Peng-Yu Chen1, Chong Yuan2, Zong-Chao Hong3, Ying Zhang4, Xin-Ge Ke5, Bing Yu6, Chen Wang7, Xue-Cheng Xiao8, He-Zhen Wu9, Yan-Fang Yang10. 1. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: 851086861@qq.com. 2. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: 1367147371@qq.com. 3. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: zchong369@163.com. 4. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: zying1105@163.com. 5. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: 2464663120@qq.com. 6. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: 20405710@qq.com. 7. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: 2359131998@qq.com. 8. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. Electronic address: xiaoxuecheng1968@163.com. 9. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, 430065, China; Collaborative Innovation Center of Traditional Chinese Medicine of New Products for Geriatrics Hubei Province, Wuhan, 430065, China. Electronic address: hezh_wu@163.com. 10. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, 430065, China; Collaborative Innovation Center of Traditional Chinese Medicine of New Products for Geriatrics Hubei Province, Wuhan, 430065, China. Electronic address: yyf0204@hbtcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: "Huai Hua San" (HHS) is one of the first hundred ancient classic prescriptions drugs, which is commonly used to treat hemorrhoids, colitis, and other symptoms of wind heat in stool. However, the potential molecular mechanism of action of this substance remains unclear. AIMS OF THE STUDY: In this study, we explored the active compounds of HHS for the treatment of ulcerative colitis (UC), predicted the potential targets of the drug, and studied its mechanism of action through network pharmacology via in vitro and in vivo experiments. MATERIALS AND METHODS: First, we identified the active compounds and key targets of HHS for treating UC via network pharmacology. The key signaling pathways associated with the anti-inflammatory effect of HHS were analyzed. The anti-inflammatory effects of HHS and its active compounds were studied using the RAW264.7 inflammatory cell model in vitro. Furthermore, we used the dextran sulfate sodium (DSS) mouse model to explore the efficacy and mechanism of HHS in UC in vivo, and the expression level of key proteins were detected by Western blotting. RESULTS: In all, 23 compounds and 97 targets were obtained from TCMSP database, PharmMapper database, and GeneCards database. After enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG), HIF-1 signaling pathway, PI3K/AKT signaling pathway, and VEGF signaling pathway were identified to be the top three signaling pathways associated with UC treatment. The results of molecular docking showed that the docking scores of the top 10 active compounds were higher than the threshold values. In vitro, different concentrations of HHS and the four main active compounds could effectively inhibit the release of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 β. In vivo, HHS could alleviate UC symptoms. CONCLUSION: Taken together, the treatment of UC with HHS may alleviate the inflammatory response of the colon, and HHS mainly inhibits the EGFR/PI3K/AKT/HIF-1/VEGF signaling pathways.
ETHNOPHARMACOLOGICAL RELEVANCE: "Huai Hua San" (HHS) is one of the first hundred ancient classic prescriptions drugs, which is commonly used to treat hemorrhoids, colitis, and other symptoms of wind heat in stool. However, the potential molecular mechanism of action of this substance remains unclear. AIMS OF THE STUDY: In this study, we explored the active compounds of HHS for the treatment of ulcerative colitis (UC), predicted the potential targets of the drug, and studied its mechanism of action through network pharmacology via in vitro and in vivo experiments. MATERIALS AND METHODS: First, we identified the active compounds and key targets of HHS for treating UC via network pharmacology. The key signaling pathways associated with the anti-inflammatory effect of HHS were analyzed. The anti-inflammatory effects of HHS and its active compounds were studied using the RAW264.7 inflammatory cell model in vitro. Furthermore, we used the dextran sulfate sodium (DSS) mouse model to explore the efficacy and mechanism of HHS in UC in vivo, and the expression level of key proteins were detected by Western blotting. RESULTS: In all, 23 compounds and 97 targets were obtained from TCMSP database, PharmMapper database, and GeneCards database. After enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG), HIF-1 signaling pathway, PI3K/AKT signaling pathway, and VEGF signaling pathway were identified to be the top three signaling pathways associated with UC treatment. The results of molecular docking showed that the docking scores of the top 10 active compounds were higher than the threshold values. In vitro, different concentrations of HHS and the four main active compounds could effectively inhibit the release of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1 β. In vivo, HHS could alleviate UC symptoms. CONCLUSION: Taken together, the treatment of UC with HHS may alleviate the inflammatory response of the colon, and HHS mainly inhibits the EGFR/PI3K/AKT/HIF-1/VEGF signaling pathways.
Authors: Bei Shi; Suxian Liu; Aoshuang Huang; Mengyun Zhou; Boyun Sun; Hui Cao; Jingyi Shan; Bo Sun; Jiang Lin Journal: Evid Based Complement Alternat Med Date: 2021-11-02 Impact factor: 2.629