Exploration of potential mechanisms of Shuganning injection for non-alcoholic fatty liver disease through network pharmacology and molecular docking_West China Medical Journal

Authors：

 LU Cuncun ¹ , WANG Haibo ² , KE Lixin ³ ,  ZHANG Qiang ⁴

1. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China;
2. Department of Critical Care Medicine, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P. R. China;
3. Department of Pediatrics, Medical Center of University of Groningen, Groningen 9713GZ, Netherlands;
4. Department of Gastroenterology, the First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan 450000, P. R. China;

Corresponding author：

LU Cuncun, Email: lu17metrics@163.com; ZHANG Qiang, Email: zhangqiangq7@126.com

Keywords：

Network pharmacology; molecular docking; Shuganning injection; baicalin; action mechanism

DOI：

10.7507/1002-0179.202406206

Video：

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Objective To explore the potential mechanism of Shuganning injection for non-alcoholic fatty liver disease (NAFLD) through network pharmacology and molecular docking techniques. Methods Information on the active compounds of Shuganning injection and their target proteins, as well as disease-related targets of NAFLD, were collected from multiple public databases from May 23rd to 28th, 2024, for protein interaction network analysis and pathway enrichment analysis. A multi-level network of “herb-compound-target-disease” of Shuganning injection for NAFLD was constructed. Molecular docking was performed on the top 5 key active compounds ranked in the degree centrality of the “core target-active compound” network and the core action targets. Results Finally, 140 active compounds of Shuganning injection and 486 potential targets, 1058 NAFLD-related targets, 154 common targets for NAFLD and Shuganning injection were obtained. Topological analysis of the common target protein interaction network identified 16 key target proteins of protein kinase B1, peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1, interleukin-6, and matrix metalloproteinase-9, etc. The gene ontology enrichment analysis showed that their genes were involved in 179 biological processes, 13 cellular components, and 48 molecular functions. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that their genes were involved in 99 pathways of cancer, lipid and atherosclerosis, NAFLD and insulin resistance, etc. The constructed multi-level network of “herb-compound-target-disease” consisted of 102 nodes and 208 edges. The molecular docking results showed that the 5 key active compounds of baicalin, acacetin, sitosterol, β-sitosterol, and ganoderic acid A had high affinity for the core target proteins. Conclusion Shuganning injection may exert therapeutic effects on NAFLD through active compounds like baicalin, acacetin, sitosterol, β-sitosterol and ganoderic acid A, acting on key target proteins such as protein kinase B1, peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1, interleukin-6, and matrix metalloproteinase-9, regulating pathways related to lipids and atherosclerosis, NAFLD, and insulin resistance.

Citation： LU Cuncun, WANG Haibo, KE Lixin, ZHANG Qiang. Exploration of potential mechanisms of Shuganning injection for non-alcoholic fatty liver disease through network pharmacology and molecular docking. West China Medical Journal, 2024, 39(12): 1911-1916. doi: 10.7507/1002-0179.202406206 Copy

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2.	Lou TW, Yang RX, Fan JG. The global burden of fatty liver disease: the major impact of China. Hepatobiliary Surg Nutr, 2024, 13(1): 119-123.
3.	中华中医药学会肝胆病分会. 非酒精性脂肪性肝炎中医诊疗指南. 中西医结合肝病杂志, 2022, 32(11): 附Ⅲ-附Ⅵ.
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5.	舒肝宁注射液治疗急性和慢性肝病共识专家委员会. 舒肝宁注射液治疗急性和慢性肝病专家共识(2020 版). 中华实验和临床感染病杂志(电子版), 2020, 14(5): 353-360.
6.	Zhang P, Zhang D, Zhou W, et al. Network pharmacology: towards the artificial intelligence-based precision traditional Chinese medicine. Brief Bioinform, 2023, 25(1): bbad518.
7.	张立娜, 张向宇, 朱雨晴, 等. 基于网络药理学探讨舒肝宁注射液治疗乙型病毒性肝炎的作用机制. 现代药物与临床, 2024, 39(3): 595-603.
8.	马璐, 田国祥, 耿辉, 等. 中药系统药理数据库 TCMSP 及其分析应用简介. 中国循证心血管医学杂志, 2020, 12(12): 1413-1416.
9.	Zhang LX, Dong J, Wei H, et al. TCMSID: a simplified integrated database for drug discovery from traditional chinese medicine. J Cheminform, 2022, 14(1): 89.
10.	Szklarczyk D, Santos A, von Mering C, et al. STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res, 2016, 44(D1): D380-D384.
11.	Piñero J, Bravo À, Queralt-Rosinach N, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res, 2017, 45(D1): D833-D839.
12.	Otasek D, Morris JH, Bouças J, et al. Cytoscape automation: empowering workflow-based network analysis. Genome Biol, 2019, 20(1): 185.
13.	Liu Y, Yang X, Gan J, et al. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res, 2022, 50(W1): W159-W164.
14.	Kaya E, Yilmaz Y. Metabolic-associated fatty liver disease (MAFLD): a multi-systemic disease beyond the liver. J Clin Transl Hepatol, 2022, 10(2): 329-338.
15.	王箭焱. 舒肝宁注射液联合复方甘草酸苷对非酒精性脂肪性肝炎患者脂代谢、肝功能的影响. 中国医学创新, 2023, 20(22): 45-48.
16.	高文, 张晓慧, 张译之, 等. 舒肝宁注射液对非酒精性脂肪性肝病组织工程肝保护作用的机制研究. 中西医结合肝病杂志, 2022, 32(3): 248-251.
17.	陈元堃, 曾奥, 罗振辉, 等. β-谷甾醇药理作用研究进展. 广东药科大学学报, 2021, 37(1): 148-153.
18.	Zhang P, Liu N, Xue M, et al. β-Sitosterol reduces the content of triglyceride and cholesterol in a high-fat diet-induced non-alcoholic fatty liver disease zebrafish (danio rerio) model. Animals (Basel), 2024, 14(9): 1289.
19.	周海玥, 汤威, 姜婧, 等. β-谷甾醇与豆甾醇对非酒精性脂肪肝作用的体外研究. 营养学报, 2016, 38(5): 456-461.
20.	Liu F, Shi K, Dong J, et al. Ganoderic acid A attenuates high-fat-diet-induced liver injury in rats by regulating the lipid oxidation and liver inflammation. Arch Pharm Res, 2020, 43(7): 744-754.
21.	Zhu J, Ding J, Li S, et al. Ganoderic acid A ameliorates non-alcoholic streatohepatitis (NASH) induced by high-fat high-cholesterol diet in mice. Exp Ther Med, 2022, 23(4): 308.
22.	钱坤, 刘亚云, 张艳, 等. 中药抗非酒精性脂肪肝病分子机制的研究进展. 中草药, 2020, 51(19): 5083-5092.
23.	艾正琳, 洪珊, 胡居龙, 等. 黄芩苷治疗非酒精性脂肪性肝炎大鼠抗炎的疗效. 山东大学学报(医学版), 2019, 57(7): 55-60.
24.	马纳, 李亚静, 范吉平. 金合欢素药理研究进展. 中国现代应用药学, 2018, 35(10): 1591-1595.
25.	甘璐, 孙晓春, 彭国平, 等. 刺槐素激活 PPARγ/NF-κB 通路改善高糖/高脂应激所致血管内皮细胞功能失调的研究. 药品评价, 2023, 20(3): 294-298.
26.	阮雄中, 陈压西. 代谢性炎症与非酒精性脂肪性肝病的发生与发展. 中华消化杂志, 2020, 40(9): 581-584.
27.	Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell, 2021, 184(10): 2537-2564.
28.	陈聪, 周香辉, 张兵, 等. 基于网络药理学及计算机辅助药物设计研究护肝宁片治疗非酒精性脂肪性肝病的作用机制. 药学学报, 2023, 58(3): 695-710.
29.	王宁, 李京涛, 常占杰, 等. PI3K/AKt 信号通路在胰岛素抵抗所致非酒精性脂肪性肝病中作用机制的研究进展. 胃肠病学和肝病学杂志, 2019, 28(11): 1308-1311.
30.	冯帅霞, 徐莹, 韩涵. 过氧化物酶体增殖物激活受体(PPAR)在肝脏疾病中的作用及潜在意义. 临床肝胆病杂志, 2023, 39(7): 1747-1753.
31.	Kuang J, Wang J, Li Y, et al. Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis. Cell Metab, 2023, 35(10): 1752-1766.e8.
32.	Yang H, Arif M, Yuan M, et al. A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease. iScience, 2021, 24(11): 103222.
33.	芦建慧, 陈俭静, 彭相文, 等. 非酒精性脂肪肝患者血清白介素-6 的检测及意义. 中国现代医学杂志, 2013, 23(32): 45-49.
34.	Duan Y, Pan X, Luo J, et al. Association of inflammatory cytokines with non-alcoholic fatty liver disease. Front Immunol, 2022, 13: 880298.
35.	刘月白, 周义, 李昌平. 非酒精性脂肪性肝病中 MMP-9 作用的研究进展. 现代临床医学, 2019, 45(2): 81-83, 87.
36.	罗玲, 黄嘉璐, 杨子华, 等. 基于网络药理学和分子对接探讨大花红景天在 2 型糖尿病合并阿尔茨海默病中应用的潜在分子机制. 华西医学, 2023, 38(4): 567-573.

1. 中华医学会肝病学分会. 代谢相关(非酒精性)脂肪性肝病防治指南(2024 年版). 中华肝脏病杂志, 2024, 32(5): 418-434.
2. Lou TW, Yang RX, Fan JG. The global burden of fatty liver disease: the major impact of China. Hepatobiliary Surg Nutr, 2024, 13(1): 119-123.
3. 中华中医药学会肝胆病分会. 非酒精性脂肪性肝炎中医诊疗指南. 中西医结合肝病杂志, 2022, 32(11): 附Ⅲ-附Ⅵ.
4. Dai X, Feng J, Chen Y, et al. Traditional Chinese medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives. Chin Med, 2021, 16(1): 68.
5. 舒肝宁注射液治疗急性和慢性肝病共识专家委员会. 舒肝宁注射液治疗急性和慢性肝病专家共识(2020 版). 中华实验和临床感染病杂志(电子版), 2020, 14(5): 353-360.
6. Zhang P, Zhang D, Zhou W, et al. Network pharmacology: towards the artificial intelligence-based precision traditional Chinese medicine. Brief Bioinform, 2023, 25(1): bbad518.
7. 张立娜, 张向宇, 朱雨晴, 等. 基于网络药理学探讨舒肝宁注射液治疗乙型病毒性肝炎的作用机制. 现代药物与临床, 2024, 39(3): 595-603.
8. 马璐, 田国祥, 耿辉, 等. 中药系统药理数据库 TCMSP 及其分析应用简介. 中国循证心血管医学杂志, 2020, 12(12): 1413-1416.
9. Zhang LX, Dong J, Wei H, et al. TCMSID: a simplified integrated database for drug discovery from traditional chinese medicine. J Cheminform, 2022, 14(1): 89.
10. Szklarczyk D, Santos A, von Mering C, et al. STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res, 2016, 44(D1): D380-D384.
11. Piñero J, Bravo À, Queralt-Rosinach N, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res, 2017, 45(D1): D833-D839.
12. Otasek D, Morris JH, Bouças J, et al. Cytoscape automation: empowering workflow-based network analysis. Genome Biol, 2019, 20(1): 185.
13. Liu Y, Yang X, Gan J, et al. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res, 2022, 50(W1): W159-W164.
14. Kaya E, Yilmaz Y. Metabolic-associated fatty liver disease (MAFLD): a multi-systemic disease beyond the liver. J Clin Transl Hepatol, 2022, 10(2): 329-338.
15. 王箭焱. 舒肝宁注射液联合复方甘草酸苷对非酒精性脂肪性肝炎患者脂代谢、肝功能的影响. 中国医学创新, 2023, 20(22): 45-48.
16. 高文, 张晓慧, 张译之, 等. 舒肝宁注射液对非酒精性脂肪性肝病组织工程肝保护作用的机制研究. 中西医结合肝病杂志, 2022, 32(3): 248-251.
17. 陈元堃, 曾奥, 罗振辉, 等. β-谷甾醇药理作用研究进展. 广东药科大学学报, 2021, 37(1): 148-153.
18. Zhang P, Liu N, Xue M, et al. β-Sitosterol reduces the content of triglyceride and cholesterol in a high-fat diet-induced non-alcoholic fatty liver disease zebrafish (danio rerio) model. Animals (Basel), 2024, 14(9): 1289.
19. 周海玥, 汤威, 姜婧, 等. β-谷甾醇与豆甾醇对非酒精性脂肪肝作用的体外研究. 营养学报, 2016, 38(5): 456-461.
20. Liu F, Shi K, Dong J, et al. Ganoderic acid A attenuates high-fat-diet-induced liver injury in rats by regulating the lipid oxidation and liver inflammation. Arch Pharm Res, 2020, 43(7): 744-754.
21. Zhu J, Ding J, Li S, et al. Ganoderic acid A ameliorates non-alcoholic streatohepatitis (NASH) induced by high-fat high-cholesterol diet in mice. Exp Ther Med, 2022, 23(4): 308.
22. 钱坤, 刘亚云, 张艳, 等. 中药抗非酒精性脂肪肝病分子机制的研究进展. 中草药, 2020, 51(19): 5083-5092.
23. 艾正琳, 洪珊, 胡居龙, 等. 黄芩苷治疗非酒精性脂肪性肝炎大鼠抗炎的疗效. 山东大学学报(医学版), 2019, 57(7): 55-60.
24. 马纳, 李亚静, 范吉平. 金合欢素药理研究进展. 中国现代应用药学, 2018, 35(10): 1591-1595.
25. 甘璐, 孙晓春, 彭国平, 等. 刺槐素激活 PPARγ/NF-κB 通路改善高糖/高脂应激所致血管内皮细胞功能失调的研究. 药品评价, 2023, 20(3): 294-298.
26. 阮雄中, 陈压西. 代谢性炎症与非酒精性脂肪性肝病的发生与发展. 中华消化杂志, 2020, 40(9): 581-584.
27. Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell, 2021, 184(10): 2537-2564.
28. 陈聪, 周香辉, 张兵, 等. 基于网络药理学及计算机辅助药物设计研究护肝宁片治疗非酒精性脂肪性肝病的作用机制. 药学学报, 2023, 58(3): 695-710.
29. 王宁, 李京涛, 常占杰, 等. PI3K/AKt 信号通路在胰岛素抵抗所致非酒精性脂肪性肝病中作用机制的研究进展. 胃肠病学和肝病学杂志, 2019, 28(11): 1308-1311.
30. 冯帅霞, 徐莹, 韩涵. 过氧化物酶体增殖物激活受体(PPAR)在肝脏疾病中的作用及潜在意义. 临床肝胆病杂志, 2023, 39(7): 1747-1753.
31. Kuang J, Wang J, Li Y, et al. Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis. Cell Metab, 2023, 35(10): 1752-1766.e8.
32. Yang H, Arif M, Yuan M, et al. A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease. iScience, 2021, 24(11): 103222.
33. 芦建慧, 陈俭静, 彭相文, 等. 非酒精性脂肪肝患者血清白介素-6 的检测及意义. 中国现代医学杂志, 2013, 23(32): 45-49.
34. Duan Y, Pan X, Luo J, et al. Association of inflammatory cytokines with non-alcoholic fatty liver disease. Front Immunol, 2022, 13: 880298.
35. 刘月白, 周义, 李昌平. 非酒精性脂肪性肝病中 MMP-9 作用的研究进展. 现代临床医学, 2019, 45(2): 81-83, 87.
36. 罗玲, 黄嘉璐, 杨子华, 等. 基于网络药理学和分子对接探讨大花红景天在 2 型糖尿病合并阿尔茨海默病中应用的潜在分子机制. 华西医学, 2023, 38(4): 567-573.

West China Medical Journal

Exploration of potential mechanisms of Shuganning injection for non-alcoholic fatty liver disease through network pharmacology and molecular docking

Abstract Full text Figures/Tables Video References Cited by

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