Exploration of the potential mechanisms of Da Chaihu Decoction in treating acute pancreatitis based on network pharmacology and molecular docking_West China Medical Journal

Authors：

LUO Ke ^1,2 ,  TANG Huamin ¹

1. Emergency Department, Guangxi International Zhuang Medicine Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P. R. China;
2. Graduate School, Guangxi University of Chinese Medicine, Nanning, Guangxi 530201, P. R. China;

Corresponding?author：

TANG Huamin, Email: sam20041188@163.com

Keywords：

Acute pancreatitis; Da Chaihu Decoction; network pharmacology; molecular docking

DOI：

10.7507/1002-0179.202409008

Video：

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Objective To identify the therapeutic targets and molecular mechanisms of Da Chaihu Decoction in the treatment of acute pancreatitis (AP) based on network pharmacology and molecular docking. Methods From March to May 2024, the active compounds and targets of Da Chaihu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the targets related to AP were obtained from the GeneCards database. The intersection of these yielded the common targets of Da Chaihu Decoction for AP treatment. The STRING platform was used to construct a protein-protein interaction network, and Cytoscape 3.9.1 software was employed for network topology analysis to identify core targets and compounds. The Metascape platform was applied for gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, with bubble charts generated using Python 3.8 software. Molecular docking was conducted using AutoDock 1.5.6 software to predict binding affinities between core compounds and targets. Results A total of 84 common targets of Da Chaihu Decoction for AP treatment were identified. The core compounds included quercetin, β-sitosterol, kaempferol, luteolin, and baicalein. The key proteins included AKT1, B-cell leukemia/lymphoma 2 (BCL2), Jun proto-oncogene (JUN), interleukin 1 Beta (IL1B), and nuclear factor kappa B subunit 1 (NFKB1), all of which were enriched in pathways such as lipid and atherosclerosis, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and apoptosis. The binding energies of some core compounds with key proteins were below –5.0 kJ/mol. Conclusion Da Chaihu Decoction may exert anti-inflammatory and anti-apoptotic effects in AP by modulating key protein targets, including AKT1, BCL2, JUN, IL1B, and NFKB1, within pathways such as lipid and atherosclerosis, PI3K-Akt signaling, MAPK signaling, TNF signaling, and apoptosis.

Citation： LUO Ke, TANG Huamin. Exploration of the potential mechanisms of Da Chaihu Decoction in treating acute pancreatitis based on network pharmacology and molecular docking. West China Medical Journal, 2024, 39(11): 1728-1737. doi: 10.7507/1002-0179.202409008 Copy

1.	Samarasekera E, Mahammed S, Carlisle S, et al. Pancreatitis: summary of NICE guidance. BMJ, 2018, 362: k3443.
2.	郭嚴, 陳東風, 孫文靜. CT 評估人體脂肪面積與急性高脂血癥性胰腺炎復發的相關性研究. 第三軍醫大學學報, 2019, 41(14): 1370-1373.
3.	王倩倩, 周健, 江志偉, 等. 急性胰腺炎患者中醫體質及證型分布特點研究. 中國中西醫結合雜志, 2021, 41(8): 917-921.
4.	洪日, 陳昫, 范文雯, 等. 基于長桑君脈息法應用大柴胡湯辨治急性胰腺炎經驗. 中華中醫藥雜志, 2022, 37(10): 5783-5786.
5.	周靜, 陸賢燕. 加減大柴胡湯治療急性胰腺炎的臨床療效分析. 現代醫學與健康研究電子雜志, 2023, 7(12): 95-97.
6.	趙越. 大柴胡湯的方證研究. 長春: 長春中醫藥大學, 2022.
7.	胡長順, 沈友虎, 宋明霞, 等. 胡希恕教授臨床應用大柴胡湯經驗. 中國社區醫師, 2021, 37(1): 64-65, 68.
8.	王晨輝, 何兵麗, 胡仕祥. 大柴胡湯治療急性胰腺炎作用機制的研究進展. 中國中醫急癥, 2024, 33(9): 1681-1684.
9.	孟凡翠, 湯立達. 中藥網絡藥理學研究中存在的問題與發展展望. 中草藥, 2020, 51(8): 2232-2237.
10.	Luo C, Huang Q, Yuan X, et al. Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway. Apoptosis, 2020, 25(3/4): 290-303.
11.	Manohar M, Verma AK, Venkateshaiah SU, et al. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther, 2017, 8(1): 10-25.
12.	Malleo G, Mazzon E, Siriwardena AK, et al. Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis to clinical evidence. Shock, 2007, 28(2): 130-140.
13.	Zhang XP, Lin Q, Zhou YF. Progress of study on the relationship between mediators of inflammation and apoptosis in acute pancreatitis. Dig Dis Sci, 2007, 52(5): 1199-1205.
14.	Frossard JL, Pastor CM. Experimental acute pancreatitis: new insights into the pathophysiology. Front Biosci, 2002, 7: d275-d287.
15.	苗明三, 王升啟. 現代方劑學—藥理與臨床. 北京: 清華大學出版社, 2004: 510-514.
16.	Liu J, Li X, Yue Y, et al. The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophils. Cell Mol Immunol, 2005, 2(6): 455-460.
17.	Cheng SC, Huang WC, S Pang JH, et al. Quercetin inhibits the production of IL-1β-induced inflammatory cytokines and chemokines in ARPE-19 cells via the MAPK and NF-κB signaling pathways. Int J Mol Sci, 2019, 20(12): 2957.
18.	Paniagua-Pérez R, Flores-Mondragón G, Reyes-Legorreta C, et al. Evaluation of the anti-inflammatory capacity of beta-sitosterol in rodent assays. Afr J Tradit Complement Altern Med, 2016, 14(1): 123-130.
19.	Fraile L, Crisci E, Córdoba L, et al. Immunomodulatory properties of beta-sitosterol in pig immune responses. Int Immunopharmacol, 2012, 13(3): 316-321.
20.	Tian CL, Liu X, Chang Y, et al. Investigation of the anti-inflammatory and antioxidant activities of luteolin, kaempferol, apigenin and quercetin. S Afr J Bot, 2021, 137: 257-264.
21.	Kadioglu O, Nass J, Saeed ME, et al. Kaempferol is an anti-inflammatory compound with activity towards NF-κB pathway proteins. Anticancer Res, 2015, 35(5): 2645-2650.
22.	Conti P, Caraffa A, Gallenga CE, et al. Powerful anti-inflammatory action of luteolin: Potential increase with IL-38. Biofactors, 2021, 47(2): 165-169.
23.	Wang S, Cao M, Xu S, et al. Luteolin alters macrophage polarization to inhibit inflammation. Inflammation, 2020, 43(1): 95-108.
24.	Chen S, Yang Y, Feng H, et al. Baicalein inhibits interleukin-1β-induced proliferation of human rheumatoid arthritis fibroblast-like synoviocytes. Inflammation, 2014, 37(1): 163-169.
25.	Chen C, Zhang C, Cai L, et al. Baicalin suppresses IL-1β-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models. Int Immunopharmacol, 2017, 52: 218-226.
26.	Chen R, Malagola E, Dietrich M, et al. Akt1 signalling supports acinar proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis. J Pathol, 2020, 250(1): 42-54.
27.	Sung KF, Odinokova IV, Mareninova OA, et al. Prosurvival Bcl-2 proteins stabilize pancreatic mitochondria and protect against necrosis in experimental pancreatitis. Exp Cell Res, 2009, 315(11): 1975-1989.
28.	Choi SB, Bae GS, Jo IJ, et al. Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways. Mol Immunol, 2016, 74: 27-38.
29.	Szatmary P, Gukovsky I. The role of cytokines and inflammation in the genesis of experimental pancreatitis. Pancreapedia, 2016.
30.	Sendler M, van den Brandt C, Glaubitz J, et al. NLRP3 inflammasome regulates development of systemic inflammatory response and compensatory anti-inflammatory response syndromes in mice with acute pancreatitis. Gastroenterology, 2020, 158(1): 253-269.
31.	Sarker RS, Steiger K. A critical role for Akt1 signaling in acute pancreatitis progression. J Pathol, 2020, 251(1): 1-3.
32.	Ma R, Chen C, Wang Z, et al. Causal relationship between plasma lipidome and four types of pancreatitis: a bidirectional Mendelian randomization study. Front Endocrinol (Lausanne), 2024, 5: 1415474.
33.	Liu HS, Pan CE, Liu QG, et al. Effect of NF-kappaB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis. World J Gastroenterol, 2003, 9(11): 2513-2518.
34.	Bhatia M. Apoptosis of pancreatic acinar cells in acute pancreatitis: is it good or bad?. J Cell Mol Med, 2004, 8(3): 402-409.

1. Samarasekera E, Mahammed S, Carlisle S, et al. Pancreatitis: summary of NICE guidance. BMJ, 2018, 362: k3443.
2. 郭嚴, 陳東風, 孫文靜. CT 評估人體脂肪面積與急性高脂血癥性胰腺炎復發的相關性研究. 第三軍醫大學學報, 2019, 41(14): 1370-1373.
3. 王倩倩, 周健, 江志偉, 等. 急性胰腺炎患者中醫體質及證型分布特點研究. 中國中西醫結合雜志, 2021, 41(8): 917-921.
4. 洪日, 陳昫, 范文雯, 等. 基于長桑君脈息法應用大柴胡湯辨治急性胰腺炎經驗. 中華中醫藥雜志, 2022, 37(10): 5783-5786.
5. 周靜, 陸賢燕. 加減大柴胡湯治療急性胰腺炎的臨床療效分析. 現代醫學與健康研究電子雜志, 2023, 7(12): 95-97.
6. 趙越. 大柴胡湯的方證研究. 長春: 長春中醫藥大學, 2022.
7. 胡長順, 沈友虎, 宋明霞, 等. 胡希恕教授臨床應用大柴胡湯經驗. 中國社區醫師, 2021, 37(1): 64-65, 68.
8. 王晨輝, 何兵麗, 胡仕祥. 大柴胡湯治療急性胰腺炎作用機制的研究進展. 中國中醫急癥, 2024, 33(9): 1681-1684.
9. 孟凡翠, 湯立達. 中藥網絡藥理學研究中存在的問題與發展展望. 中草藥, 2020, 51(8): 2232-2237.
10. Luo C, Huang Q, Yuan X, et al. Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway. Apoptosis, 2020, 25(3/4): 290-303.
11. Manohar M, Verma AK, Venkateshaiah SU, et al. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther, 2017, 8(1): 10-25.
12. Malleo G, Mazzon E, Siriwardena AK, et al. Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis to clinical evidence. Shock, 2007, 28(2): 130-140.
13. Zhang XP, Lin Q, Zhou YF. Progress of study on the relationship between mediators of inflammation and apoptosis in acute pancreatitis. Dig Dis Sci, 2007, 52(5): 1199-1205.
14. Frossard JL, Pastor CM. Experimental acute pancreatitis: new insights into the pathophysiology. Front Biosci, 2002, 7: d275-d287.
15. 苗明三, 王升啟. 現代方劑學—藥理與臨床. 北京: 清華大學出版社, 2004: 510-514.
16. Liu J, Li X, Yue Y, et al. The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophils. Cell Mol Immunol, 2005, 2(6): 455-460.
17. Cheng SC, Huang WC, S Pang JH, et al. Quercetin inhibits the production of IL-1β-induced inflammatory cytokines and chemokines in ARPE-19 cells via the MAPK and NF-κB signaling pathways. Int J Mol Sci, 2019, 20(12): 2957.
18. Paniagua-Pérez R, Flores-Mondragón G, Reyes-Legorreta C, et al. Evaluation of the anti-inflammatory capacity of beta-sitosterol in rodent assays. Afr J Tradit Complement Altern Med, 2016, 14(1): 123-130.
19. Fraile L, Crisci E, Córdoba L, et al. Immunomodulatory properties of beta-sitosterol in pig immune responses. Int Immunopharmacol, 2012, 13(3): 316-321.
20. Tian CL, Liu X, Chang Y, et al. Investigation of the anti-inflammatory and antioxidant activities of luteolin, kaempferol, apigenin and quercetin. S Afr J Bot, 2021, 137: 257-264.
21. Kadioglu O, Nass J, Saeed ME, et al. Kaempferol is an anti-inflammatory compound with activity towards NF-κB pathway proteins. Anticancer Res, 2015, 35(5): 2645-2650.
22. Conti P, Caraffa A, Gallenga CE, et al. Powerful anti-inflammatory action of luteolin: Potential increase with IL-38. Biofactors, 2021, 47(2): 165-169.
23. Wang S, Cao M, Xu S, et al. Luteolin alters macrophage polarization to inhibit inflammation. Inflammation, 2020, 43(1): 95-108.
24. Chen S, Yang Y, Feng H, et al. Baicalein inhibits interleukin-1β-induced proliferation of human rheumatoid arthritis fibroblast-like synoviocytes. Inflammation, 2014, 37(1): 163-169.
25. Chen C, Zhang C, Cai L, et al. Baicalin suppresses IL-1β-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models. Int Immunopharmacol, 2017, 52: 218-226.
26. Chen R, Malagola E, Dietrich M, et al. Akt1 signalling supports acinar proliferation and limits acinar-to-ductal metaplasia formation upon induction of acute pancreatitis. J Pathol, 2020, 250(1): 42-54.
27. Sung KF, Odinokova IV, Mareninova OA, et al. Prosurvival Bcl-2 proteins stabilize pancreatic mitochondria and protect against necrosis in experimental pancreatitis. Exp Cell Res, 2009, 315(11): 1975-1989.
28. Choi SB, Bae GS, Jo IJ, et al. Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways. Mol Immunol, 2016, 74: 27-38.
29. Szatmary P, Gukovsky I. The role of cytokines and inflammation in the genesis of experimental pancreatitis. Pancreapedia, 2016.
30. Sendler M, van den Brandt C, Glaubitz J, et al. NLRP3 inflammasome regulates development of systemic inflammatory response and compensatory anti-inflammatory response syndromes in mice with acute pancreatitis. Gastroenterology, 2020, 158(1): 253-269.
31. Sarker RS, Steiger K. A critical role for Akt1 signaling in acute pancreatitis progression. J Pathol, 2020, 251(1): 1-3.
32. Ma R, Chen C, Wang Z, et al. Causal relationship between plasma lipidome and four types of pancreatitis: a bidirectional Mendelian randomization study. Front Endocrinol (Lausanne), 2024, 5: 1415474.
33. Liu HS, Pan CE, Liu QG, et al. Effect of NF-kappaB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis. World J Gastroenterol, 2003, 9(11): 2513-2518.
34. Bhatia M. Apoptosis of pancreatic acinar cells in acute pancreatitis: is it good or bad?. J Cell Mol Med, 2004, 8(3): 402-409.

West China Medical Journal

Exploration of the potential mechanisms of Da Chaihu Decoction in treating acute pancreatitis based on network pharmacology and molecular docking

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