Component-target network and mechanism of Qufeng Zhitong capsule in the treatment of neuropathic pain

• Published in: Journal of ethnopharmacology 2022-01, Vol.283, p.114532-114532, Article 114532
• Main Authors: Liao, Yu-cheng, Wang, Jing-wen, Zhang, Juan-li, Guo, Chao, Xu, Xin-liang, Wang, Kai, Zhao, Chao, Wen, Ai-dong, Li, Rui-li, Ding, Yi
• Format: Article
• Language: English
• Subjects: Animals; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Hyperalgesia - drug therapy; Hyperalgesia - physiopathology; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Myeloid Differentiation Factor 88 - metabolism; Network Pharmacology; Neuralgia - drug therapy; Neuralgia - physiopathology; Neuropathic pain; NF-kappa B - metabolism; Qufeng zhitong capsule; Signal Transduction - drug effects; TLR4/MyD88/NF-κB signaling pathway; Toll-Like Receptor 4 - metabolism
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2021.114532

Qufeng Zhitong capsule (QFZTC) is a traditional Chinese medicine (TCM) clinically used for treating pain. However, the active ingredients of QFZTC and its pharmacological mechanism in the treatment of neuropathic pain (NP) remain unclear. We aimed to identify the active ingredients of QFZTC and reveal its target genes and underlying mechanism of action in NP. High-performance liquid chromatography (HPLC) was used to identify the active ingredients of QFZTC. Network pharmacology analysis was conducted to determine the core targets and pathway enrichment of QFZTC. An NP mice model was established through chronic compression injury (CCI) surgery of the sciatic nerve, while von Frey instrumentation and a thermal stimulator were employed to measure the sensitivity of mice to mechanical and thermal stimuli. Immunofluorescence was used to observe the expression of TLR4 and p-P65 in microglia. Western blotting was used to detect the levels of protein expression of Iba-1, TLR4, MyD88, P65, p-P65, and c-Fos, while ELISA kits were used to detect the release of TNF-α, IL-6, and IL-1β. Seven active ingredients were identified in QFZTC: gallic acid, loganylic acid, syringin, corilagin, loganin, ellagic acid, and osthole. Network analysis identified TLR4, TNF, IL6, IL1β, and c-Fos as core targets, and Toll-like receptors and NF-κB as core signaling pathways. Treatment with QFZTC significantly relieved mechanical allodynia and thermal hyperalgesia in CCI mice models. CCI induced an increase in the expression of TLR4 and p-P65 in microglia, whereas QFZTC dose-dependently reduced the expression of Iba-1, TLR4, MyD88, and p-P65 in the spinal cord. QFZTC inhibited the expression of the c-Fos pain marker and reduced the expression of the TNF-α, IL-6, and IL-1β inflammatory factors. We combined the active ingredients of QFZTC with network pharmacology research to clarify its biological mechanism in the treatment of NP. We demonstrated that QFZTC reduced NP in mice probably through regulating the spinal microglia via the TLR4/MyD88/NF-κB signaling pathway. Hence, QFZTC could be regarded as a potential drug for relieving NP. [Display omitted] •The therapeutic effect of QFZTC against neuropathic pain was studied.•Biomarkers and possible therapeutic targets associated with neuropathic pain were screened out.•QFZTC regulating the TLR4/MyD88/NF-κB pathway in microglia to treat neuropathic pain.•A combined approach of network pharmacology and biological research was applied.