Department of Surgery, Jining No. 1 People's Hospital, Jining, 272000, Shandong, China.
Shandong First Medical University, Jinan, 250117, Shandong Province, China.
J Orthop Surg Res. 2023 Aug 28;18(1):629. doi: 10.1186/s13018-023-04121-9.
Neuropathic pain (NP) is the most prevalent form of chronic pain resulting from nerve damage or injury. Despite the widespread use of Duhuo Jisheng decoction (DHJSD) in traditional Chinese medicine (TCM) to treat chronic pain, the mechanism underlying its analgesic action remains unclear.
Using network pharmacology, we obtained DHJSD and NP-related target information from public databases to construct protein-protein interactions (PPI) and compound-target networks based on common target genes. These networks were further analyzed using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). The interaction between molecules was verified through molecular docking using AutoDock Tools software. Additionally, we treated a chronic constriction injury (CCI) rat model with DHJSD and determined the mechanical withdrawal threshold (MWT). We used an enzyme-linked immunosorbent assay kit to determine the levels of inflammatory cytokines. Furthermore, qRT-PCR was employed to analyze ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA expression, and immunofluorescence was used to evaluate changes in microglia.
Our screening of compounds and targets identified 252 potential targets of DHJSD associated with NP. PPI analysis, along with GO and KEGG analyses, revealed that the potential mechanism of DHJSD in NP treatment may be related to inflammatory reactions, the IL-17 signaling pathway, MAP kinase activity, and endocrine activity. Based on molecular docking, the core target showed significant affinity for DHJSD's active components. Moreover, DHJSD treatment repaired the CCI-induced inflammatory reaction in the spinal cord while regulating the expression of ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA. Immunofluorescence results indicated that the active components of DHJSD may regulate microglial M1 polarization to improve neuroinflammation, PPARG may have been involved in the process.
The multi-component, multi-target, and multi-pathway actions of DHJSD provide new insights into its therapeutic mechanism in NP.
神经病理性疼痛（NP）是由神经损伤或损伤引起的最常见的慢性疼痛形式。尽管独活寄生汤（DHJSD）在中医（TCM）中被广泛用于治疗慢性疼痛，但它的镇痛作用机制仍不清楚。
我们使用网络药理学，从公共数据库中获得 DHJSD 和 NP 相关的靶标信息，基于共同靶基因构建蛋白质-蛋白质相互作用（PPI）和化合物-靶标网络。进一步对这些网络进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。利用 AutoDock Tools 软件对分子间的相互作用进行分子对接验证。此外，我们用 DHJSD 治疗慢性缩窄性损伤（CCI）大鼠模型，测定机械性撤足阈值（MWT）。采用酶联免疫吸附测定试剂盒测定炎症细胞因子水平。进一步采用 qRT-PCR 分析 ACHE、NOS2、MAPK3、PTGS2、AKT1 和 PPARG mRNA 表达，免疫荧光法评价小胶质细胞变化。
我们筛选出 DHJSD 与 NP 相关的 252 个潜在靶标。PPI 分析以及 GO 和 KEGG 分析表明，DHJSD 治疗 NP 的潜在机制可能与炎症反应、IL-17 信号通路、MAP 激酶活性和内分泌活性有关。基于分子对接，核心靶标与 DHJSD 的活性成分显示出显著的亲和力。此外，DHJSD 治疗修复了 CCI 诱导的脊髓炎症反应，同时调节 ACHE、NOS2、MAPK3、PTGS2、AKT1 和 PPARG mRNA 的表达。免疫荧光结果表明，DHJSD 的活性成分可能通过调节小胶质细胞 M1 极化来改善神经炎症，PPARG 可能参与了这一过程。
DHJSD 的多成分、多靶点、多途径作用为其治疗 NP 的机制提供了新的见解。
