文献类型：期刊文献

英文题名：Network pharmacology and experimental verification reveal the mechanism of Hedysari Radix and Curcumae Rhizoma with the optimal compatibility ratio against colitis-associated colorectal cancer

作者：Zhang, Yugui[1,2];Wang, Yanjun[1,2];Xin, Erdan[1,2];Zhang, Zhuanhong[1,2];Ma, Dingcai[1,2];Liu, Ting[1,2];Gao, Feiyun[1,2];Bian, Tiantian[1,2];Sun, Yujing[1,2,4];Wang, Maomao[1,2];Wang, Zhe[1,2];Yan, Xingke[3,5];Li, Yuefeng[1,2,4,5]

第一作者：张永刚

通信作者：Yan, XK[1];Yan, XK[2];Li, YF[2]

机构：[1]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Engn Res Ctr Chinese Med Pharmaceut Proc Gansu, Key Lab Stand & Qual Chinese Med Res Gansu, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Sci Res & Expt Ctr, Lanzhou 730000, Peoples R China;[5]35 Dingxi East Rd, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Acupuncture Moxibust & Tuina, Lanzhou 730000, Peoples R China;[2]corresponding author), 35 Dingxi East Rd, Lanzhou, Gansu, Peoples R China.|[10735db5df93766a96e5b]甘肃中医药大学针灸推拿学院;[10735]甘肃中医药大学;

年份：2024

卷号：322

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-85180584797);WOS:【SCI-EXPANDED(收录号:WOS:001143781400001)】；

基金：The authors acknowledge funding from the following funds: the National Natural Science Foundation of China (No. 81960713 and 82160750) , Gansu Provincial Education Department Industrial Support Plan Project (2021CYZC-21) and Gansu Provincial Department of Sci-ence and Technology-Science and Technology Plan (Innovation Base and Talent Plan) Basic Research Innovation Group Project (21JR7RA569) . The authors also thank the language polishing services from Home for Researchers editorial team (http:// www.home-for-resear

语种：英文

外文关键词：Hedysari Radix-Curcumae Rhizoma (vinegar processed); The optimal compatibility ratio; Mechanism; Intestinal permeability; PI3K/AKT signaling pathway

摘要：Ethnopharmacological relevance: The herb pair Astragali Radix (AR) and Curcumae Rhizoma (vinegar-processed, VPCR), derived from the traditional Chinese medicine (TCM) text 'Yixuezhongzhongcanxilu', have long been used to treat gastrointestinal diseases, notably colitis-associated colorectal cancer (CAC). Hedysari Radix (HR), belonging to the same Leguminosae family as AR but from a different genus, is traditionally used as a substitute for AR when paired with VPCR in the treatment of CAC. However, the optimal compatibility ratio for HR-VPCR against CAC and the underlying mechanisms remain unclear.Aim of the study: To investigate the optimal compatibility ratio and underlying mechanisms of HR-VPCR against CAC using a combination of comparative pharmacodynamics, network pharmacology, and experimental verification. Materials and methods: The efficacy of different compatibility ratios of HR-VPCR against CAC was evaluated using various indicators, including the body weight, colon length, tumor count, survival rate, disease activity index (DAI) score, Haemotoxylin and Eosin (H&E) pathological sections, inflammation cytokines (IL-1 beta, IL-6, IL-10, TNF-alpha), tumor markers (K-Ras, p53), and intestinal permeability proteins (claudin-1, E-cadherin, mucin-2). Then, the optimal compatibility ratio of HR-VPCR against CAC was determined based on the fuzzy matter-element analysis by integrating the above indicators. After high-performance liquid chromatography (HPLC) analysis for the optimal compatibility ratio of HR-VPCR, potential active components of HR-VPCR were identified by TCMSP and the previous bibliographies. Swiss Targets and GeneCards were adopted to predict the targets of the active components and the targets of CAC, respectively. Then, the common targets of HR-VPCR against CAC were obtained by Venn analysis. PPI networks were constructed in STRING. GO and KEGG enrichments were visualized by the David database. Finally, the predicted pathway was experimentally validated via Western blot.Results: Various compatibility ratios of HR-VPCR demonstrated notable therapeutic effects to some extent, evidenced by improvements in body weight, colon length, tumor count, pathological symptoms (DAI score), colon and organ indexes, survival rate, and modulation of inflammation factors (IL-1 beta, IL-6, IL-10, TNF-alpha), as well as tumor markers (K-Ras, p53), and down-regulation of intestinal permeability proteins (claudin-1, E-cadherin, mucin-2) in CAC mice. Among these ratios, the ratio 4:1 represents the optimal compatibility ratio by the fuzzy matter-element analysis. Thirty active components of HR-VPCR were carefully selected, targeting 553 specific genes. Simultaneously, 2022 targets associated with CAC were identified. 88 common targets were identified after generating a Venn plot. Following PPI network analysis, 29 core targets were established, with AKT1 ranking highest among them. Further analysis via GO and KEGG enrichment identified the PI3K-AKT signaling pathway as a potential mechanism. Experimental validation confirmed that HR-VPCR intervention effectively reversed the activated PI3K-AKT signaling pathway.Conclusions: The optimal compatibility ratio for the HR-VPCR herb pair in alleviating CAC is 4:1. HR-VPCR exerts its effects by alleviating intestinal inflammation, improving intestinal permeability, and regulating the PI3K-AKT signaling pathway.