Pharmacological mechanisms of Yuxuebi tablet in alleviating neuropathic pain: Insights from network pharmacology, molecular docking, 16S rRNA sequencing, and metabolomics.

Abstract

BACKGROUND: Yuxuebi Tablet (YXBT) is a traditional Chinese patent medicine and is mainly used to treat joint swelling and pain associated with rheumatic arthritis and osteoarthritis. However, to date, no definitive clinical studies have confirmed the efficacy of YXBT for treating neuropathic pain (NP). PURPOSE: To assess the analgesic effects of YXBT on chronic constriction injury (CCI)-stimulated NP in rats and to elucidate the underlying molecular mechanism. METHODS: Network pharmacology and molecular docking were employed to predict the key targets of YXBT in the treatment of NP. A CCI-stimulated rat model of NP was established, and the therapeutic effects of YXBT were evaluated using multiple parameters, including paw withdrawal threshold (PWT), paw withdrawal latency (PWL), histopathological assessment of the sciatic nerve and dorsal root ganglion (DRG), and levels of spinal inflammatory cytokines. The signaling pathways underlying YXBT's effects were further validated by qRT-PCR and immunoblotting. In addition, 16S rRNA sequencing and metabolomics were integrated to investigate the regulatory impact of YXBT on gut microbiota composition and serum metabolites in CCI rats, thereby elucidating its potential mechanisms against NP. RESULTS: YXBT treatment significantly increased PWT and PWL in CCI rats, promoted repair of sciatic nerves and DRG damage, reduced the levels of IL1β, IL6, and TNFα in the lumbar spinal cord, and suppressed activation of the EGFR/PI3K/AKT signaling pathway. Moreover, YXBT reversed metabolic disturbances in phospholipid, amino acid, carnitine, and bile acid pathways, while also modulating the composition and relative abundance of the gut microbiota. CONCLUSION: This study systematically demonstrated the therapeutic effects of YXBT in NP and elucidated its underlying pharmacological mechanism. By regulating gut microbiota, metabolic pathways, and associated metabolites, YXBT provides a scientific basis for its application in NP treatment.