Shen Mengyi, Wang Chunxiao, Zhou Jiapei, Wang Jing, Xiang Hongjie
The First Affiliated Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
College of Traditional Chinese Medicine, Shandong Second Medical University, Weifang, China.
Comb Chem High Throughput Screen. 2025 Aug 4. doi: 10.2174/0113862073377282250716063813.
Chronic atrophic gastritis (CAG) is an important stage in the occurrence and development of gastric cancer, and the morbidity of CAG is increasing year by year. Qilianshupi Decoction (QLSP) is a Chinese herbal compound which has been proved to reverse CAG, but its mechanism remains unknown. We wanted to identify the main components of QLSP by mass spectrometry and liquid phase analysis, and investigate their potential pathways for CAG treatment in combination with network pharmacology.
The main active components of QLSP were identified by liquid chromatography and mass spectrometry. Combined with network pharmacology, the targets where the drugs may act were identified and verified by animal experiments. Rats were randomly divided into control group, model group, QLSP low-dose group, QLSP medium-dose group, QLSP high-dose group and Weifushun group. Rat CAG model was prepared by "N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) + ethanol intragastric + ranitidine feed". After the test, gastric tissues were taken for pathological staining and immunohistochemistry.
We identified 51 prototype components of QLSP and found that QLSP treatment of CAG was closely related to p53. In animal experiments, CAG results in the decrease of Ecadherin and the increase of N-cadherin, Vimentin, p53, SMAD2 and TGF-β (p＜0.05). Both QLSP and Weifuchun can increase E-cadherin and decrease N-cadherin, Vimentin, p53, SMAD2 and TGF-β (p＜0.05).
QLSP, a traditional Chinese medicine formula with multi-component and multitarget characteristics, has been shown in our study to effectively regulate key EMT (epithelialmesenchymal transition) markers and their upstream/downstream regulators. In animal experiments, QLSP successfully reversed the EMT process in CAG model rats. This finding provides new therapeutic targets for CAG treatment, though several challenges remain in clinical translation: First, rat CAG models differ from human CAG in pathological features and disease progression, and species-specific physiological and metabolic variations may limit the extrapolation of these findings. Second, network pharmacology analysis identified IL-6, alongside TP53, as another critical target of QLSP in CAG intervention. Therefore, future studies should further clarify the molecular mechanisms by which QLSP modulates EMT via IL-6-related pathways and validate its efficacy through well-designed clinical trials, ultimately providing a comprehensive understanding of QLSP's therapeutic potential in CAG.
QLSP inhibits epithelial-mesenchymal transition (EMT) in gastric mucosal epithelial cells and prevents CAG, possibly by regulating p53/TGF-β signaling pathway.
慢性萎缩性胃炎（CAG）是胃癌发生发展的重要阶段，且CAG的发病率逐年上升。芪连舒痞汤（QLSP）是一种已被证明可逆转CAG的中药复方，但具体机制尚不清楚。我们希望通过质谱和液相分析确定QLSP的主要成分，并结合网络药理学研究其治疗CAG的潜在途径。
采用液相色谱和质谱法鉴定QLSP的主要活性成分。结合网络药理学，确定药物可能作用的靶点，并通过动物实验进行验证。将大鼠随机分为对照组、模型组、QLSP低剂量组、QLSP中剂量组、QLSP高剂量组和胃复春组。采用“N-甲基-N'-硝基-N-亚硝基胍（MNNG）+乙醇灌胃+雷尼替丁喂养”制备大鼠CAG模型。实验结束后，取胃组织进行病理染色和免疫组化。
我们鉴定出QLSP的51种原型成分，并发现QLSP治疗CAG与p53密切相关。在动物实验中，CAG导致E-钙黏蛋白减少，N-钙黏蛋白、波形蛋白、p53、SMAD2和转化生长因子-β（TGF-β）增加（p＜0.05）。QLSP和胃复春均可增加E-钙黏蛋白，减少N-钙黏蛋白、波形蛋白、p53、SMAD2和TGF-β（p＜0.05）。
我们的研究表明，具有多成分、多靶点特点的中药复方QLSP可有效调节关键的上皮-间质转化（EMT）标志物及其上游/下游调节因子。在动物实验中，QLSP成功逆转了CAG模型大鼠的EMT过程。这一发现为CAG治疗提供了新的治疗靶点，不过在临床转化方面仍存在一些挑战：首先，大鼠CAG模型在病理特征和疾病进展方面与人类CAG不同，物种特异性的生理和代谢差异可能会限制这些发现的外推。其次，网络药理学分析确定白细胞介素-6（IL-6）与TP53一样，是QLSP干预CAG的另一个关键靶点。因此，未来的研究应进一步阐明QLSP通过IL-6相关途径调节EMT的分子机制，并通过精心设计的临床试验验证其疗效，最终全面了解QLSP在CAG中的治疗潜力。
QLSP可能通过调节p53/TGF-β信号通路抑制胃黏膜上皮细胞的上皮-间质转化（EMT），从而预防CAG。
