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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Elucidating the Mechanism of Buyanghuanwu Decoction Acting on Pulmonary Fibrosis Based on Network Pharmacology and Animal Studies

Author(s): Qichang Xing*, Xiang Liu*, Zheng Liu, Qingzi Yan, Yixiang Hu, Wencan Li and Ke Peng

Volume 27, Issue 7, 2024

Published on: 04 September, 2023

Page: [1046 - 1055] Pages: 10

DOI: 10.2174/1386207326666230823093958

Price: $65

Abstract

Background and Objective: Buyanghuanwu Decoction (BYHWD) is a clinically proven prescription effective in treating pulmonary fibrosis (PF), but the molecular mechanism underlying its action remains unclear. The network pharmacology analysis was performed to elucidate the acting substances and related pathways of BYHWD in treating bleomycin (BLM) induced PF mouse.

Methods: First, the pharmacologically active components and corresponding targets in BYHWD were identified through the TCMSP database and literature review. Second, PF-related targets were identified through the DisGeNet database. Then, the components-targets network of BYHWD in PF treatment was constructed using Cytoscape. The DAVID database was used for the enrichment analysis of GO terms and KEGG pathways. At last, the therapeutic effect of BYHWD on BLMinduced PF mice were verified, and the mRNA and protein expression of related targets was determined through RT-PCR and western blotting, respectively.

Results: The core component-target network contained 58 active components and 147 targets. Thirty-nine core targets were mainly involved in the regulation of biological functions and KEGG pathways, such as the positive regulation of nitric oxide biosynthesis and the TNF signaling pathway. These core targets were obtained through enrichment analysis. Moreover, animal studies revealed that BYHWD down-regulated the mRNA expression levels of TNF, IL-6, IL-1β, and NOS2 and inhibited NF-κB and p38 phosphorylation.

Conclusion: The effects of BYHWD on PF mice are therapeutic, and its anti-PF mechanism mainly involves the effects on inflammatory factors and the NF-κB/p38 pathway.

Graphical Abstract

[1]
Kaur, A.; Mathai, S.K.; Schwartz, D.A. Genetics in idiopathic pulmonary fibrosis pathogenesis, prognosis, and treatment. Front. Med., 2017, 4, 154.
[http://dx.doi.org/10.3389/fmed.2017.00154] [PMID: 28993806]
[2]
Hutchinson, J.; Fogarty, A.; Hubbard, R.; McKeever, T. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur. Respir. J., 2015, 46(3), 795-806.
[http://dx.doi.org/10.1183/09031936.00185114] [PMID: 25976683]
[3]
Nalysnyk, L.; Cid-Ruzafa, J.; Rotella, P.; Esser, D. Incidence and prevalence of idiopathic pulmonary fibrosis: Review of the literature. Eur. Respir. Rev., 2012, 21(126), 355-361.
[http://dx.doi.org/10.1183/09059180.00002512] [PMID: 23204124]
[4]
Jiang, H.Y.; Yang, H.; Dai, Q.; Wu, X.H.; Tanghao, Y.N.; Wang, F.; Du, Q.Y. Clinical trial of buyang huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis. Zhongguo Shiyan Fangjixue Zazhi, 2022, 28(21), 104-111.
[5]
Xiao, M.F.; Liu, J.L.; Yang, Y.T.; Liu, W.L.; Deng, K.W. Current research situation of Buyang Huanwu Decoction and its development of new medical invention. Chin. Tradit. Herbal Drugs, 2018, 49(7), 1688-1694.
[6]
Chen, H.; Song, H.; Liu, X.; Tian, J.; Tang, W.; Cao, T.; Zhao, P.; Zhang, C.; Guo, W.; Xu, M.; Lu, R. Buyanghuanwu Decoction alleviated pressure overload induced cardiac remodeling by suppressing Tgf-β/Smads and MAPKs signaling activated fibrosis. Biomed. Pharmacother., 2017, 95, 461-468.
[http://dx.doi.org/10.1016/j.biopha.2017.08.102] [PMID: 28865366]
[7]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[8]
Huang, J.W.; Gao, H.W.; Duan, J.F. Research on chemical composition and pharmacological effects of geosaurus. Guiding J. Tradit. Chin. Med. Pharm., 2018, 12(24), 104-107.
[9]
Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839.
[http://dx.doi.org/10.1093/nar/gkw943] [PMID: 27924018]
[10]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[11]
Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C. STRING v11: Protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019, 47(D1), D607-D613.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[12]
Dennis, G., Jr; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol., 2003, 4(5), P3.
[http://dx.doi.org/10.1186/gb-2003-4-5-p3] [PMID: 12734009]
[13]
Li, X.H.; Xiao, T.; Yang, J.H.; Qin, Y.; Gao, J.J.; Liu, H.J.; Zhou, H.G. Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway. Respir. Res., 2018, 19(1), 111.
[14]
Ashcroft, T.; Simpson, J.M.; Timbrell, V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J. Clin. Pathol., 1988, 41(4), 467-470.
[PMID: 3366935]
[15]
Zhang, Y.; Lu, P.; Qin, H.; Zhang, Y.; Sun, X.; Song, X.; Liu, J.; Peng, H.; Liu, Y.; Nwafor, E.O.; Li, J.; Liu, Z. Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis: Rationale and therapeutic potential. Biomed. Pharmacother., 2021, 133111072.
[http://dx.doi.org/10.1016/j.biopha.2020.111072] [PMID: 33378971]
[16]
Xin, L.L.; Jiang, M.; Zhang, G.; Gong, J.N. [Efficacy and safety of Danhong injection for idiopathic pulmonary fibrosis: Meta-analysis]. Zhongguo Zhongyao Zazhi, 2016, 41(20), 3859-3865.
[PMID: 28929667]
[17]
Yu, X.; Yang, S.; Xie, Y.; Li, J. Traditional Chinese medicine in the treatment of idiopathic pulmonary fibrosis based on syndrome differentiation: Study protocol of an exploratory trial. J. Integr. Med., 2020, 18(2), 163-168.
[http://dx.doi.org/10.1016/j.joim.2019.12.005] [PMID: 31928920]
[18]
Yu, X.; Zhang, Y.; Yang, X.; Zhang, X.; Wang, X.; Liu, X.; Yan, Y. The influence of buqihuoxuetongluo formula on histopathology and pulmonary function test in bleomycin-induced idiopathic pulmonary fibrosis in rats. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-13.
[http://dx.doi.org/10.1155/2018/8903021] [PMID: 30046348]
[19]
Huang, H.; Peng, X.; Zhong, C. Idiopathic pulmonary fibrosis: The current status of its epidemiology, diagnosis, and treatment in China. Intractable Rare Dis. Res., 2013, 2(3), 88-93.
[http://dx.doi.org/10.5582/irdr.2013.v2.3.88] [PMID: 25343109]
[20]
Yang, Y.; Zengtao, S.; Liqing, S.; Yanping, Z.; Zhaoshan, Z.; Shunan, Z.; Enxiang, C. Effects of Feiwei granules in the treatment of idiopathic pulmonary fibrosis: a randomized and placebo-controlled trial. J. Tradit. Chin. Med., 2016, 36(4), 427-433.
[http://dx.doi.org/10.1016/S0254-6272(16)30058-9] [PMID: 28459237]
[21]
Zhang, S.; Wu, H.; Liu, J.; Gu, H.; Li, X.; Zhang, T. Medication regularity of pulmonary fibrosis treatment by contemporary traditional Chinese medicine experts based on data mining. J. Thorac. Dis., 2018, 10(3), 1775-1787.
[http://dx.doi.org/10.21037/jtd.2018.03.11] [PMID: 29707332]
[22]
Li, C.; Zhang, W.J.; Frei, B. Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol., 2016, 9, 104-113.
[http://dx.doi.org/10.1016/j.redox.2016.06.006] [PMID: 27454768]
[23]
Boots, A.W.; Veith, C.; Albrecht, C.; Bartholome, R.; Drittij, M.J.; Claessen, S.M.H.; Bast, A.; Rosenbruch, M.; Jonkers, L.; van Schooten, F.J.; Schins, R.P.F. The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice. BMC Pulm. Med., 2020, 20(1), 112.
[http://dx.doi.org/10.1186/s12890-020-1142-x] [PMID: 32349726]
[24]
Ulusoy, H.G.; Sanlier, N. A minireview of quercetin: from its metabolism to possible mechanisms of its biological activities. Crit. Rev. Food Sci. Nutr., 2020, 60(19), 3290-3303.
[http://dx.doi.org/10.1080/10408398.2019.1683810] [PMID: 31680558]
[25]
Aziz, N.; Kim, M.Y.; Cho, J.Y. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J. Ethnopharmacol., 2018, 225, 342-358.
[http://dx.doi.org/10.1016/j.jep.2018.05.019] [PMID: 29801717]
[26]
Liu, H.; Yu, H.; Cao, Z.; Gu, J.; Pei, L.; Jia, M.; Su, M. Kaempferol modulates autophagy and alleviates silica-induced pulmonary fibrosis. DNA Cell Biol., 2019, 38(12), 1418-1426.
[http://dx.doi.org/10.1089/dna.2019.4941] [PMID: 31560574]
[27]
Liang, Q.; Cai, W.; Zhao, Y.; Xu, H.; Tang, H.; Chen, D.; Qian, F.; Sun, L. Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis. Pharmacol. Res., 2020, 158104884.
[http://dx.doi.org/10.1016/j.phrs.2020.104884] [PMID: 32428667]
[28]
Li, C.; Sun, X.; Li, A.; Mo, M.; Zhao, Z. S-Allylmercaptocysteine attenuates Bleomycin-induced pulmonary fibrosis in mice via suppressing TGF-β1/Smad and oxidative stress pathways. Int. Immunopharmacol., 2020, 79106110.
[http://dx.doi.org/10.1016/j.intimp.2019.106110] [PMID: 31874367]
[29]
Malaviya, R.; Laskin, J.D.; Laskin, D.L. Anti-TNFα therapy in inflammatory lung diseases. Pharmacol. Ther., 2017, 180, 90-98.
[http://dx.doi.org/10.1016/j.pharmthera.2017.06.008] [PMID: 28642115]
[30]
Epstein Shochet, G.; Bardenstein-Wald, B.; McElroy, M.; Kukuy, A.; Surber, M.; Edelstein, E.; Pertzov, B.; Kramer, M.R.; Shitrit, D. Hypoxia Inducible Factor 1A Supports a Pro-Fibrotic Phenotype Loop in Idiopathic Pulmonary Fibrosis. Int. J. Mol. Sci., 2021, 22(7), 3331.
[http://dx.doi.org/10.3390/ijms22073331] [PMID: 33805152]
[31]
Mukhopadhyay, S.; Hoidal, J.R.; Mukherjee, T.K. Role of TNFα in pulmonary pathophysiology. Respir. Res., 2006, 7(1), 125.
[http://dx.doi.org/10.1186/1465-9921-7-125] [PMID: 17034639]
[32]
Gad, E.S.; Salama, A.A.A.; El-Shafie, M.F.; Arafa, H.M.M.; Abdelsalam, R.M.; Khattab, M. The anti-fibrotic and anti-inflammatory potential of bone marrow–derived mesenchymal stem cells and nintedanib in bleomycin-induced lung fibrosis in rats. Inflammation, 2020, 43(1), 123-134.
[http://dx.doi.org/10.1007/s10753-019-01101-2] [PMID: 31646446]
[33]
Liu, P.; Yang, S.; Wang, Z.; Dai, H.; Wang, C. Feasibility and mechanism analysis of shenfu injection in the treatment of idiopathic pulmonary fibrosis. Front. Pharmacol., 2021, 12670146.
[http://dx.doi.org/10.3389/fphar.2021.670146] [PMID: 34393772]
[34]
Lappalainen, U.; Whitsett, J.A.; Wert, S.E.; Tichelaar, J.W.; Bry, K. Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am. J. Respir. Cell Mol. Biol., 2005, 32(4), 311-318.
[http://dx.doi.org/10.1165/rcmb.2004-0309OC] [PMID: 15668323]
[35]
Chung, M.P.; Monick, M.M.; Hamzeh, N.Y.; Butler, N.S.; Powers, L.S.; Hunninghake, G.W. Role of repeated lung injury and genetic background in bleomycin-induced fibrosis. Am. J. Respir. Cell Mol. Biol., 2003, 29(3), 375-380.
[http://dx.doi.org/10.1165/rcmb.2003-0029OC] [PMID: 12676806]
[36]
Noguchi, S.; Yatera, K.; Wang, K.Y.; Oda, K.; Akata, K.; Yamasaki, K.; Kawanami, T.; Ishimoto, H.; Toyohira, Y.; Shimokawa, H.; Yanagihara, N.; Tsutsui, M.; Mukae, H. Nitric oxide exerts protective effects against bleomycin-induced pulmonary fibrosis in mice. Respir. Res., 2014, 15(1), 92.
[http://dx.doi.org/10.1186/s12931-014-0092-3] [PMID: 25092105]

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