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


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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.

About the authors

Leilei Zhu

, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Email: info@benthamscience.net

Deng Liu

, Shanghai University of Traditional Chinese Medicine

Email: info@benthamscience.net

Menghan Xu

, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Email: info@benthamscience.net

Wenqing Wang

, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Email: info@benthamscience.net

Xudong Xiong

, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

Qianmei Zhou

, Shanghai University of Traditional Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

Rong Shi

, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

References

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1038/nature04753 PMID: 16648838

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