Integrated Serum Metabolomics and Network Pharmacology to Reveal the Interventional Effects of Quzhi Decoction against Osteoarthritis Pain.

Objectives: Chronic pain, the main symptom of knee osteoarthritis (OA), remains the primary reason for decreased functional capacity. Quzhi decoction, a TCM prescription, is effective in treating chronic pain in OA, but the potential mechanisms require further exploration. Methods: An anterior cruciate ligament transection (ACLT) rat model was established, and pain-like behavior was evaluated. Metabolomics analysis of serum samples was performed to identify differential metabolites, and network pharmacology was used to identify potential targets of Quzhi decoction for the treatment of OA. Finally, we constructed a comprehensive network of serum metabolomics and network pharmacology. At the same time, the obtained key targets were verified by molecular docking. Results: Quzhi decoction was shown to attenuate pain-like behavior and joint inflammation in OA rats. Through serum metabolomics, thirty potentially significant metabolites were found to be involved in the therapeutic effects of Quzhi decoction against OA pain. According to network pharmacology, 107 active drug components were matched with 115 disease targets, which was partly consistent with the metabolomics findings. Further analysis focused on 6 key targets, including CYP3A4, PLA2G4A, PTGS1, PTGS2, TYR, and ALOX5, and their associated core metabolites and pathways. Molecular docking results showed that the related targets had high affinity with the active pharmaceutical ingredients in Quzhi decoction. Conclusion: The effect of Quzhi decoction on OA pain may be related to the inhibition of joint inflammation, mainly through disturbing arachidonic acid metabolism, tyrosine metabolism, and leukotriene metabolism. Further systematic molecular biology experiments are needed to verify the accurate mechanism.