Resveratrol (RSV) (3,5,4'-trihydroxystilbene) is a stilbene found in abundance in berry fruits, peanuts, and some medicinal plants. It has a diverse range of pharmacological activities, underlining the significance of illness prevention and health promotion. The purpose of this review was to delve deeper into RSV's bone-protective properties as well as its molecular mechanisms. Several in vivo studies have found the bone-protective effects of RSV in postmenopausal, senile, and disuse osteoporosis rat models. RSV has been shown to inhibit NF-κB and RANKL-mediated osteoclastogenesis, oxidative stress, and inflammation while increasing osteogenesis and boosting differentiation of mesenchymal stem cells to osteoblasts. Wnt/β-catenin, MAPKs/JNK/ERK, PI3K/AKT, FoxOs, microRNAs, and BMP2 are among the possible kinases and proteins involved in the underlying mechanisms. RSV has also been shown to be the most potent SIRT1 activator to cause stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. RSV may, thus, represent a novel therapeutic strategy for increasing bone growth and reducing bone loss in the elderly and postmenopausal population.
Osteoporosis and periodontitis are two major chronic diseases of postmenopausal women. The association between these two diseases are evident through systemic bone loss and alveolar bone loss. Both postmenopausal osteoporosis and periodontitis impose a considerable personal and socioeconomic burden. Biphosphonate and hormone replacement therapy are effective in preventing bone loss in postmenopausal osteoporosis and periodontitis, but they are coupled with severe adverse effects. Phytoestrogens are plant-based estrogen-like compounds, which have been used for the treatment of menopause-related symptoms. In the last decades, numerous preclinical and clinical studies have been carried out to evaluate the therapeutic effects of phytoestrogens including bone health. The aim of this article is to give an overview of the bidirectional interrelationship between postmenopausal osteoporosis and periodontitis, summarize the skeletal effects of phytoestrogens and report the most studied phytoestrogens with promising alveolar bone protective effect in postmenopausal osteoporosis model, with and without experimental periodontitis. To date, there are limited studies on the effects of phytoestrogens on alveolar bone in postmenopausal osteoporosis. Phytoestrogens may have exerted their bone protective effect by inhibiting bone resorption and enhancing bone formation. With the reported findings on the protective effects of phytoestrogens on bone, well-designed trials are needed to better investigate their therapeutic effects. The compilation of outcomes presented in this review may provide an overview of the recent research findings in this field and direct further in vivo and clinical studies in the future.
Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17β-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κβ ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.