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.	中華中醫藥學會肝膽病分會. 非酒精性脂肪性肝炎中醫診療指南. 中西醫結合肝病雜志, 2022, 32(11): 附Ⅲ-附Ⅵ.
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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.	張立娜, 張向宇, 朱雨晴, 等. 基于網絡藥理學探討舒肝寧注射液治療乙型病毒性肝炎的作用機制. 現代藥物與臨床, 2024, 39(3): 595-603.
8.	馬璐, 田國祥, 耿輝, 等. 中藥系統藥理數據庫 TCMSP 及其分析應用簡介. 中國循證心血管醫學雜志, 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.	Pi?ero 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, Bou?as 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. 舒肝寧注射液聯合復方甘草酸苷對非酒精性脂肪性肝炎患者脂代謝、肝功能的影響. 中國醫學創新, 2023, 20(22): 45-48.
16.	高文, 張曉慧, 張譯之, 等. 舒肝寧注射液對非酒精性脂肪性肝病組織工程肝保護作用的機制研究. 中西醫結合肝病雜志, 2022, 32(3): 248-251.
17.	陳元堃, 曾奧, 羅振輝, 等. β-谷甾醇藥理作用研究進展. 廣東藥科大學學報, 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, 湯威, 姜婧, 等. β-谷甾醇與豆甾醇對非酒精性脂肪肝作用的體外研究. 營養學報, 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.	錢坤, 劉亞云, 張艷, 等. 中藥抗非酒精性脂肪肝病分子機制的研究進展. 中草藥, 2020, 51(19): 5083-5092.
23.	艾正琳, 洪珊, 胡居龍, 等. 黃芩苷治療非酒精性脂肪性肝炎大鼠抗炎的療效. 山東大學學報(醫學版), 2019, 57(7): 55-60.
24.	馬納, 李亞靜, 范吉平. 金合歡素藥理研究進展. 中國現代應用藥學, 2018, 35(10): 1591-1595.
25.	甘璐, 孫曉春, 彭國平, 等. 刺槐素激活 PPARγ/NF-κB 通路改善高糖/高脂應激所致血管內皮細胞功能失調的研究. 藥品評價, 2023, 20(3): 294-298.
26.	阮雄中, 陳壓西. 代謝性炎癥與非酒精性脂肪性肝病的發生與發展. 中華消化雜志, 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.	陳聰, 周香輝, 張兵, 等. 基于網絡藥理學及計算機輔助藥物設計研究護肝寧片治療非酒精性脂肪性肝病的作用機制. 藥學學報, 2023, 58(3): 695-710.
29.	王寧, 李京濤, 常占杰, 等. PI3K/AKt 信號通路在胰島素抵抗所致非酒精性脂肪性肝病中作用機制的研究進展. 胃腸病學和肝病學雜志, 2019, 28(11): 1308-1311.
30.	馮帥霞, 徐瑩, 韓涵. 過氧化物酶體增殖物激活受體(PPAR)在肝臟疾病中的作用及潛在意義. 臨床肝膽病雜志, 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.	蘆建慧, 陳儉靜, 彭相文, 等. 非酒精性脂肪肝患者血清白介素-6 的檢測及意義. 中國現代醫學雜志, 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.	劉月白, 周義, 李昌平. 非酒精性脂肪性肝病中 MMP-9 作用的研究進展. 現代臨床醫學, 2019, 45(2): 81-83, 87.
36.	羅玲, 黃嘉璐, 楊子華, 等. 基于網絡藥理學和分子對接探討大花紅景天在 2 型糖尿病合并阿爾茨海默病中應用的潛在分子機制. 華西醫學, 2023, 38(4): 567-573.

1. 中華醫學會肝病學分會. 代謝相關(非酒精性)脂肪性肝病防治指南(2024 年版). 中華肝臟病雜志, 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. 中華中醫藥學會肝膽病分會. 非酒精性脂肪性肝炎中醫診療指南. 中西醫結合肝病雜志, 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. 舒肝寧注射液治療急性和慢性肝病共識專家委員會. 舒肝寧注射液治療急性和慢性肝病專家共識(2020 版). 中華實驗和臨床感染病雜志(電子版), 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. 張立娜, 張向宇, 朱雨晴, 等. 基于網絡藥理學探討舒肝寧注射液治療乙型病毒性肝炎的作用機制. 現代藥物與臨床, 2024, 39(3): 595-603.
8. 馬璐, 田國祥, 耿輝, 等. 中藥系統藥理數據庫 TCMSP 及其分析應用簡介. 中國循證心血管醫學雜志, 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. Pi?ero 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, Bou?as 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. 舒肝寧注射液聯合復方甘草酸苷對非酒精性脂肪性肝炎患者脂代謝、肝功能的影響. 中國醫學創新, 2023, 20(22): 45-48.
16. 高文, 張曉慧, 張譯之, 等. 舒肝寧注射液對非酒精性脂肪性肝病組織工程肝保護作用的機制研究. 中西醫結合肝病雜志, 2022, 32(3): 248-251.
17. 陳元堃, 曾奧, 羅振輝, 等. β-谷甾醇藥理作用研究進展. 廣東藥科大學學報, 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, 湯威, 姜婧, 等. β-谷甾醇與豆甾醇對非酒精性脂肪肝作用的體外研究. 營養學報, 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. 錢坤, 劉亞云, 張艷, 等. 中藥抗非酒精性脂肪肝病分子機制的研究進展. 中草藥, 2020, 51(19): 5083-5092.
23. 艾正琳, 洪珊, 胡居龍, 等. 黃芩苷治療非酒精性脂肪性肝炎大鼠抗炎的療效. 山東大學學報(醫學版), 2019, 57(7): 55-60.
24. 馬納, 李亞靜, 范吉平. 金合歡素藥理研究進展. 中國現代應用藥學, 2018, 35(10): 1591-1595.
25. 甘璐, 孫曉春, 彭國平, 等. 刺槐素激活 PPARγ/NF-κB 通路改善高糖/高脂應激所致血管內皮細胞功能失調的研究. 藥品評價, 2023, 20(3): 294-298.
26. 阮雄中, 陳壓西. 代謝性炎癥與非酒精性脂肪性肝病的發生與發展. 中華消化雜志, 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. 陳聰, 周香輝, 張兵, 等. 基于網絡藥理學及計算機輔助藥物設計研究護肝寧片治療非酒精性脂肪性肝病的作用機制. 藥學學報, 2023, 58(3): 695-710.
29. 王寧, 李京濤, 常占杰, 等. PI3K/AKt 信號通路在胰島素抵抗所致非酒精性脂肪性肝病中作用機制的研究進展. 胃腸病學和肝病學雜志, 2019, 28(11): 1308-1311.
30. 馮帥霞, 徐瑩, 韓涵. 過氧化物酶體增殖物激活受體(PPAR)在肝臟疾病中的作用及潛在意義. 臨床肝膽病雜志, 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. 蘆建慧, 陳儉靜, 彭相文, 等. 非酒精性脂肪肝患者血清白介素-6 的檢測及意義. 中國現代醫學雜志, 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. 劉月白, 周義, 李昌平. 非酒精性脂肪性肝病中 MMP-9 作用的研究進展. 現代臨床醫學, 2019, 45(2): 81-83, 87.
36. 羅玲, 黃嘉璐, 楊子華, 等. 基于網絡藥理學和分子對接探討大花紅景天在 2 型糖尿病合并阿爾茨海默病中應用的潛在分子機制. 華西醫學, 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

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