Background:Traditional Chinese medicine (TCM) Xiaojianzhong Tang (XJZ) has a favorable efficacy in the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism has not been fully explained.Objective:The purpose of this study was to find the potential mechanism of XJZ in the treatment of CAG using pharmacocoinformatics approaches.Methods:Network pharmacology was used to screen out the key compounds and key targets, MODELLER and GNNRefine were used to repair and refine proteins, Autodock vina was employed to perform molecular docking, Δ Lin_F9XGB was used to score the docking results, and Gromacs was used to perform molecular dynamics simulations (MD).Results:Kaempferol, licochalcone A, and naringenin, were obtained as key compounds, while AKT1, MAPK1, MAPK14, RELA, STAT1, and STAT3 were acquired as key targets. Among docking results, 12 complexes scored greater than five. They were run for 50ns MD. The free binding energy of AKT1-licochalcone A and MAPK1-licochalcone A was less than -15 kcal/mol and AKT1-naringenin and STAT3-licochalcone A was less than -9 kcal/mol. These complexes were crucial in XJZ treating CAG.Conclusion:Our findings suggest that licochalcone A could act on AKT1, MAPK1, and STAT3, and naringenin could act on AKT1 to play the potential therapeutic effect on CAG. The work also provides a powerful approach to interpreting the complex mechanism of TCM through the amalgamation of network pharmacology, deep learning-based protein refinement, molecular docking, machine learning-based binding affinity estimation, MD simulations, and MM-PBSA-based estimation of binding free energy.

2024-01-01·Journal of Ethnopharmacology

Mechanism of Xiaojianzhong decoction in alleviating aspirin-induced gastric mucosal injury revealed by transcriptomics and metabolomics

Article

作者: Zhou, Xiao-Yan ; Chen, Juan ; Zhang, Jia-Xiang ; Wei, Hai-Liang ; Bao, Sheng-Chuan ; Yan, Shu-Guang ; Li, Jing-Tao ; Chen, Ting ; Hu, Xin ; Liang, Yan

ETHNOPHARMACOLOGICAL RELEVANCEAspirin, as a first-line drug for the treatment of cardiovascular diseases, currently has high clinical usage. However, reports of aspirin-induced gastric mucosal injury are increasing. Xiaojianzhong decoction (XJZD), a classic traditional Chinese medicine formula, has been shown to alleviate gastric mucosal injury, although its potential mechanism of action requires further study.AIM OF THE STUDYThis study aimed to explore the effect and mechanism of XJZD in preventing aspirin-induced gastric mucosal injury.MATERIALS AND METHODSAspirin was used to induce damage in the morning, while XJZD was applied as an intervention in the afternoon. The compounds in the XJZD were analyzed by means of both high-performance liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry. The overall condition of the aspirin-related gastric mucosal injury was evaluated. The expressions of inflammatory factors and tight-junction-related proteins and apoptosis were observed via immunohistochemistry and immunofluorescence. The expression levels of the apoptosis-related proteins were detected using Western blot. Transcriptomics was used to perform the integrative analysis of gastric tissues, which was then validated. Molecular dynamics was used to explore the interaction of key compounds within the XJZD with relevant targets. Finally, non-targeted metabolomics was used to observe any metabolic changes and construct a network between the differentially expressed genes and the differential metabolites to elucidate their potential relationship.RESULTSXJZD can alleviate inflammation response, maintain the gastric mucosal barrier's integrity, reduce apoptosis and necroptosis levels, and promote the proliferation and repair of gastric mucosal tissues. Its mechanism of action may be related to the regulation of TNF-α signaling. Furthermore, molecular docking showed that the cinnamaldehyde within XJZD played an important role in its effects. In addition, XJZD can correct metabolic disorders, mainly regulating amino acid metabolism pathways. Moreover, six differential genes (Cyp1a2, Cyp1a1, Pla2g4c, etc.) were determined to alleviate both gastric mucosal injury and inflammation by regulating arachidonic acid metabolism, Tryptophan metabolism, etc. CONCLUSIONS: This study is the first to report that XJZD can inhibit necroptosis and gastric mucosal injury induced by aspirin, thereby revealing the complex mechanism of XJZD in relation to alleviating gastric mucosal injury from multiple levels and perspectives.

2023-12-31·Pharmaceutical Biology

Xiaojianzhong decoction attenuates aspirin-induced gastric mucosal injury via the PI3K/AKT/mTOR/ULK1 and AMPK/ULK1 pathways

Article

作者: Li, Jingtao ; Wei, Hailiang ; Zhang, Jiaxiang ; Liang, Yan ; Chen, Juan ; Hu, Xin ; Chen, Ting ; Yan, Shuguang ; Bao, Shengchuan

CONTEXTXiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear.OBJECTIVETo investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms.MATERIALS AND METHODSC57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed.RESULTSThe results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa.DISCUSSION AND CONCLUSIONSXJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

100 项与小建中汤相关的药物交易

登录后查看更多信息

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
肠炎	日本	Ohsugi Pharmaceutical Co., Ltd.	1986-08-22
遗尿症	日本	Ohsugi Pharmaceutical Co., Ltd.	1986-08-22
疲劳	日本	Ohsugi Pharmaceutical Co., Ltd.	1986-08-22
入睡和睡眠障碍	日本	Ohsugi Pharmaceutical Co., Ltd.	1986-08-22