Mechanism of Shaoyao Decoction in treatment of ulcerative colitis based on network pharmacology and molecular docking technology

LU Ai-ni1 WANG De-long1 ZHAO Fang1 CHEN Rui-jie1 CHEN Wei-qiao1 ZHENG Hong-bin1 JI Xu-ming1

(1.School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China 310053)

【Abstract】 Objective Network pharmacology and molecular docking technology were used to study the material basis and possible mechanism of Shaoyao Decoction in the treatment of ulcerative colitis (UC). Methods TCMSP and TCMID were used to obtain the potential active components and targets of Shaoyao Decoction. GeneCard and OMIM were used to search disease targets. The common targets obtained by matching drug targets with disease targets were imported into String to construct a PPI network, and Cyto NCA plug-in was used to screen key targets. The network diagram was plotted by connecting the key targets with the corresponding components, so as to screen the key components. GO and KEGG enrichment analyses were performed on key targets. SYBYL-X2.0 software was used to dock the molecules of the key components with the key targets. The rat UC model was replicated in vivo. After the intervention with Shaoyao Decoction, the disease activity index (DAI) was observed; the colonic pathological damage was evaluated; the levels of TNF-α, IL-4, and CXCR4 were detected by ELISA. Results A total of 424 potential active components were found in Shaoyao Decoction. The key components included quercetin, palmitic acid, catechin, and procyanidins, etc. Its 41 key targets for UC were mainly related to the positive regulation of transcription, the negative regulation of apoptosis process, signal transduction, and other biological processes. The key targets played a role in treating UC through signaling pathways such as TNF, HIF-1, cancer pathway, TLR, PI3 K-Akt, et al. Molecular docking results showed that key components had good binding activities with corresponding targets. Shaoyao Decoction improved colonic pathological damage, down-regulated the levels of TNF-α and CXCR4, and up-regulated the level of IL-4 in vivo. Conclusion Shaoyao Decoction exerts the therapeutic effects against UC via “multiple components, multiple targets, and multiple pathways”, which has laid a foundation for further study of its mechanism.

【Keywords】 Shaoyao Decoction; ulcerative colitis; network pharmacology; molecular docking; in vivo experiment; quercetin; palmitic acid; catechin; procyanidins;


【Funds】 National Natural Science Foundation of China (81573871) Zhejiang Provincial Science and Technology Project of Traditional Chinese Medicine (2020ZB061)

Download this article

(Translated by SUI T)


    [1] Danese S, Fiocchi C. Ulcerative colitis [J]. N Engl J Med, 2011, 365 (18): 1713–25.

    [2] De Lange K M, Moutsianas L, Lee J C, et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease [J]. Nat Genet, 2017, 49 (2): 256–261.

    [3] Piovani D, Danese S, Peyrin-Biroulet L, et al. Environmental risk factors for inflammatory bowel diseases: An umbrella review of meta-analyses [J]. Gastroenterology, 2019, 157 (3): 647–659.

    [4] Franzosa E A, Sirota-Madi A, Avila-Pacheco J, et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease [J]. Nat Microbiol, 2019, 4 (2): 293–305.

    [5] Neurath M F. Cytokines in inflammatory bowel disease [J]. Nat Rev Immunol, 2014, 14 (5): 329–342.

    [6] Mak W Y, Zhao M, Ng S C, et al. The epidemiology of inflammatory bowel disease: East meets West [J]. JGastroen Hepatol, 2019, 35 (3): 380–389.

    [7] Lv L T, Wang L J. Research Progress in Health Economic Evaluation of Intervention in Ulcerative Colitis in China [J]. China Journal of Pharmaceutical Economics, 2019, 14 (1): 113–120 (in Chinese).

    [8] Beaugerie L, Kirchgesner J. Balancing benefit vs risk of immunosuppressive therapy for individual patients with inflammatory bowel diseases [J]. Clin Gastroenterol Hepatol, 2019, 17 (3): 370–379.

    [9] Liu Q H, Huang W B, Luo Y F, et al. 溃疡性结肠炎当重湿热 [J]. Journal of Shaanxi University of Chinese Medicine, 2018, 41 (6): 13–16 (in Chinese).

    [10] Zhang Y, Li T Q. 李廷荃教授从“湿热”论治溃疡性结肠炎经验总结 [J]. World Latest Medicine Information, 2019, 19 (26): 208 (in Chinese).

    [11] Song N G. 刘完素医学全书 [M]. Beijing: China Press of Traditional Chinese Medicine Co., Ltd., 2006 (in Chinese).

    [12] Li R. 芍药汤加味保留灌肠治疗慢性溃疡性结肠炎的疗效及预后的影响分析 [J]. Journal of Sichuan of Traditional Chinese Medicine, 2019, 37 (9): 95–98 (in Chinese).

    [13] Ding H H. 芍药汤变方配合美沙拉嗪治疗溃疡性结肠炎湿热内蕴型的疗效分析 [J]. Chinese Journal of Traditional Medical Science and Technology, 2019, 26 (5): 744–745 (in Chinese).

    [14] Shi X Q, Yue S J, Tang Y P, et al. A network pharmacology approach to investigate the blood enriching mechanism of Danggui Buxue Decoction [J]. J Ethnopharmacol, 2019, 235: 227–242.

    [15] Jia X Y, Li S, Zhang H, et al. 5% TNBS coordinate with different doses of ethanol to optimize the model of UC in rats [J]. Shaanxi Journal of Traditional Chinese Medicine, 2016, 37 (7): 926–928 (in Chinese).

    [16] Huang J H, Huang X H, Chen Z Y, et al. Dose conversion among different animals and healthy volunteers in pharmacological study [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9 (9): 1069–1072 (in Chinese).

    [17] Murthy S N, Cooper H S, Shim H, et al. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin [J]. Dig Dis Sci, 1993, 38 (9): 1722–1734.

    [18] Deng G Z, Lin J X, Wu C W, et al. Molecular docking in Naomaitong Formula preparations multi-target effect on ischemic stroke [J]. Chinese Traditional Patent Medicine, 2016, 38 (8): 1673–1678 (in Chinese).

    [19] Fan Q M, Yang Y T, Xiao M F, et al. Interaction between components of Buyang Huanwu Decoction and targets associated with ischemic stroke based on molecular docking method [J]. Chinese Traditional and Herbal Drugs, 2019, 50 (17): 4200–4208 (in Chinese).

    [20] van Gennep S, KontéK, Meijer B, et al. Systematic review with meta-analysis: Risk factors for thiopurine-induced leukopenia in IBD [J]. Aliment Pharm Ther, 2019, 50 (5): 484–506.

    [21] Neurath M F. Current and emerging therapeutic targets for IBD [J]. Nat Rev Gastro Hepat, 2017, 14 (5): 269–78.

    [22] Pazmandi J, Kalinichenko A, Ardy R C, et al. Early-onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms [J]. Immunol Rev, 2019 2, 87 (1): 162–185.

    [23] Zhang Z, Shen P, Xie W, et al. Pingwei San ameliorates dextran sulfate sodium-induced chronic colitis in mice [J]. J Ethnopharmacol, 2019, 236: 91–99.

    [24] Chen M, Tang T C, Wang Y, et al. Randomised clinical trial: Tong-Xie-Yao-Fang granules versus placebo for patients with diarrhoea-predominant irritable bowel syndrome [J]. Aliment Pharm Ther, 2018, 48 (2): 160–168.

    [25] Gong S S, Fan Y H, Wang S Y, et al. Mucosa repair mechanisms of Tong-Xie-Yao-Fang mediated by CRH-R2in murine, dextran sulfate sodium-induced colitis [J]. World J Gastroentero, 2018, 24 (16): 1766–1778.

    [26] Jeon Y J, Lee J S, Cho Y R, et al. Banha-sasim-tang improves gastrointestinal function in loperamide-induced functional dyspepsia mouse model [J]. J Ethnopharmacol, 2019, 238: 111834.

    [27] Wa H F, Qi C J. 芍药汤加减联合常规西药治疗溃疡性结肠炎患者的临床效果 [J]. Chinese Journal of Coloproctology, 2019, 39 (5): 77 (in Chinese).

    [28] Chen J L, Chen J F, Han Y B, et al. 芍药汤保留灌肠对湿热型溃疡性结肠炎患者炎性因子的影响 [J]. Chinese Journal of Integrated Traditional and Western Medicine on Digestion, 2018, 26 (11): 938–940 (in Chinese).

    [28] Chen J L, Chen J F, Han Y B, et al. 芍药汤保留灌肠对湿热型溃疡性结肠炎患者炎性因子的影响 [J]. Chinese Journal of Integrated Traditional and Western Medicine on Digestion, 2018, 26 (11): 938–940 (in Chinese).

    [30] Hopkins A L. Network pharmacology [J]. Nat Biotechnol, 2007, 25 (10): 1110–1111.

    [31] Li S. Network target: a starting point for traditional Chinese medicine network pharmacology [J]. China Journal of Chinese Materia Medica, 2011, 36 (15): 2017–2020 (in Chinese).

    [32] Sotnikova R, Nosalova V, Navarova J. Efficacy of quercetin derivatives in prevention of ulcerative colitis in rats [J]. Interdiscip Toxicol, 2013, 6 (1): 9–12.

    [33] Dong L H. 叉分蓼抗溃疡性结肠炎的物质基础与作用机制研究 [D]. Nanchang: Jiangxi University of Traditional Chinese Medicine, 2019 (in Chinese).

    [34] Wang Y H, Ge B, Yang S H, et al. Effects of proanthocyanidins from grape seeds on levels of cytokines in colon tissues of rats with recurrent colitis [J]. Chinese Journal of Hospital Pharmacy, 2015, 35 (16): 1453–1456 (in Chinese).

    [35] Wang Y H. 葡萄籽原花青素治疗大鼠复发性溃疡性结肠炎的作用及其机理研究 [D]. Lanzhou: Lanzhou University, 2010 (in Chinese).

    [36] Bendjelloul F, Rossmann P, MalýP, et al. Detection of ICAM-1 in experimentally induced colitis of ICAM-1-deficient and wild-type mice: an immunohistochemical study [J]. Histochem J, 2000, 32 (12): 703–9.

    [37] Xu Y Q, Li H L, Qiu J Q, et al. Effects of the Tongxie Ercao decoction on the expression of related genes of ulcerative colitis rats of liver-depression and spleen-deifciency type [J]. Clinical Journal of Chinese Medicine, 2016, 8 (8): 3–7 (in Chinese).

    [38] Yang Q, Qian D P, Yang X Y, et al. FEffect of Tripteryginum wilfordii polyglycoside on Fas / FasL and p38 MAPK signaling pathway expression in ulcerative colitis rats [J]. Chinese Pharmacological Bulletin, 2019, 35 (2): 218–223 (in Chinese).

    [39] He Y H, Li Y L, Xiang Y Y, et al. The role of SDF-1/CXCR4 and downstream signaling pathways in the course of OA [J]. The Journal of Practical Medicine, 2019, 35 (22): 3563–3567 (in Chinese).

    [40] Perkins N D. Integrating cell-signalling pathways with NF-κB and IKK function [J]. Nat Rev Mol Cell Biol, 2007, 8 (1): 49–62.

    [41] Wu X F, Xu R, Ouyang Z J, et al. Beauvericin ameliorates experimental colitis by inhibiting activated Tcells via downregulation of the PI3K/Akt signaling pathway [J]. Plo S One, 2013, 8 (12): e83013.

    [42] Kim H, Banerjee N, Barnes R C, et al. Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the mi R-126/PI3K/AKT/m TORaxis in vitro and in vivo [J]. Mol Carcinogen, 2017, 56 (1): 197–207.

    [43] Chen Q, Duan X, Fan H, et al. Oxymatrine protects against DSS-induced colitis via inhibiting the PI3K/AKTsignaling pathway [J]. Int Immunopharmacol, 2017, 53: 149–157.

    [44] Coskun M, Salem M, Pedersen J, et al. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease [J]. Pharmacol Res, 2013, 76: 1–8.

This Article


CN: 12-1108/R

Vol 51, No. 23, Pages 6035-6044

December 2020


Article Outline



  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • References