Yao Yi, Zhong Qiuling, Zhong Yanping, Gao Zixin, Zhou Bo, Lu Chun, Zheng Li, Yin Feiying, Tan Manli
Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.
Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):903-918. doi: 10.1007/s00210-024-03324-z. Epub 2024 Aug 1.
To study the pharmacological effects and mechanisms of phlorizin in the treatment of osteoarthritis (OA) through network pharmacological analysis, molecular docking, and experimental validation. First, we screened out the relevant targets related to phlorizin and OA from the public database. The key targets, biological processes, and signaling pathways of phlorizin against OA were identified by protein-protein interaction (PPI) network, Gene Ontology (GO), and Encyclopedia of Kyoto Genes and Genomes (KEGG) pathway enrichment analysis. Subsequently, molecular docking was performed to predict the binding activity between phlorizin and key targets. Finally, we evaluated the effects of phlorizin on hydrogen peroxide-induced OA in rats and validated its possible mechanism of action based on the findings of the network pharmacology analysis. Network pharmacology revealed a total of 235 cross-targets involved in the treatment of OA. Phlorizin's anti-OA effect was found to be primarily mediated through oxidoreductase activity, with JAK-STAT and NF-κB signaling pathways playing a regulating role, according to pathway enrichment analysis. Phlorizin demonstrated a strong affinity for NF-κB1 targets through molecular docking. Moreover, in vitro experiments demonstrated that phlorizin could enhance intracellular antioxidant enzyme activities with good ROS scavenging ability and significantly reduce the expression of NF-κB1 and inflammatory cytokines. Phlorizin can inhibit the progression of OA. The potential underlying mechanism involves inhibiting the NF-κB pathway to reduce inflammation and promote intracellular antioxidant action.
通过网络药理学分析、分子对接和实验验证，研究根皮苷治疗骨关节炎（OA）的药理作用及机制。首先，我们从公共数据库中筛选出与根皮苷和OA相关的靶点。通过蛋白质-蛋白质相互作用（PPI）网络、基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，确定了根皮苷抗OA的关键靶点、生物学过程和信号通路。随后，进行分子对接以预测根皮苷与关键靶点之间的结合活性。最后，我们评估了根皮苷对过氧化氢诱导的大鼠OA的影响，并根据网络药理学分析结果验证其可能的作用机制。网络药理学显示共有235个交叉靶点参与OA的治疗。通路富集分析表明，根皮苷的抗OA作用主要通过氧化还原酶活性介导，JAK-STAT和NF-κB信号通路起调节作用。通过分子对接，根皮苷对NF-κB1靶点表现出较强的亲和力。此外，体外实验表明，根皮苷可增强细胞内抗氧化酶活性，具有良好的ROS清除能力，并显著降低NF-κB1和炎性细胞因子的表达。根皮苷可抑制OA的进展。潜在的机制可能是通过抑制NF-κB通路来减轻炎症并促进细胞内抗氧化作用。
