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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Study on the Mechanism of Dachaihu Decoction in the Treatment of Acute Pancreatitis Based on Artificial Intelligence Combined with in vivo Experiments

Author(s): Yan Zhang*, Sujie Li, Xiujiang Zhang, Pei Wang, Zhe Meng, Yuming Pang and Wei Li

Volume 26, Issue 13, 2023

Published on: 09 March, 2023

Page: [2345 - 2357] Pages: 13

DOI: 10.2174/1386207326666230202140740

Price: $65

Abstract

Background and Aim: To explore the possible mechanism of Dachaihu Decoction (DCHD) in the treatment of AP, and use in vivo experiments to verify.

Methods: The targets and active ingredients of DCHD in the treatment of AP were obtained through network pharmacology, and the preliminary verification was carried out by molecular docking. Caerulein was used to develop the AP rat model. H&E staining was performed to observe variations in pancreatic tissue. Western blot and RT-qPCR were conducted to evaluate the associated proteins and mRNA.

Results: The network pharmacology and molecular docking results showed that the key targets (EGFR, TNF, SRC, VEGFA and CTNNB1) and key active components (beta-sitosterol, stigmasterol, baicalein, quercetin, and kaempferol) of DCHD in the treatment of AP had good binding. H&E staining revealed that rat pancreatic tissues considerably damaged post caerulein intervention, and it has also been suggested that DCHD ameliorates damage to pancreatic tissue. Simultaneously, EGFR, TNF, SRC, VEGFA protein, and mRNA expression levels were increased in the model group compared to the blank group (P < 0.01), whereas CTNNB1 expression was found to be decreased in the model group (P < 0.01). Compared with the model group, the protein expression levels of EGFR, TNF, SRC, and VEGFA in the treatment group were down-regulated (P < 0.01), and CTNNB1 was up-regulated (P < 0.05).

Conclusion: DCHD protects pancreatic tissues and improves symptoms in AP rats by upregulating CTNNB1 protein and mRNA while inhibiting EGFR, TNF, SRC, and VEGFA protein and mRNA expression.

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[1]
Lankisch, P.G.; Apte, M.; Banks, P.A. Acute pancreatitis. Lancet, 2015, 386(9988), 85-96.
[http://dx.doi.org/10.1016/S0140-6736(14)60649-8] [PMID: 25616312]
[2]
Chiang, D.T.; Anozie, A.; Fleming, W.R.; Kiroff, G.K. Comparative study on acute pancreatitis management. ANZ J. Surg., 2004, 74(4), 218-221.
[http://dx.doi.org/10.1111/j.1445-2197.2004.02958.x] [PMID: 15043731]
[3]
Windsor, J.A.; Johnson, C.D.; Petrov, M.S.; Layer, P.; Garg, P.K.; Papachristou, G.I. Classifying the severity of acute pancreatitis: Towards a way forward. Pancreatology, 2015, 15(2), 101-104.
[http://dx.doi.org/10.1016/j.pan.2015.01.006] [PMID: 25683639]
[4]
Banerjee, A.K.; Kaul, A.; Bache, E.; Doran, J.; Nicholson, M.L. Multicentre audit of death from acute pancreatitis. Br. J. Surg., 2005, 81(10), 1541.
[http://dx.doi.org/10.1002/bjs.1800811048] [PMID: 7820498]
[5]
Tenner, S.; Baillie, J.; DeWitt, J.; Vege, S.S. American College of Gastroenterology guideline: management of acute pancreatitis. Am. J. Gastroenterol., 2013, 108(9), 1400-1415, 1416.
[http://dx.doi.org/10.1038/ajg.2013.218] [PMID: 23896955]
[6]
Su, Y.; Hong, Y.; Mei, F.; Wang, C.; Li, M.; Zhou, Y.; Zhao, K.; Yu, J.; Wang, W. High-fat diet aggravates the intestinal barrier injury via TLR4-RIP3 pathway in a rat model of severe acute pancreatitis. Mediators Inflamm., 2019, 2019, 1-13.
[http://dx.doi.org/10.1155/2019/2512687] [PMID: 31933540]
[7]
Yoshie, F.; Iizuka, A.; Komatsu, Y.; Matsumoto, A.; Itakura, H.; Kondo, K. Effects of Dai-saiko-to (Da-Chai-Hu-Tang) on plasma lipids and atherosclerotic lesions in female heterozygous heritable Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Pharmacol. Res., 2004, 50(3), 223-230.
[http://dx.doi.org/10.1016/j.phrs.2004.02.003] [PMID: 15225663]
[8]
Cheng, Y.X.; Wang, M.; Cheng, X. Effect of dachaihu decoction in treating acute mild pancreatitis of Gan-qi stagnant type. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih, 2008, 28(9), 793-796.
[PMID: 19065891]
[9]
Cui, H.; Li, Y.; Wang, Y.; Jin, L.; Yang, L.; Wang, L.; Liao, J.; Wang, H.; Peng, Y.; Zhang, Z.; Wang, H.; Liu, X. Da-Chai-Hu decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease through remodeling the gut microbiota and modulating the serum metabolism. Front. Pharmacol., 2020, 11, 584090.
[http://dx.doi.org/10.3389/fphar.2020.584090] [PMID: 33328987]
[10]
Duan, L.F.; Xu, X.F.; Zhu, L.J.; Liu, F.; Zhang, X.Q.; Wu, N.; Fan, J.W.; Xin, J.Q.; Zhang, H. Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis. World J. Gastroenterol., 2017, 23(40), 7242-7252.
[http://dx.doi.org/10.3748/wjg.v23.i40.7242] [PMID: 29142471]
[11]
Deng, S.; Gong, X.; Long, Z.; Bao, B.; Meng, F.; Feng, J.; Kuang, H.; Li, H.; Wang, B.; Wang, J. Xuefu Zhuyu decoction improves asthma‐induced asthenozoospermia based on network pharmacology and in vivo experiment. Andrologia, 2021, 53(10), e14198.
[http://dx.doi.org/10.1111/and.14198] [PMID: 34375006]
[12]
Guo, S.; Huang, Z.; Liu, X.; Zhang, J.; Ye, P.; Wu, C.; Lu, S.; Jia, S.; Zhang, X.; Chen, X.; Wang, M.; Wu, J. Biodata mining of differentially expressed genes between acute myocardial infarction and unstable angina based on integrated bioinformatics. BioMed Res. Int., 2021, 2021, 1-19.
[http://dx.doi.org/10.1155/2021/5584681] [PMID: 34568491]
[13]
Wang, J.; Gong, X.; Deng, S.; Meng, F.; Dai, H.; Bao, B.; Feng, J.; Li, H.; Wang, B. Effect of asthma on erectile dysfunction in rats as determined by biological network analysis. Med. Sci. Monit., 2020, 26, e927491.
[http://dx.doi.org/10.12659/MSM.927491] [PMID: 33341820]
[14]
Reagan-Shaw, S.; Nihal, M.; Ahmad, N. Dose translation from animal to human studies revisited. FASEB J., 2008, 22(3), 659-661.
[http://dx.doi.org/10.1096/fj.07-9574LSF] [PMID: 17942826]
[15]
Jeong, Y.; Lee, S.; Lim, J.; Kim, H. Docosahexaenoic acid inhibits cerulein-induced acute pancreatitis in rats. Nutrients, 2017, 9(7), 744.
[http://dx.doi.org/10.3390/nu9070744] [PMID: 28704954]
[16]
Hançerli, Y.; Kaplan, M.; Tanoğlu, A.; Yeşilbaş, S.; Küçükodacı, Z.; Yildirim, M.; Narli, G.; Sakin, Y.S. Efficacy of tocilizumab treatment in cerulein-induced experimental acute pancreatitis model in rats. Turk. J. Gastroenterol., 2017, 28(6), 485-491.
[http://dx.doi.org/10.5152/tjg.2017.16738] [PMID: 29086716]
[17]
Ding, S.P.; Li, J.C.; Jin, C. A mouse model of severe acute pancreatitis induced with caerulein and lipopolysaccharide. World J. Gastroenterol., 2003, 9(3), 584-589.
[http://dx.doi.org/10.3748/wjg.v9.i3.584] [PMID: 12632523]
[18]
Zhang, M.J.; Zhang, G.L.; Yuan, W.B.; Ni, J.; Huang, L.F. Treatment of abdominal compartment syndrome in severe acute pancreatitis patients with traditional Chinese medicine. World J. Gastroenterol., 2008, 14(22), 3574-3578.
[http://dx.doi.org/10.3748/wjg.14.3574] [PMID: 18567089]
[19]
Sakai, Y.; Masamune, A.; Satoh, A.; Nishihira, J.; Yamagiwa, T.; Shimosegawa, T. Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis. Gastroenterology, 2003, 124(3), 725-736.
[http://dx.doi.org/10.1053/gast.2003.50099] [PMID: 12612911]
[20]
Majidi, S.; Golembioski, A.; Wilson, S.L.; Thompson, E.C. Acute pancreatitis: Etiology, pathology, diagnosis, and treatment. South. Med. J., 2017, 110(11), 727-732.
[http://dx.doi.org/10.14423/SMJ.0000000000000727] [PMID: 29100225]
[21]
Li, J.; Zhang, S.; Zhou, R.; Zhang, J.; Li, Z.F. Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis. World J. Gastroenterol., 2017, 23(20), 3615-3623.
[http://dx.doi.org/10.3748/wjg.v23.i20.3615] [PMID: 28611514]
[22]
Zhao, G.; Zhuo, Y.Z.; Cui, L.H.; Li, C.X.; Chen, S.Y.; Li, D.; Liu, J.H.; Li, D.H.; Cui, N.Q.; Zhang, S.K. Modified Da-chai-hu Decoction regulates the expression of occludin and NF-κB to alleviate organ injury in severe acute pancreatitis rats. Chin. J. Nat. Med., 2019, 17(5), 355-362.
[http://dx.doi.org/10.1016/S1875-5364(19)30041-X] [PMID: 31171270]
[23]
Wodziak, D.; Dong, A.; Basin, M.F.; Lowe, A.W. Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) signaling is essential for murine pancreatitis-associated tissue regeneration. PLoS One, 2016, 11(10), e0164968.
[http://dx.doi.org/10.1371/journal.pone.0164968] [PMID: 27764193]
[24]
Engle, D.D.; Tiriac, H.; Rivera, K.D.; Pommier, A.; Whalen, S.; Oni, T.E.; Alagesan, B.; Lee, E.J.; Yao, M.A.; Lucito, M.S.; Spielman, B.; Da Silva, B.; Schoepfer, C.; Wright, K.; Creighton, B.; Afinowicz, L.; Yu, K.H.; Grützmann, R.; Aust, D.; Gimotty, P.A.; Pollard, K.S.; Hruban, R.H.; Goggins, M.G.; Pilarsky, C.; Park, Y.; Pappin, D.J.; Hollingsworth, M.A.; Tuveson, D.A. The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice. Science, 2019, 364(6446), 1156-1162.
[http://dx.doi.org/10.1126/science.aaw3145] [PMID: 31221853]
[25]
Ardito, C.M.; Grüner, B.M.; Takeuchi, K.K.; Lubeseder-Martellato, C.; Teichmann, N.; Mazur, P.K.; DelGiorno, K.E.; Carpenter, E.S.; Halbrook, C.J.; Hall, J.C.; Pal, D.; Briel, T.; Herner, A.; Trajkovic-Arsic, M.; Sipos, B.; Liou, G.Y.; Storz, P.; Murray, N.R.; Threadgill, D.W.; Sibilia, M.; Washington, M.K.; Wilson, C.L.; Schmid, R.M.; Raines, E.W.; Crawford, H.C.; Siveke, J.T. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell, 2012, 22(3), 304-317.
[http://dx.doi.org/10.1016/j.ccr.2012.07.024] [PMID: 22975374]
[26]
Malleo, G.; Mazzon, E.; Siriwardena, A.K.; Cuzzocrea, S. TNF-alpha as a therapeutic target in acute pancreatitis-lessons from experimental models. ScientificWorldJournal, 2007, 7, 431-448.
[http://dx.doi.org/10.1100/tsw.2007.98] [PMID: 17450307]
[27]
Hughes, C.B.; Grewal, H.P.; Gaber, L.W.; Kotb, M.; Mohey Eldin, A.B.; Mann, L.; Gaber, A.O. Anti-TNFα therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat. Am. J. Surg., 1996, 171(2), 274-280.
[http://dx.doi.org/10.1016/S0002-9610(97)89568-2] [PMID: 8619467]
[28]
Hartsock, A.; Nelson, W.J. Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton. Biochim. Biophys. Acta Biomembr., 2008, 1778(3), 660-669.
[http://dx.doi.org/10.1016/j.bbamem.2007.07.012] [PMID: 17854762]
[29]
Heller, R.S.; Dichmann, D.S.; Jensen, J.; Miller, C.; Wong, G.; Madsen, O.D.; Serup, P. Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation. Dev. Dyn., 2002, 225(3), 260-270.
[http://dx.doi.org/10.1002/dvdy.10157] [PMID: 12412008]
[30]
Huang, H.L.; Tang, G.D.; Liang, Z.H.; Qin, M.B.; Wang, X.M.; Chang, R.J.; Qin, H.P. Role of Wnt/β-catenin pathway agonist SKL2001 in Caerulein-induced acute pancreatitis. Can. J. Physiol. Pharmacol., 2019, 97(1), 15-22.
[http://dx.doi.org/10.1139/cjpp-2018-0226] [PMID: 30326193]
[31]
Nuche-Berenguer, B.; Ramos-Álvarez, I.; Jensen, R.T. Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion. Am. J. Physiol. Gastrointest. Liver Physiol., 2016, 310(11), G1015-G1027.
[http://dx.doi.org/10.1152/ajpgi.00349.2015] [PMID: 27033118]
[32]
Li, S.; Zhang, S.; Li, R.; Chen, S.; Chang, S.; Chen, X.; Li, Y.; Su, X.; Wu, T.; Xu, M. Prophylactic low-molecular-weight heparin administration protected against severe acute pancreatitis partially by VEGF/Flt-1 signaling in a rat model. Hum. Exp. Toxicol., 2020, 39(10), 1345-1354.
[http://dx.doi.org/10.1177/0960327120919469] [PMID: 32351125]
[33]
Yang, Q.; Yu, D.; Zhang, Y. β-Sitosterol attenuates the intracranial aneurysm growth by suppressing TNF-α-mediated mechanism. Pharmacology, 2019, 104(5-6), 303-311.
[http://dx.doi.org/10.1159/000502221] [PMID: 31473743]
[34]
Gupta, M.; Nath, R.; Srivastava, N.; Shanker, K.; Kishor, K.; Bhargava, K. Anti-inflammatory and antipyretic activities of beta-sitosterol. Planta Med., 1980, 39(6), 157-163.
[http://dx.doi.org/10.1055/s-2008-1074919] [PMID: 6967611]
[35]
Choi, J.N.; Choi, Y.H.; Lee, J.M.; Noh, I.C.; Park, J.W.; Choi, W.S.; Choi, J.H. Anti-inflammatory effects of β-sitosterol-β- D -glucoside from Trachelospermum jasminoides (Apocynaceae) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Nat. Prod. Res., 2012, 26(24), 2340-2343.
[http://dx.doi.org/10.1080/14786419.2012.654608] [PMID: 22292934]
[36]
Li, J.; Wu, Y.; Zhang, S.; Zhang, J.; Ji, F.; Bo, W.; Guo, X.; Li, Z. Baicalein protect pancreatic injury in rats with severe acute pancreatitis by inhibiting pro-inflammatory cytokines expression. Biochem. Biophys. Res. Commun., 2015, 466(4), 664-669.
[http://dx.doi.org/10.1016/j.bbrc.2015.09.094] [PMID: 26393905]
[37]
Pu, W.; Bai, R.; Zhou, K.; Peng, Y.; Zhang, M.; Hottiger, M.O.; Li, W.; Gao, X.; Sun, L. Baicalein attenuates pancreatic inflammatory injury through regulating MAPK, STAT 3 and NF-κB activation. Int. Immunopharmacol., 2019, 72, 204-210.
[http://dx.doi.org/10.1016/j.intimp.2019.04.018] [PMID: 30999210]
[38]
Junyuan, Z.; Hui, X.; Chunlan, H.; Junjie, F.; Qixiang, M.; Yingying, L.; Lihong, L.; Xingpeng, W.; Yue, Z. Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition. Pancreatology, 2018, 18(7), 742-752.
[http://dx.doi.org/10.1016/j.pan.2018.08.001] [PMID: 30115563]
[39]
Kim, S.H.; Park, J.G.; Sung, G.H.; Yang, S.; Yang, W.S.; Kim, E.; Kim, J.H.; Ha, V.T.; Kim, H.G.; Yi, Y.S.; Kim, J.H.; Baek, K.S.; Sung, N.Y.; Lee, M.; Kim, J.H.; Cho, J.Y. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain. Mol. Nutr. Food Res., 2015, 59(7), 1400-1405.
[http://dx.doi.org/10.1002/mnfr.201400820] [PMID: 25917334]
[40]
Antwi, A.O.; Obiri, D.D.; Osafo, N. Stigmasterol modulates allergic airway inflammation in guinea pig model of ovalbumin-induced asthma. Mediators Inflamm., 2017, 2017, 1-11.
[http://dx.doi.org/10.1155/2017/2953930] [PMID: 28555089]

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