Zhang Rui, Fan Jifa, Zhang Zimeng, Wang Yongxiang, Dai Wenling, Liu Jihua
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, Jiangsu, China.
Yangtze River Pharmaceutical (Group) C., Ltd, Taizhou, 225321, Jiangsu, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 29. doi: 10.1007/s00210-025-04193-w.
Biling Weitong Granules (BLWTG) is a clinical formula employed for treating epigastric pain, yet its pharmacodynamic components and mechanisms against chronic gastric ulcers (GU) remain inadequately understood. The objective of this study was to investigate the targets and mechanisms of BLWTG and its bioactive components in chronic GU. Chronic GU model was induced in SD rats through acetic acid injection, and administered BLWTG post-induction. The macroscopic ulcer appearance, microscopic histology, mucosal growth, vascular promoting factors, myeloperoxidase, and inflammatory factors in gastric tissue were assessed. Network analysis was used to predict the potential core targets and pathways. Further, bioactive components were screened based on cell model, identified by HPLC-QTOF-MS and validated in vivo. The results showed that BLWTG effectively mitigated pathological damage, achieving a 63.32% ulcer healing rate. Network analysis and experimental verification showed that the effectiveness of BLWTG stemmed from its capacity lower oxidative stress and inflammation, boost antioxidant levels, and promote the synthesis of gastric mucosal protective factors and repair. Further, the primary active fraction of BLWTG was ethyl acetate fraction, which increased the ulcer healing rate to 75.04%. Among the 55 compounds identified in the ethyl acetate fraction of BLWTG, evodiamine, dehydroevodiamine, berberine and tetrahydropalmatine may represent the active components responsible for facilitating the regeneration and repair of GU. In conclusion, BLWTG and its bioactive components significantly promote healing in rat models of chronic GU, providing a scientific basis for further applications of BLWTG in treating chronic GU.
必利胃痛颗粒是一种用于治疗胃脘痛的临床方剂,但其治疗慢性胃溃疡(GU)的药效成分及作用机制尚不清楚。本研究旨在探讨必利胃痛颗粒及其生物活性成分在慢性胃溃疡中的作用靶点和机制。通过向SD大鼠注射乙酸诱导慢性胃溃疡模型,并在诱导后给予必利胃痛颗粒。评估胃组织的宏观溃疡外观、微观组织学、黏膜生长、血管生成因子、髓过氧化物酶和炎症因子。采用网络分析预测潜在的核心靶点和信号通路。此外,基于细胞模型筛选生物活性成分,通过HPLC-QTOF-MS进行鉴定并在体内进行验证。结果表明,必利胃痛颗粒能有效减轻病理损伤,溃疡愈合率达63.32%。网络分析和实验验证表明,必利胃痛颗粒的有效性源于其降低氧化应激和炎症、提高抗氧化水平以及促进胃黏膜保护因子合成和修复的能力。此外,必利胃痛颗粒的主要活性部位为乙酸乙酯部位,其溃疡愈合率提高至75.04%。在必利胃痛颗粒乙酸乙酯部位鉴定出的55种化合物中,吴茱萸碱、去氢吴茱萸碱、小檗碱和延胡索乙素可能是促进慢性胃溃疡再生和修复的活性成分。综上所述,必利胃痛颗粒及其生物活性成分能显著促进慢性胃溃疡大鼠模型的愈合,为必利胃痛颗粒进一步应用于治疗慢性胃溃疡提供了科学依据。