OBJECTIVE: The compounds, targets, and molecular mechanisms of YSGSF in the treatment of PMOP were investigated using broad-spectrum target metabolomics from plants, combined with network pharmacology and animal studies, leading to a discussion on a novel approach to understanding YSGSF\'s action in PMOP treatment.
METHODS: Using ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) within a comprehensive targeted metabolomics framework, the active constituents of YSGSF were identified. This, alongside network pharmacology and molecular docking, facilitated the identification of critical signaling pathways and targets pertinent to YSGSF\'s therapeutic effect on PMOP. Subsequently, an animal model for PMOP was developed. Following intervention grouping, rats\' weight changes were recorded; serum bone metabolic factors were assessed via ELISA; bone microstructure was examined using HE staining and Micro-CT; and key signaling pathway proteins and genes were analyzed through immunohistochemistry to validate YSGSF\'s potential mechanism in PMOP treatment.
RESULTS: A total of 84 main active components of YSGSF were identified. The key signaling pathways affected by YSGSF in the treatment of PMOP were the TNF and IL-7 signaling pathways, closely related to TNF-α, IL-1β, c-jun and other protein targets. The results of animal experiments showed that YSGSF could downregulate the expression of TNF-a, IL-1β and c-Jun proinflammatory factors by regulating the TNF and IL-7 signaling pathways and regulate the inflammatory response, osteocyte differentiation and apoptosis to control the development of PMOP.
CONCLUSIONS: YSGSF activates the TNF-α and IL-7 signaling pathways in PMOP rats, reducing TNF-α and IL-1β levels, the c-Jun inflammatory response, and osteocyte differentiation and apoptosis, thus playing a significant role in treating PMOP.
目的:化合物,目标,利用植物广谱靶代谢组学研究了YSGSF治疗PMOP的分子机制,结合网络药理学和动物研究,引发了关于理解YSGSF在PMOP治疗中作用的新方法的讨论。
方法:在全面的靶向代谢组学框架内,使用超高效液相色谱与三重四极杆线性离子阱串联质谱(UPLC-QTRAP-MS/MS),鉴定了YSGSF的活性成分。这个,除了网络药理学和分子对接,有助于鉴定与YSGSF对PMOP的治疗效果相关的关键信号通路和靶标。随后,开发了用于PMOP的动物模型。干预分组后,记录大鼠体重变化;通过ELISA评估血清骨代谢因子;使用HE染色和Micro-CT检查骨微结构;通过免疫组织化学分析关键信号通路蛋白和基因,以验证YSGSF在PMOP治疗中的潜在机制。
结果:共鉴定出84种YSGSF的主要活性成分。YSGSF治疗PMOP的关键信号通路是TNF和IL-7信号通路,与TNF-α密切相关,IL-1β,c-jun和其他蛋白质靶标。动物实验结果表明,YSGSF可以下调TNF-α的表达,IL-1β和c-Jun促炎因子通过调节TNF和IL-7信号通路而调节炎症反应,成骨细胞分化和凋亡控制PMOP的发展。
结论:YSGSF激活PMOP大鼠的TNF-α和IL-7信号通路,降低TNF-α和IL-1β水平,c-Jun炎症反应,骨细胞分化和凋亡,因此在治疗PMOP方面发挥了重要作用。