Xiaoke Bitong capsule alleviates inflammatory impairment via inhibition of the TNF signaling pathway to against diabetic peripheral neuropathy

• Published in: Phytomedicine (Stuttgart) 2024-09, Vol.132, p.155867, Article 155867
• Main Authors: Tian, Lulu, Yang, Meiqi, Tu, Shanjie, Chang, Kaixin, Jiang, Huanyu, Jiang, Yuwei, Ding, Lu, Weng, Zhiwei, Wang, Yueqiang, Tan, Xiaolong, Zong, Chunxiao, Chen, Buyang, Dou, Xiaobing, Wang, Xiuge, Qi, Xuchen
• Format: Article
• Language: English
• Subjects: Animals; Capsules; Diabetes Mellitus, Experimental - drug therapy; Diabetic Neuropathies - drug therapy; Diabetic peripheral neuropathy; Drugs, Chinese Herbal - pharmacology; Experimental validation; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Male; Mice; Mice, Inbred C57BL; Network Pharmacology; Signal Transduction - drug effects; TNF signaling pathway; Tumor Necrosis Factor-alpha - metabolism; Xiaoke Bitong capsule
• ISSN: 0944-7113; 1618-095X; 1618-095X
• DOI: 10.1016/j.phymed.2024.155867

•We conducted the pharmacological analysis of XBC formula in the treatment of DPN using the UPLC-Q-TOF/MS and molecular docking.•XBC formula prevents nerve injury by hyperglycemia, and reduced inflammation through mediating PI3K and inhibiting the expression of TNF-α in the TNF signaling pathway.•XBC formula showed low toxicity towards the RSC96 cells, suggesting that it was safe for use in the treatment of DPN.•Multiple active compounds within the XBC formula that were effective in treating DPN and warranted further research to fully explore its potential. Xiaoke Bitong capsule (XBC) is a crude herbal compound believed to tonify qi, improve blood circulation, and alleviate blood stasis. It has been used as an herbal formula for the prevention and treatment of diabetic peripheral neuropathy (DPN) under the guidance of traditional Chinese medicine (TCM). However, the pharmacological mechanisms by which XBC ameliorates DPN remain poorly understood. The interaction between pro-inflammatory factors and the activation of tumor necrosis factor (TNF) plays a critical role in the underlying mechanisms of DPN. XBC may protect against DPN through the regulation of the TNF pathway. Many studies show the association between DPN and nerve dysfunction, however, treatment options are limited. To identify specific therapeutic targets and active components of XBC that contribute to its anti-DPN effects, our study aimed to investigate the potential mechanism of action of XBC during the progression of DPN using a system pharmacology approach. An approach involving UPLC-Q-TOF/MS and network pharmacology was used to analyze the compositions, potential targets, and active pathways of XBC. Further, models of streptozocin (STZ) induced mouse and glucose induced RSC96 cells were established to explore the therapeutic effects of XBC. High glucose induced RSC96 cells were pretreated with small interfering RNA (siRNA) to identify potential therapeutic targets of DPN. Seventy-one active compositions of XBC and five potential targets, including mitogen-activated protein kinase 8 (MAPK), interleukin-6 (IL-6), poly-ADP-ribose polymerase-1 (PARP1), vascular endothelial growth factor A (VEGFA), and transcription factor p65 (NF-κB), were considered as the potential regulators of DPN. In addition, the results revealed that the TNF signaling pathway was closely related to DPN. Moreover, DPN contributed to the decreased expressions of PI3K and AKT, increased TNF-α and IL-1β in RSC96 cells, whi