XiaoRong Meng,Dandan Meng,Chenhui Xiang,Lingling Pu,Xiaofei Yin,Jing Yang
Objective Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP. Methods A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques—including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA—were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects. Results Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355. Conclusion Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.
Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-β (Aβ) and phosphorylation of tau were analyzed. The expression levels of insulin-like growth factor-1 (IGF-1) pathway-related proteins, such as cAMP response element-binding protein (CREB), were detected. Meanwhile, gut microbiota composition was evaluated. Our results showed that Gas treatment significantly improved cognitive deficits and Aβ deposition in APP/PS1 mice. Moreover, Gas treatment increased the level of Bcl-2 and decreased level of Bax and ultimately inhibited neuronal apoptosis. Gas treatment markedly increased the expression levels of IGF-1 and CREB in APP/PS1 mice. Moreover, Gas treatment improved abnormal composition and structure of gut microbiota in APP/PS1 mice. These findings revealed that Gas actively participated in regulating the IGF-1 pathway to inhibit neuronal apoptosis via the gut–brain axis and that it can be considered a new therapeutic strategy against Alzheimer’s disease.
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