Zeng Xing-Lin, Zhu Lian-Jun, Zhang Yu, Yang Xiang-Dong, Zhu Yu-Jun
Clinical Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China.
Department of General Surgery, Jiangbei Campus of The First Affiliated Hospital of Army Medical University, Chongqing 400020, China.
World J Gastroenterol. 2025 Aug 14;31(30):109187. doi: 10.3748/wjg.v31.i30.109187.
Xuanshen decoction (XSD) is a traditional Chinese medicine formulation that is often applied in treating slow transit constipation (STC). However, its specific therapeutic mechanism remains to be characterized.
To investigate the mechanism of XSD for STC, we combined network pharmacology prediction, molecular docking analysis, and studies.
The therapeutic effects of XSD on loperamide-induced STC in rats were assessed through 24-hour fecal number, fecal moisture content, and intestinal propelling rate. Hematoxylin-eosin and Alcian blue/periodic acid-Schiff staining were applied to analyze colonic mucosa for histopathological presentation and mucin production. Next, the mechanism of action of XSD for STC was elucidated through network pharmacology and molecular docking analyses, and the findings were validated by the animal experiments.
XSD significantly alleviated the symptoms of STC in rats. Relative to the STC rats, in the medium-dose XSD and high-dose XSD rats, stem cell factor, C-kit, phospho-phosphoinositide 3-kinase/phosphoinositide 3-kinase, phospho-protein kinase B/protein kinase B, catalase, and superoxide dismutase were substantially upregulated ( < 0.01); nuclear factor erythroid 2-related factor 2 (nuclear/cytoplasmic) and B-cell lymphoma 2 (Bcl-2) were increased ( < 0.05), while cleaved caspase-3, Bcl-2-associated X protein (Bax)/Bcl-2, and malondialdehyde were significantly reduced ( < 0.01). Heme oxygenase-1 and glutathione peroxidase in the high-dose XSD group were significantly increased ( < 0.01), and Bax was statistically lowered ( < 0.01); glutathione peroxidase in the medium-dose XSD group was increased ( < 0.05), while Bax was reduced ( < 0.05).
XSD may inhibit oxidative-stress-induced apoptosis in interstitial cells of Cajal by stimulating the phosphoinositide 3-kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 pathway, thereby effectively treating STC.
玄参汤（XSD）是一种常用于治疗慢传输型便秘（STC）的中药制剂。然而，其具体治疗机制仍有待明确。
为探究玄参汤治疗STC的机制，我们结合了网络药理学预测、分子对接分析和实验研究。
通过24小时粪便数量、粪便含水量和肠道推进率评估玄参汤对洛哌丁胺诱导的大鼠STC的治疗效果。应用苏木精-伊红染色和阿尔辛蓝/过碘酸-希夫染色分析结肠黏膜的组织病理学表现和黏蛋白产生情况。接下来，通过网络药理学和分子对接分析阐明玄参汤治疗STC的作用机制，并通过动物实验验证研究结果。
玄参汤显著减轻了大鼠STC的症状。与STC大鼠相比，中剂量玄参汤组和高剂量玄参汤组大鼠的干细胞因子、C-kit、磷酸化磷脂酰肌醇3激酶/磷脂酰肌醇3激酶、磷酸化蛋白激酶B/蛋白激酶B、过氧化氢酶和超氧化物歧化酶显著上调（P<0.01）；核因子红细胞2相关因子2（核/质）和B细胞淋巴瘤2（Bcl-2）增加（P<0.05），而裂解的半胱天冬酶-3、Bcl-2相关X蛋白（Bax）/Bcl-2和丙二醛显著降低（P<0.01）。高剂量玄参汤组血红素加氧酶-1和谷胱甘肽过氧化物酶显著增加（P<0.01），Bax统计学降低（P<0.01）；中剂量玄参汤组谷胱甘肽过氧化物酶增加（P<0.05），而Bax降低（P<0.05）。
玄参汤可能通过刺激磷脂酰肌醇3激酶/蛋白激酶B/核因子红细胞2相关因子2通路抑制氧化应激诱导的 Cajal 间质细胞凋亡，从而有效治疗 STC。
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