Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling

作者：Shuang Chai, Yanbing Yang, Liwei Wei, Yuju Cao, Jiangtao Ma, Xuxia Zheng, Junyan Teng, Na Qin · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.155516 · 被引用次数：97 · 研究领域：Inflammasome and immune disorders、Bone Metabolism and Diseases、Sphingolipid Metabolism and Signaling

Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated. This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis. This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models. Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured (MC3T3-E1(14) cells were exposed to H2O2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis. Our findings demonstrated that 20 mg/kg Lut, similar to the positive control dr...