M. Gietka-Czernel,et al.  Obesity in menopause – our negligence or an unfortunate inevitability? , 2017, Przeglad menopauzalny = Menopause review.

[7]  Jian Zhang,et al.  A new iridoid glycoside from the fruits of Vitex rotundifolia , 2017, Natural product research.

[8]  R. Lobo.  Hormone-replacement therapy: current thinking , 2017, Nature Reviews Endocrinology.

[9]  R. Liu,et al.  A Review on the Terpenes from Genus Vitex , 2016, Molecules.

[10]  Shery Jacob,et al.  A simple practice guide for dose conversion between animals and human , 2016, Journal of basic and clinical pharmacy.

[11]  Haifei Shi,et al.  Regulation of Estrogen Receptor α Expression in the Hypothalamus by Sex Steroids: Implication in the Regulation of Energy Homeostasis , 2015, International journal of endocrinology.

[12]  Jiang Li,et al.  Molecular mechanisms of casticin action: an update on its antitumor functions. , 2014, Asian Pacific journal of cancer prevention : APJCP.

[13]  P. Vrtačnik,et al.  The many faces of estrogen signaling , 2014, Biochemia medica.

[14]  Songhee Jeon,et al.  The effects of Sutaehwan-Gami on menopausal symptoms induced by ovariectomy in rats , 2012, BMC Complementary and Alternative Medicine.

[15]  J. Moreira,et al.  Increased blood oxidative stress in experimental menopause rat model: the effects of vitamin A low‐dose supplementation upon antioxidant status in bilateral ovariectomized rats , 2012, Fundamental & clinical pharmacology.

[16]  Lu Gao,et al.  [Effects of phytoestrogen, genistein combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized mice]. , 2011, Wei sheng yan jiu = Journal of hygiene research.

[17]  Wendy Y Chen.  Postmenopausal hormone therapy and breast cancer risk: current status and unanswered questions. , 2011, Endocrinology and metabolism clinics of North America.

[18]  K. Rothman,et al.  Hormone Replacement Therapy, Family History, and Breast Cancer Risk Among Postmenopausal Women , 2009, Epidemiology.

[19]  J. Frasor,et al.  Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms , 2009, Menopause.

[20]  H. Burger,et al.  A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project. , 2007, Human reproduction update.

[21]  K. Rahman,et al.  Evaluation of the estrogenic activity of the constituents in the fruits of Vitex rotundifolia L. for the potential treatment of premenstrual syndrome , 2007, The Journal of pharmacy and pharmacology.

[22]  K. Rahman,et al.  Estrogen-like activity of volatile components from Vitex rotundifolia L. , 2007, The Indian journal of medical research.

[23]  H. Jou,et al.  Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women. , 2006, The Journal of nutrition.

[24]  R. Hopkins,et al.  Hormone Therapy in Postmenopausal Women , 2005 .

[25]  S. O. Mueller.  Overview of in vitro tools to assess the estrogenic and antiestrogenic activity of phytoestrogens. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[26]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[27]  M. Wells,et al.  The effect of phytoestrogens on the female genital tract. , 2002, Journal of clinical pathology.

[28]  E. Baracat,et al.  Benefits of Soy Isoflavone Therapeutic Regimen on Menopausal Symptoms , 2002, Obstetrics and gynecology.

[29]  J. Nielsen,et al.  Critical parameters in the MCF-7 cell proliferation bioassay (E-Screen) , 2002, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[30]  Y. Ju,et al.  Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. , 2001, Cancer research.

[31]  M. Biyani,et al.  Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part II--anti-cholesterol activity, effects on osteoporosis & menopausal symptoms. , 2001, Indian journal of experimental biology.

[32]  P. Komesaroff,et al.  Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women , 2001, Climacteric : the journal of the International Menopause Society.

[33]  J. Delgado,et al.  17beta-estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[34]  H. Leffers,et al.  Assaying estrogenicity by quantitating the expression levels of endogenous estrogen-regulated genes. , 2000, Environmental health perspectives.

[35]  S. Haslam,et al.  Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. , 1998, Cancer research.

[36]  C Sonnenschein,et al.  The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. , 1995, Environmental health perspectives.

[37]  B. Hollis,et al.  Skeletal response of ovariectomized rats to low and high doses of 17β-estradiol , 1991 .

[38]  J. Davis,et al.  Adenosine 3',5'-monophosphate in rat uterus: acute elevation by estrogen. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[39]  O. Rønnekleiv,et al.  Physiological consequences of membrane-initiated estrogen signaling in the brain. , 2011, Frontiers in bioscience.

[40]  H. Burger,et al.  Hormonal changes in the menopause transition. , 2002, Recent progress in hormone research.

[41]  D. Williams,et al.  Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. , 1994, The Journal of clinical investigation.