Cui Y, Wang D, Xie D, Wang H, Xu R, Tang X, Zhang Y
Department of Traditional Chinese Medicine of the Sixth Clinical Center, Chinese PLA General Hospital, Beijing 100853, China.
Second Outpatient Department, Aerospace Center Hospital, Beijing 100049, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Feb 20;44(2):217-225. doi: 10.12122/j.issn.1673-4254.2024.02.03.
To investigate the efficacy of Gel (SSWYG) for treating chronic diarrhea and explore its therapeutic mechanism.
Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules (control group, =40) or naval application with SSWYG (treatment group, =40) for one week, after which symptoms of chronic diarrhea were evaluated. The Chinese medicine system pharmacology analysis platform (TCMSP), GeneCards, NCBI, OMIM database and GEO database (GSE14841) were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets. The key targets were obtained by topological analysis for Gene Ontology (GO) and KEGG analyses. The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.
In both groups, gastrointestinal symptom rating scale (GSRS), Bristol Scale and TCM syndrome scores significantly improved after the treatments ( < 0.05), and better effects were observed in the treatment group ( < 0.05). Sixtyeight targets of SSWYG in treating chronic diarrhea were obtained, and 33 most probable ones were screened out by topological analysis. GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways. Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3, JNK, IL1B, IL6, and AKT1. JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.
SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways CASP3 and JUN, suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.
探讨四神丸加味（SSWYG）治疗慢性腹泻的疗效并探究其治疗机制。
将80例脾胃虚弱型慢性腹泻患者随机分为两组，一组进行生活方式调整并使用双歧三联活菌胶囊干预（对照组，n = 40），另一组采用SSWYG脐部给药（治疗组，n = 40），干预一周后评估慢性腹泻症状。利用中药系统药理学分析平台（TCMSP）、GeneCards、NCBI、OMIM数据库和GEO数据库（GSE14841）获取SSWYG的活性成分和靶蛋白以及慢性腹泻相关靶点。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析的拓扑分析获得关键靶点。使用AutoDock软件通过分子对接验证SSWYG对特定靶点的亲和力和结合特性。
两组治疗后胃肠道症状评定量表（GSRS）、布里斯托量表和中医证候评分均显著改善（P < 0.05），且治疗组效果更佳（P < 0.05）。获得了SSWYG治疗慢性腹泻的68个靶点，通过拓扑分析筛选出33个最可能的靶点。GO和KEGG分析确定了几条与慢性腹泻相关的通路，包括肿瘤坏死因子（TNF）和白细胞介素-17（IL-17）通路。分子对接研究表明，SSWYG的核心成分与关键靶点半胱天冬酶3（CASP3）、应激活化蛋白激酶（JNK）、白细胞介素1β（IL1B）、白细胞介素6（IL6）和蛋白激酶B（AKT1）具有良好的亲和力。JUN和CASP3与SSWYG的多种主要活性成分结合能最低且结合稳定性最高。
SSWYG可能通过调节TNF和IL-17以及其他通路（如CASP3和JUN）显著改善慢性腹泻的临床症状，提示SSWYG的治疗机制复杂，涉及多种成分和靶点以及多条通路的协同调节。
