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

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.