Anti-perimenopausal osteoporosis effects of Erzhi formula via regulation of bone resorption through osteoclast differentiation: A network pharmacology-integrated experimental study was written by Qin, Xiao-yan;Niu, Zi-chang;Han, Xiao-ling;Yang, Yun;Wei, Qiu;Gao, Xiao-xue;An, Ran;Han, Li-feng;Yang, Wen-zhi;Chai, Li-juan;Liu, Er-wei;Gao, Xiu-mei;Mao, Hao-ping. And the article was included in Journal of Ethnopharmacology in 2021.Formula: C16H10O7 The following contents are mentioned in the article:
Erzhi formula (EZF) consists of Ecliptae herba (EH) and Fructus Ligustri Lucidi (FLL) at a ratio 1:1, and constitutes a well-known formula in China that is commonly used for treating menopausal diseases. In this study, we explored the pharmacol. actions and potential mol. mechanisms underlying EZFs action in preventing and treating osteoporosis. The active components and related targets of EZFs anti-osteoporotic effects were predicted by network pharmacol., and functional enrichment anal. was also performed. We then used an osteoporosis model of ovariectomized (OVX) mice to detect the effects of EZF on osteoporosis. The results from network pharmacol. identified a total of 10 active ingredients from EH and 13 active ingredients from FLL that might affect 65 potential therapeutic targets. GO enrichment anal. revealed that EZF affected bone tissue primarily via hormone (particularly estradiol)-related pathways and bone resorption by osteoclast differentiation. KEGG anal. demonstrated that bone-related factors such as Runt-related transcription factor 2 (Runx2), Ca2, estrogen receptor1 (ESR1), androgen receptors (AR), and TNFα served as the primary targets during osteoclastic differentiation. In vivo experiments showed that the formula significantly improved the diminution in estrogen and the subsequent uterine atrophy induced by ovariectomy (P < 0.01 or 0.05), implying that the EZF exerted its actions via regulation of estradiol and the nourishing effects of the uterus in OVX mice. Dual-energy X-ray absorptiometry and micro-CT showed that EZF significantly inhibited bone loss and improved bone micro-architecture by statistically increasing the number of bone trabeculae and decreasing the separation of bone trabeculae in OVX mice (P < 0.01 or 0.05); EZF also inhibited bone loss and enhanced bone-fracture load. Furthermore, we confirmed that EZF reduced the calcium concentrations, augmented protein and mRNA levels for Runx2 in the bone marrow, and reduced PPARγ levels. RANKL-a key downstream regulatory protein of many targets that was referred to in our results of network pharmacol. as being involved in the regulation of osteoclastogenesis-was significantly diminished by EZF; it also elevated OPG content. In addition, we used monocytes of bone-marrow origin to detect the effects of the potential components of EZF on osteoclast differentiation and found that wedelolactone, oleanolic acid, echinocystic acid, luteolin, and luteolin-7-o-glucoside significantly inhibited osteoclast differentiation from monocytes induced by 25 ng/mL MCSF and 50 ng/mL RANKL (P < 0.01 or 0.05). Our present study indicated that EZF significantly inhibited the bone loss induced by OVX in mice by its regulation of estradiol combined with the nourishing effect of the uterus, and that it also attenuated bone resorption by decreasing the RANKL/OPG ratio so as to inhibit osteoclast maturation. This study involved multiple reactions and reactants, such as 1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9Formula: C16H10O7).
1,8,9-Trihydroxy-3-methoxy-6H-benzofuro[3,2-c]chromen-6-one (cas: 524-12-9) belongs to benzofurans derivatives. Many natural or synthetic compounds containing benzofuran skeletons have been found to possess remarkable activity as agrochemicals and pharmaceuticals. As benzofurans are prone to undergo ring opening of the heterocycle, examples of reduction of this type of aromatics by using dissolving metals are rather scarce.Formula: C16H10O7
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem