Anti-Menopausal Effects of Cornus officinalis and Ribes fasciculatum Extract In Vitro and In Vivo

Abstract

Natural herbal medicines have been developed for the treatment and prevention of women’s menopausal symptoms. In this study, we investigated the anti-menopausal effects of Cornus officinalis (CO) and Ribes fasciculatum (RF) extracts in 3T3-L1 preadipocytes, MC3T3-E1 preosteoblasts, and COV434 granulosa cells in vitro and ovariectomized (OVX) ddY mice in vivo. Combination treatment of CO and RF extract at 7:3 ratio inhibited lipid accumulation via Plin1 and Adipoq downregulation in a cocktail of dexamethasone, 3-isobutyl-1-methylxanthine, and insulin (DMI)-induced differentiated 3T3-L1 cells. In addition, CO + RF treatment significantly enhanced osteoblastic differentiation, with mineralized nodule formation occurring through the upregulation of osteoblast-inducing markers in osteoblastic MC3T3-E1 cells. Increased production of estradiol and mRNA expression of ERα (ESR1) were observed in androstenedione-induced COV434 granulosa cells treated with the CO + RF extract. In CO + RF-treated mice, fatty hepatocyte deposition and abdominal visceral fat tissues reduced with OVX-induced uterine atrophy. Furthermore, bone mineral density and bone mineral content were significantly enhanced by CO + RF in mouse models of ovariectomy-induced femoral bone loss. Taken together, our findings suggested that CO + RF promoted estrogenic activity and had anti-obesity and anti-osteoporotic effects in vitro and in vivo. Thus, a combination of CO and RF extracts may be a good therapeutic strategy for managing women’s menopausal syndromes.

Antiadipogenic Effects of Mixtures of Cornus officinalis and Ribes fasciculatum Extracts on 3T3-L1 Preadipocytes and High-Fat Diet-Induced Mice

“…These adipogenic-related genes stimulate adipocyte differentiation of 3T3-L1 cells and differentiated adipocytes were apparently by lipid-rich accumulation, which is histologically stained by oil red O [47]. In previous studies, a CO-containing formulation inhibited the expression of Pparg and Cebpa [48] and a mixture of CO and RF extracts reduced ovariectomized (OVX)-induced weight gain in mice [49]. Our results show that CO and RF extracts significantly suppressed the expression of Pparg and Cebpa, which may, in turn, decrease the expression of Fabp4, because Fabp4 is a target gene of Pparg and Cebpa.…”

Efficacy and Safety of Combined Extracts of Cornus officinalis and Ribes fasciculatum for Body Fat Reduction in Overweight Women

“…Combined treatment of CO and RF has become well-known traditional herbal agents during the past decade. Previous studies showed that combined CO and RF extracts had synergistic effects on anti-menopausal syndrome and anti-obesity [ 26 , 27 ]. CO and RF mixture decreased adipocyte differentiation in 3T3-L1 pre-adipocytes, through the downregulation of adipogenic markers such as Adipoq , Fabp4 , Pparg , Srebp1 , and Plin1 [ 26 , 27 ].…”

“…Previous studies showed that combined CO and RF extracts had synergistic effects on anti-menopausal syndrome and anti-obesity [ 26 , 27 ]. CO and RF mixture decreased adipocyte differentiation in 3T3-L1 pre-adipocytes, through the downregulation of adipogenic markers such as Adipoq , Fabp4 , Pparg , Srebp1 , and Plin1 [ 26 , 27 ]. Differentiation of adipocyte is characterized by lipid accumulation [ 33 ], CO and RF mixture also inhibited the number of lipid droplets in the cytoplasm of 3T3-L1 cells.…”

“…Furthermore, CO and RF mixture prevented both obesity murine models including OVX and high-fat diet induced obesity mice, the well-known features of obesity in murine model. Oral administration of CO and RF mixture reduced total body weight, %fat, white adipocyte size and hepatic steatosis, resulting in inhibition of body weight gain in OVX and high-fat diet induced obesity mice [ 26 , 27 ]. These reports support the clinical trial that CO and RF mixture could present anti-obesity effect on human.…”

“…Many studies suggested that combination of natural products presented advantages of synergistic complex effects, compared to single treatments [ 22 , 23 , 24 , 25 ]. Current studies demonstrated that treatment of CO and RF mixture (COEC) enhanced anti-menopausal effects by increasing estrogenic activity and decreasing ovariectomy (OVX) induced weight gain and osteoporosis [ 26 ]. In addition, mixture of CO and RF extracts showed antiadipogenic effects in pre-adipocyte 3T3-L1 cells and high-fat diet (HFD) induced overweight mice [ 27 ].…”