Zheng Yongfei, Liu Shuang, Mao Jiale, Li Tao, Wu Songquan, Zhang Hongliang, Fu Xin, Lei Houxing, Ye Qiaoyong, Wu Shaochang, Zhang Xiaoqin
Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Lishui, Zhejiang, 323000, China.
School of Medicine, Lishui University, Lishui, Zhejiang, 323000, China.
J Ethnopharmacol. 2025 Sep 25;353(Pt A):120334. doi: 10.1016/j.jep.2025.120334. Epub 2025 Jul 31.
The main ingredient of the Huoxiang Shihu Chinese Medicine Formula (HS) is Chimonanthus salicifolius H. It is the first medicine of the She ethnic group. HS is a classical prescription for treating alcoholic gastritis, although its therapeutic mechanism remains uncertain.
The study aimed to elucidate the therapeutic mechanism of HS in alcoholic gastritis through network pharmacology and experimental validation.
A mouse model of alcohol-induced gastritis was established and treated with oral HS decoction at doses of 1 g/kg, 2.5 g/kg, and 5 g/kg for two consecutive weeks. Gastric mucosal protection was evaluated by hematoxylin and eosin (H&E) staining, quantification of inflammatory markers, ELISA assays, and immunohistochemistry to assess oxidative stress levels. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis identified chemical constituents in the HS formula. Potential targets were identified via network pharmacology and subsequently confirmed using immunohistochemistry and Western blot analysis. The binding energy of key active substances and core proteins in HS was initially determined through molecular docking.
HS administration significantly alleviated mucosal pathology by reducing inflammatory cytokine levels, enhancing superoxide dismutase (SOD) and catalase (CAT) activities, and decreasing malondialdehyde (MDA) and nitric oxide (NO) concentrations. In vitro, serum containing HS reduced intracellular ROS levels and promoted cell migration and proliferation while modulating oxidative stress-related markers. A total of 51 compounds were identified from HS, with the HIF-1α/VEGF axis emerging as the core mechanism. Experimental validation confirmed that HS inhibited the HIF-1α, VEGF, and VEGFR2 expression, regulated oxidative stress indicators (NO, MDA, SOD, CAT), and reduced inflammatory cytokines including TNF-α, IL-6, and IL-1β. The molecular docking results indicated that diosmin in HS had the highest binding energy with VEGFR2 protein, which was -10.6 kcal/mol, and it might be the drug substance for HS to exert anti-alcoholic gastritis.
HS protects against alcohol-induced gastric mucosal injury by inhibiting oxidative stress and inflammatory responses through modulation of the HIF-1α/VEGF axis.
藿香石胡中药配方（HS）的主要成分是柳叶蜡梅。它是畲族的第一味药。HS是治疗酒精性胃炎的经典方剂，但其治疗机制尚不确定。
本研究旨在通过网络药理学和实验验证阐明HS治疗酒精性胃炎的机制。
建立酒精性胃炎小鼠模型，连续两周分别给予1 g/kg、2.5 g/kg和5 g/kg剂量的HS水煎剂口服治疗。通过苏木精-伊红（H&E）染色、炎症标志物定量、酶联免疫吸附测定（ELISA）和免疫组织化学评估胃黏膜保护作用，以评估氧化应激水平。液相色谱-质谱联用（LC-MS/MS）分析鉴定HS配方中的化学成分。通过网络药理学确定潜在靶点，随后使用免疫组织化学和蛋白质印迹分析进行确认。最初通过分子对接确定HS中关键活性物质与核心蛋白的结合能。
给予HS可通过降低炎症细胞因子水平、增强超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及降低丙二醛（MDA）和一氧化氮（NO）浓度，显著减轻黏膜病理变化。在体外，含HS的血清可降低细胞内活性氧水平，促进细胞迁移和增殖，同时调节氧化应激相关标志物。从HS中总共鉴定出51种化合物，缺氧诱导因子-1α/血管内皮生长因子（HIF-1α/VEGF）轴成为核心机制。实验验证证实，HS可抑制HIF-1α、VEGF和血管内皮生长因子受体2（VEGFR2）的表达，调节氧化应激指标（NO、MDA、SOD、CAT），并降低包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）在内的炎症细胞因子。分子对接结果表明，HS中的地奥司明与VEGFR2蛋白的结合能最高，为-10.6千卡/摩尔，它可能是HS发挥抗酒精性胃炎作用的药物成分。
HS通过调节HIF-1α/VEGF轴抑制氧化应激和炎症反应，从而预防酒精诱导的胃黏膜损伤。
