基于网络药理学与实验验证探讨土家药大风藤醇提物干预L-精氨酸诱导急性胰腺炎的机制研究

Based on network pharmacology and experimental verification, the intervention of Galevine extract of Tujia medicine in L-arginine-induced acute pancreatitis through the pyrosis pathway of NLRP3/caspase-1/GSDMD cells was investigated

关键词:  急性胰腺炎  NLRP3  Caspase-1  GSDMD  细胞焦亡

Key words:  acute pancreatitis  NLRP3  Caspase-1  GSDMD  Cell pyroptosis

摘要:

目的 基于网络药理学与实验验证探讨土家药大风藤醇提物干预L-精氨酸诱导的急性胰腺炎大鼠的作用和机制。方法 通过文献检索获取大风藤醇提物的主要化学成分,使用多重数据库分析预测大风藤醇提物的药理机制。与此同时,我们将小鼠随机分成4组,每组8只,分别为空白对照组、SAP模型组和大风藤低剂量(15mg/kg)、高剂量(30mg/kg)组,通过大体标本与组织病理检查、生化检查以及分子生物学检查验证大风藤干预L-精氨酸诱导急性胰腺炎的药效及药理机制。结果 大风藤醇提物调治急性胰腺炎的核心活性成分为木兰碱、木兰花碱、木防己碱等,核心靶点有DRD2、SLC6A3、BCHE等,GO功能富集分析得到GO条目2093个(P＜0.05),其中生物过程(BP)条目1799个,细胞组成(CC)条目176个,分子功能(MF)条目118个。KEGG通路富集分析显示大风藤醇提物调治急性胰腺炎的通路主要作用于NOD样受体信号通路、PI3K-Akt信号通路等。在动物实验中,大风藤醇提物组干预组的胰腺评分和胰腺长度均降低,组织病理学检测细胞炎症浸润情况改善。同时,大风藤醇提物能降低NLRP3的表达水平,减少Caspase-1的激活和GSDMD-N的生成,抑制炎性物质(IL-1β、IL-18)的释放,从而抑制了细胞焦亡。结论 大风藤醇提物对L-精氨酸诱导的急性胰腺炎小鼠有治疗作用,其机制可能是与通过调控细胞焦亡,抑制炎性因子的释放有关。

Abstract:

ABSTRACT: OBJECTIVE Through the utilization of network pharmacology and experimental validation, the aim is to investigate the impact and mechanism of the alcohol extract from the indigenous medicine Caulis Caulis Caulis in disrupting L-arginine induced acute pancreatitis in rats.METHODS The objective of this study is to identify the primary chemical components of the alcohol extract of Tripterygium wilfordii through a thorough literature review and utilize various databases to predict the pharmacological mechanism of the extract. Additionally, we conducted an experiment using mice, dividing them into four groups including a control group, SAP model group, and low and high dose groups of Caulis Caulis. The aim was to assess the efficacy and pharmacological mechanism of Caulis Caulis in treating L-arginine induced acute pancreatitis, which was evaluated through gross specimen and histopathological, biochemical, and molecular biological analyses.RESULTS The primary active constituents of the alcohol extract derived from Caulis Clematis for the treatment of acute pancreatitis are magnolianine, magnolianine, and tetrandrine. The key targets of this treatment include DRD2, SLC6A3, and BCHE. Upon conducting GO function enrichment analysis, a total of 2093 GO entries (P<0.05) were obtained, consisting of 1799 biological process (BP) entries, 176 cell composition (CC) entries, and 118 molecular function (MF) entries.The results of the KEGG pathway enrichment analysis revealed that the alcohol extract from Caulis Cauliforme exerts its regulatory effects on acute pancreatitis primarily through the NOD-like receptor signal pathway and the PI3K-Akt signal pathway. In animal experiments, it was observed that the pancreatic score and pancreatic length decreased in the intervention group treated with the alcohol extract of Tripterygium wilfordii, and there was a noticeable improvement in the histopathological detection of inflammatory cell infiltration.Simultaneously, the alcoholic extract derived from Caulis Caulis Caulis has the ability to diminish the expression level of NLRP3, curtail the activation of Caspase-1 and the generation of GSDMD-N, and impede the release of inflammatory agents (IL-1 β、 IL-18), thereby hindering cellular apoptosis.CONCLUSION The therapeutic potential of the ethanol extract derived from Caulis Caulis Caulis has been demonstrated in the context of L-arginine induced acute pancreatitis in mice. The underlying mechanism of this effect is likely associated with the regulation of cell apoptosis and the inhibition of inflammatory factor release.