ArticleFrontiers in microbiology2026
Sijing Pill modulates PGE2/EP4/PI3K-AKT pathway via gut-bone axis to treat postmenopausal osteoporosis.
Article in Frontiers in microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Postmenopausal osteoporosis (PMOP) represents a substantial clinical burden for aging women worldwide. Existing pharmacotherapies are frequently constrained by suboptimal efficacy, poor adherence, and adverse effects, underscoring the need for superior treatment alternatives. The Sijing Pill (SJP) has shown potential in alleviating bone loss in PMOP. However, the fundamental mechanisms underlying its therapeutic effects remain incompletely elucidated, which has impeded its clinical translation and rational application. Methods: The therapeutic effect of SJP on PMOP was first evaluated in ovariectomized (OVX) rat models using hematoxylin and eosin (H&E) staining, micro-computed tomography (μCT), and immunohistochemistry. To investigate the mechanisms, we employed an integrated strategy that combined network pharmacology, molecular docking and dynamics simulations, 16S rRNA sequencing, as well as non-targeted metabolomics coupled with MetOrigin analysis. The key predictions from these analyses were subsequently validated by Western blot and immunohistochemistry. Results: This research confirms that SJP treatment significantly alleviates abnormal weight gain and bone structural degeneration in OVX model mice. Employing an integrated multi-omics strategy, we elucidated a dual mechanism underlying the efficacy of SJP. This mechanism involves the concurrent modulation of the arachidonic acid-PGE2 metabolic axis, which ameliorates osteometabolic inflammation, alongside the remodeling of the gut microbiota, as evidenced by a decreased Conclusion: Sijing Pill modulates the PGE2/EP4/PI3K-AKT signaling pathway via the gut-bone axis to aid in alleviating PMOP.
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