Compound of Cynanchum wilfordii and Humulus lupulus L. Ameliorates Menopausal Symptoms in Ovariectomized Mice

Cynanchum wilfordii and Humulus lupulus L. have been used for their various pharmacological properties in South Korea as a traditional medicine or health functional food, respectively, and their intake may relieve menopausal symptoms. The purpose of current study was to determine the effect of compound of Cynanchum wilfordii and Humulus lupulus L. (CWHL) in menopausal symptoms of ovariectomized (OVX) mice. OVX mice received CWHL or caudatin (an active ingredient of CWHL) once daily for 7 weeks. Values for hypothalamic serotonin (5-HT), dopamine, norepinephrine, estrogen receptor (ER)-β, 5-HT1A, and 5-HT2A were significantly enhanced, while value for hypothalamic monoamine oxidase A was reduced in CWHL and caudatin groups compared with the OVX group. CWHL and caudatin significantly reduced tail skin temperature and rectal temperature of OVX mice through partial recovering of the levels of serum estrogen, nitric oxide, follicle-stimulating hormone, luteinizing hormone, and receptor-activator of the NF-κB ligand (RANKL). Moreover, CWHL and caudatin improved bone mineral density via decreasing levels of serum RANKL, tartrate-resistant acid phosphatase, and collagen type 1 cross-linked N-telopeptide and improving levels of serum alkaline phosphatase, osteoprotegerin, and osteocalcin compared with the OVX group without adverse effects such as dyslipidemia. CWHL increased uterine ER-β levels but did not change uterus and vaginal weights. Taken together, the results indicate that CWHL may relieve menopausal symptoms by controlling depression-, hot flashes-, and osteoporosis-associated biomarkers. Therefore, we propose that CWHL might be a safe and potential candidate for management of menopause as a health functional food.