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Study on the analgesic and anti-inflammatory mechanisms of Jingu Zhitong Gel in the treatment of knee osteoarthritis through the IL-17, NGF-TrkA, and COX-2/PGE2 pathways

ABSTRACT: To investigate the therapeutic effects of JGZTG on KOA and elucidate the potential mechanism.Initially, we established a KOA rat model and treated it with JGZTG for 21 days. This study integrated systems pharmacology, transcriptomics, and experimental validation to decipher its mechanisms.After 21days’ treatment, JGZTG significantly increased the pain threshold and the weight bearing on the right foot in KOA rats, reduced inflammatory factor levels of TNFα, IL-6, IL-1β, and PGE2 in the serum and joint lavage fluid of KOA rats with dose dependency. In addition, JGZTG could significantly decrease joint morphology score, improve pathological synovial damage, ameliorate pathological cartilage injury, and alleviate loss of cartilage collagen in KOA models. The results of transcriptomic analysis showed that the anti-inflammatory effect of JGZTG treating KOA might be related to the IL-17 signaling pathway. Further validation via RT-qPCR,WB,and IF of synovial and DRG tissue revealed that JGZTG exhibits pain-relieving and anti-inflammatory effects in KOA, which were potentially achieved by modulating IL-17, NGF-TrkA, and COX-2/PGE2 pathways. These findings provided theoretical support for the mechanisms underlying the therapeutic effects of JGZTG in KOA.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE309646 | GEO | 2026/03/29

REPOSITORIES: GEO

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Project description:OBJECTIVE: To observe the clinical efficacy and safety of Yiqi Yangxue formula (YQYXF) on knee osteoarthritis (KOA), and to explore the underlying therapeutic mechanism of YQYXF through endogenous differential metabolites and their related metabolic pathways.METHODS: A total of 61 KOA patients were recruited and divided into the treatment group (YQYXF, 30 cases) and the control group (celecoxib, Cxb, 31 cases). Effects of these two drugs on joint pain, swelling, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) were observed, and their safety and adverse reactions were investigated. In animal experiments, 63 SD rats were randomly divided into normal control (NC) group, sham operation (sham) group, model (KOA) group, Cxb group, as well as low-dose (YL), medium-dose (YM), and high-dose groups of YQYXF (YH). The KOA rat model was established using a modified Hulth method. Ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS)-based metabolomics technology was used to analyze the changes of metabolites in plasma samples of rats. Comprehensive (VIP) > 1 and t-test p < 0.05 conditions were used to screen the disease biomarkers of KOA, and the underlying mechanisms of YQYXF were explored through metabolic pathway enrichment analysis. The related markers of YQYXF were further verified by ELISA (enzyme-linked immunosorbent assay).RESULTS: YQYXF can improve joint pain, swelling, range of motion, joint function, Michel Lequesen index of severity for osteoarthritis (ISOA) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, ESR, and CRP. No apparent adverse reactions were reported. In addition, YQYXF can improve cartilage damage in KOA rats, reverse the abnormal changes of 16 different metabolites, and exert an anti-KOA effect mainly through five metabolic pathways. The levels of reactive oxygen species (ROS) and glutathione (GSH) were significantly decreased after the treatment of YQYXF.CONCLUSION: YQYXF can significantly improve the clinical symptoms of KOA patients without obvious adverse reactions. It mainly improved KOA through modulating lipid metabolism-related biomarkers, reducing lipid peroxidation and oxidative stress.

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Study on the analgesic and anti-inflammatory mechanisms of Jingu Zhitong Gel in the treatment of knee osteoarthritis through the IL-17, NGF-TrkA, and COX-2/PGE2 pathways

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