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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Yantiao Formula Intervention in Rats with Sepsis: Network Pharmacology and Experimental Analysis

Author(s): Leilei Zhu, Deng Liu, Menghan Xu, Wenqing Wang, Xudong Xiong*, Qianmei Zhou* and Rong Shi*

Volume 27, Issue 7, 2024

Published on: 04 October, 2023

Page: [1071 - 1080] Pages: 10

DOI: 10.2174/0113862073262718230921113659

Price: $65

Abstract

Aim and Objective: Traditional Chinese Medicine prescribes Yantiao Formula (YTF; peach kernel, mirabilite, Angelica sinensis, Radix Scrophulariae, raw rhubarb, Radix Paeoniae, Flos Lonicerae, Forsythia, and Ophiopogon japonicus) to treat sepsis. Clinically, it reduced the inflammatory response of sepsis. It also reduced lung damage by decreasing the level of TNF-α in septic rats' serum. Using network pharmacology analysis, we investigated the efficacy network and mechanism of YTF in treating sepsis.

Materials and Methods: We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine (BATMAN-TCM) combined with literature to collect the main components in YTF and their targets. DisGeNET and GENECARDS databases were used for sepsis-related targets. Cytoscape 3.7.1 software was used to construct the herbcomponent- target and ingredient-target-disease interaction protein-protein interaction networks of YTF. The jvenn was used to perform the intersection of YTF targets and sepsis targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. We also created a sepsis rat model using cecal ligation and perforation and stimulated alveolar macrophages (NR8383) with endotoxin to investigate the mechanisms of YTF.

Results: GO, and KEGG enrichment analysis revealed that these targets involved mineralocorticoid secretion, aldosterone secretion, active regulation of chronic inflammatory response, the exogenous coagulation pathway, and other pathophysiology. It was linked to various inflammatory factors and the MAPK pathway. YTF inhibits the p38MAPK pathway and decreases TNF- α, IL-6, and CXCL8 levels.

Conclusion: YTF has a multi-component, multi-target, and multi-channel role in treating sepsis. The primary mechanisms may involve inhibiting the p38MAPK pathway to reduce the inflammatory response.

Keywords: Yantiao Formula, network pharmacology, sepsis, inflammatory reaction, p38MAPK pathway, inflammatory response.

Graphical Abstract
[1]
Rhodes, A.; Evans, L.E.; Alhazzani, W.; Levy, M.M.; Antonelli, M.; Ferrer, R.; Kumar, A.; Sevransky, J.E.; Sprung, C.L.; Nunnally, M.E.; Rochwerg, B.; Rubenfeld, G.D.; Angus, D.C.; Annane, D.; Beale, R.J.; Bellinghan, G.J.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.; De Backer, D.P.; French, C.J.; Fujishima, S.; Gerlach, H.; Hidalgo, J.L.; Hollenberg, S.M.; Jones, A.E.; Karnad, D.R.; Kleinpell, R.M.; Koh, Y.; Lisboa, T.C.; Machado, F.R.; Marini, J.J.; Marshall, J.C.; Mazuski, J.E.; McIntyre, L.A.; McLean, A.S.; Mehta, S.; Moreno, R.P.; Myburgh, J.; Navalesi, P.; Nishida, O.; Osborn, T.M.; Perner, A.; Plunkett, C.M.; Ranieri, M.; Schorr, C.A.; Seckel, M.A.; Seymour, C.W.; Shieh, L.; Shukri, K.A.; Simpson, S.Q.; Singer, M.; Thompson, B.T.; Townsend, S.R.; Van der Poll, T.; Vincent, J.L.; Wiersinga, W.J.; Zimmerman, J.L.; Dellinger, R.P. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med., 2017, 43(3), 304-377.
[http://dx.doi.org/10.1007/s00134-017-4683-6] [PMID: 28101605]
[2]
Ziaka, M.; Exadaktylos, A. ARDS associated acute brain injury: From the lung to the brain. Eur. J. Med. Res., 2022, 27(1), 150.
[http://dx.doi.org/10.1186/s40001-022-00780-2] [PMID: 35964069]
[3]
Miyashita, T.; Ahmed, A.K.; Nakanuma, S.; Okamoto, K.; Sakai, S.; Kinoshita, J.; Makino, I.; Nakamura, K.; Hayashi, H.; Oyama, K.; Tajima, H.; Takamura, H.; Ninomiya, I.; Fushida, S.; Harmon, J.W.; Ohta, T. A three-phase approach for the early identification of acute lung injury induced by severe sepsis. In Vivo, 2016, 30(4), 341-349.
[PMID: 27381595]
[4]
Wang, S.; Zheng, L.; Lyu, X. [Research progress on polarization regulation mechanism of alveolar macrophages in acute lung injury]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2020, 32(10), 1269-1272.
[PMID: 33198879]
[5]
Zhang, X.P.; Zhang, W.T.; Qiu, Y.; Ju, M.J.; Yang, C.; Tu, G.W.; Luo, Z. Cyclic helix B peptide alleviates sepsis-induced acute lung injury by downregulating NLRP3 inflammasome activation in alveolar macrophages. Int. Immunopharmacol., 2020, 88, 106849.
[http://dx.doi.org/10.1016/j.intimp.2020.106849] [PMID: 32795894]
[6]
Ding, H.; Yang, J.; Chen, L.; Li, Y.; Jiang, G.; Fan, J. Memantine alleviates acute lung injury via inhibiting macrophage pyroptosis. Shock, 2021, 56(6), 1040-1048.
[http://dx.doi.org/10.1097/SHK.0000000000001790] [PMID: 33882517]
[7]
Scozzi, D.; Liao, F.; Krupnick, A.S.; Kreisel, D.; Gelman, A.E. The role of neutrophil extracellular traps in acute lung injury. Front. Immunol., 2022, 13, 953195.
[http://dx.doi.org/10.3389/fimmu.2022.953195] [PMID: 35967320]
[8]
Iba, T; Levy, JH Inflammation and thrombosis: Roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. J. Thromb. Haemost., 2018, 16(2), 231-241.
[9]
Johnston, L.K.; Rims, C.R.; Gill, S.E.; McGuire, J.K.; Manicone, A.M. Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury. Am. J. Respir. Cell Mol. Biol., 2012, 47(4), 417-426.
[http://dx.doi.org/10.1165/rcmb.2012-0090OC] [PMID: 22721830]
[10]
Du, W.W.; Wang, X.X.; Zhang, D.; Chen, W.Q.; Zhang, X.L.; Li, P.M. Retrospective analysis on incidence and risk factors of early onset acute kidney injury after lung transplantation and its association with mortality. Ren. Fail., 2021, 43(1), 535-542.
[http://dx.doi.org/10.1080/0886022X.2021.1883652] [PMID: 33736580]
[11]
Luxen, M.; van Meurs, M.; Molema, G. Unlocking the untapped potential of endothelial kinase and phosphatase involvement in sepsis for drug treatment design. Front. Immunol., 2022, 13, 867625.
[http://dx.doi.org/10.3389/fimmu.2022.867625] [PMID: 35634305]
[12]
He, M.; Xiong, X.D.; Shen, X.H. Effects of Yantiao recipe on blood cytokines in patients with sepsis with acute respiratory distress syndrome (re-chi-yin-blood syndrome). Zhonghua Jizhen Yixue Zazhi, 2013, 22(07), 1097-1099.
[13]
Shi, R.; Xiong, X.D.; Li, S.F.; Wang, Q. The regulatory effect of factors. Zhonghua Jizhen Yixue Zazhi, 2012, 21(03), 397-398.
[14]
Shi, R.; Xiong, X.D. Activity changes and inflammation of NF-κB in the lung tissue of septic rats The effect of prescription on its activity. Shizhen Guo Yi Guo Yao, 2014, 25(04), 1016-1018.
[15]
Wang, Y.; Wang, X.; Li, Y.; Xue, Z.; Shao, R.; Li, L.; Zhu, Y.; Zhang, H.; Yang, J. Xuanfei baidu decoction reduces acute lung injury by regulating infiltration of neutrophils and macrophages via PD-1/IL17A pathway. Pharmacol. Res., 2022, 176, 106083.
[http://dx.doi.org/10.1016/j.phrs.2022.106083] [PMID: 35033647]
[16]
van der Poll, T.; Shankar-Hari, M.; Wiersinga, W.J. The immunology of sepsis. Immunity, 2021, 54(11), 2450-2464.
[http://dx.doi.org/10.1016/j.immuni.2021.10.012] [PMID: 34758337]
[17]
Patkova, A.; Joskova, V.; Havel, E.; Kovarik, M.; Kucharova, M.; Zadak, Z.; Hronek, M. Energy, protein, carbohydrate, and lipid intakes and their effects on morbidity and mortality in critically ill adult patients: A systematic review. Adv. Nutr., 2017, 8(4), 624-634.
[http://dx.doi.org/10.3945/an.117.015172] [PMID: 28710148]
[18]
Song, J.; Park, D.W.; Moon, S.; Cho, H.J.; Park, J.H.; Seok, H.; Choi, W.S. Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect. Dis., 2019, 19(1), 968.
[http://dx.doi.org/10.1186/s12879-019-4618-7] [PMID: 31718563]
[19]
Zhao, R.; Chen, M.; Jiang, Z.; Zhao, F.; Xi, B.; Zhang, X.; Fu, H.; Zhou, K. Platycodin-D induced autophagy in non-small cell lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathways. J. Cancer, 2015, 6(7), 623-631.
[http://dx.doi.org/10.7150/jca.11291] [PMID: 26078792]
[20]
Seternes, O.M.; Kidger, A.M.; Keyse, S.M. Dual-specificity MAP kinase phosphatases in health and disease. Biochim. Biophys. Acta Mol. Cell Res., 2019, 1866(1), 124-143.
[http://dx.doi.org/10.1016/j.bbamcr.2018.09.002] [PMID: 30401534]
[21]
Wang, H.; Sun, X.; Gao, F.; Zhong, B.; Zhang, Y.; Sun, Z. Effect of ulinastatin on growth inhibition, apoptosis of breast carcinoma cells is related to a decrease in signal conduction of JNk-2 and NF-κB. J. Exp. Clin. Cancer Res., 2012, 31(1), 2.
[http://dx.doi.org/10.1186/1756-9966-31-2] [PMID: 22217202]
[22]
Pizzino, G.; Bitto, A.; Pallio, G.; Irrera, N.; Galfo, F.; Interdonato, M.; Mecchio, A.; De Luca, F.; Minutoli, L.; Squadrito, F.; Altavilla, D. Blockade of the JNK signalling as a rational therapeutic approach to modulate the early and late steps of the inflammatory cascade in polymicrobial sepsis. Mediators Inflamm., 2015, 2015, 1-7.
[http://dx.doi.org/10.1155/2015/591572] [PMID: 25873765]
[23]
Mouasni, S.; Tourneur, L. FADD at the crossroads between cancer and inflammation. Trends Immunol., 2018, 39(12), 1036-1053.
[http://dx.doi.org/10.1016/j.it.2018.10.005] [PMID: 30401514]
[24]
Peyssonnaux, C.; Cejudo-Martin, P.; Doedens, A.; Zinkernagel, A.S.; Johnson, R.S.; Nizet, V. Cutting edge: Essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J. Immunol., 2007, 178(12), 7516-7519.
[http://dx.doi.org/10.4049/jimmunol.178.12.7516] [PMID: 17548584]
[25]
Bettelli, E.; Carrier, Y.; Gao, W.; Korn, T.; Strom, T.B.; Oukka, M.; Weiner, H.L.; Kuchroo, V.K. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 2006, 441(7090), 235-238.
[http://dx.doi.org/10.1038/nature04753] [PMID: 16648838]

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