Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Bei Li; Yong Zhang; Xinyuan Liu; Ziyang Zhang; Shuqing Zhuang; Xiaoli Zhong; Wenbo Chen; Yilin Hong; Pingli Mo; Shuhai Lin; Shicong Wang; Chundong Yu

doi:10.1016/j.jpha.2023.12.005

Volume 14 Issue 4

Apr. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(4): 100915

Bei Li, Yong Zhang, Xinyuan Liu, Ziyang Zhang, Shuqing Zhuang, Xiaoli Zhong, Wenbo Chen, Yilin Hong, Pingli Mo, Shuhai Lin, Shicong Wang, Chundong Yu. Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling[J]. Journal of Pharmaceutical Analysis, 2024, 14(4): 100915. doi: 10.1016/j.jpha.2023.12.005

Citation:

Bei Li, Yong Zhang, Xinyuan Liu, Ziyang Zhang, Shuqing Zhuang, Xiaoli Zhong, Wenbo Chen, Yilin Hong, Pingli Mo, Shuhai Lin, Shicong Wang, Chundong Yu. Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling[J]. Journal of Pharmaceutical Analysis, 2024, 14(4): 100915. doi: 10.1016/j.jpha.2023.12.005

Citation:

Bei Li, Yong Zhang, Xinyuan Liu, Ziyang Zhang, Shuqing Zhuang, Xiaoli Zhong, Wenbo Chen, Yilin Hong, Pingli Mo, Shuhai Lin, Shicong Wang, Chundong Yu. Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling[J]. Journal of Pharmaceutical Analysis, 2024, 14(4): 100915. doi: 10.1016/j.jpha.2023.12.005

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Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

doi: 10.1016/j.jpha.2023.12.005

a. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China;
b. Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou, Fujian, 363000, China;
c. Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, China;
d. Department of Cardiology, Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China

Funds:

This work was supported by research funds from Zhangzhou Pien Tze Huang Pharmaceutical Co. Ltd (Grant Nos.: 437b8f31, d6092dae, and YHT-19064 to Chundong Yu), the National Natural Science Foundation of China (Grant Nos.: 81970485 and 82173086 to Chundong Yu), and the Natural Science Foundation of Fujian Province (Grant No.: 2023J01249 to Shicong Wang).

Received Date: Aug. 20, 2023
Accepted Date: Dec. 07, 2023
Rev Recd Date: Nov. 22, 2023
Publish Date: Dec. 10, 2023

Abstract

Abstract

Pien Tze Huang (PZH), a class-1 nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
- Pien Tze Huang,
- Bile acids,
- Sepsis,
- Inflammation,
- TGR5,
- STAT3-A20 signalling

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References(45)

References

[1]	M. Cecconi, L. Evans, M. Levy, et al., Sepsis and septic shock, Lancet 392 (2018) 75-87.
[2]	J.D. Faix, Biomarkers of sepsis, Crit. Rev. Clin. Lab. Sci. 50 (2013) 23-36.
[3]	N.K. Adhikari, R.A. Fowler, S. Bhagwanjee, et al., Critical care and the global burden of critical illness in adults, Lancet 376 (2010) 1339-1346.
[4]	D.C. Angus, W.T. Linde-Zwirble, J. Lidicker, et al., Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care, Crit. Care Med. 29 (2001) 1303-1310.
[5]	F.B. Mayr, S. Yende, and D.C. Angus, Epidemiology of severe sepsis, Virulence 5 (2014) 4-11.
[6]	X. Chen and D. Song, LPS promotes the progression of sepsis by activation of lncRNA HULC/miR-204-5p/TRPM7 network in HUVECs, Biosci. Rep. 40 (2020), BSR20200740.
[7]	W. Hu, C. Deng, Z. Ma, et al., Utilizing melatonin to combat bacterial infections and septic injury, Br. J. Pharmacol. 174 (2017) 754-768.
[8]	Q. Chen, T. Chen, W. Li, et al., Mycoepoxydiene inhibits lipopolysaccharide-induced inflammatory responses through the suppression of TRAF6 polyubiquitination [corrected, PLoS One 7 (2012), e44890.
[9]	Y. Lu, W.C. Yeh, and P.S. Ohashi, LPS/TLR4 signal transduction pathway, Cytokine 42 (2008) 145-151.
[10]	M. Tanaka, Y. Kishimoto, M. Sasaki, et al., Terminalia bellirica (gaertn.) roxb. extract and Gallic acid attenuate LPS-induced inflammation and oxidative stress via MAPK/NF-κB and akt/AMPK/Nrf2 pathways, Oxid. Med. Cell. Longev. 2018 (2018), 9364364.
[11]	W. Zhao, L. Ma, C. Cai, et al., Caffeine inhibits NLRP3 inflammasome activation by suppressing MAPK/NF-κB and A2aR signaling in LPS-induced THP-1 macrophages, Int. J. Biol. Sci. 15 (2019) 1571-1581.
[12]	J.E. Thompson, R.J. Phillips, H. Erdjument-Bromage, et al., I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B, Cell 80 (1995) 573-582.
[13]	L. Wang, X. Qiao, S. Zhang, et al., Porcine transmissible gastroenteritis virus nonstructural protein 2 contributes to inflammation via NF-κB activation, Virulence 9 (2018) 1685-1698.
[14]	J. Meng, H. Gao, W. Zhai, et al., Subtle regulation of cotton resistance to Verticillium wilt mediated by MAPKK family members, Plant Sci. 272 (2018) 235-242.
[15]	J. Bai, Y. Zhang, C. Tang, et al., Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases, Biomed. Pharmacother. 133 (2021), 110985.
[16]	S. Zhou, M. Chen, Y. Zhang, et al., OsMKK3, a stress-responsive protein kinase, positively regulates rice resistance to Nilaparvata lugens via phytohormone dynamics, Int. J. Mol. Sci. 20 (2019), 3023.
[17]	M. Jiang and Z. Chu, Comparative analysis of plant MKK gene family reveals novel expansion mechanism of the members and sheds new light on functional conservation, BMC Genomics 19 (2018), 407.
[18]	L. Ulloa and K.J. Tracey, The "cytokine profile": A code for sepsis, Trends Mol. Med. 11 (2005) 56-63.
[19]	Z. Chen, Pien Tze Huang (PZH) as a multifunction medicinal agent in traditional Chinese medicine (TCM): A review on cellular, molecular and physiological mechanisms, Cancer Cell Int. 21 (2021), 146.
[20]	H. Zheng, X. Wang, Y. Zhang, et al., Pien-Tze-Huang ameliorates hepatic fibrosis via suppressing NF-κB pathway and promoting HSC apoptosis, J. Ethnopharmacol. 244 (2019), 111856.
[21]	Y. Deng, H. Luo, J. Shu, et al., Pien Tze Huang alleviate the joint inflammation in collagen-induced arthritis mice, Chin. Med. 15 (2020), 30.
[22]	X. Qiu, Q. Guo, X. Liu, et al., Pien tze Huang alleviates relapsing-remitting experimental autoimmune encephalomyelitis mice by regulating Th1 and Th17 cells, Front. Pharmacol. 9 (2018), 1237.
[23]	Q. Chen, S. Zhuang, Y. Hong, et al., Demethylase JMJD2D induces PD-L1 expression to promote colorectal cancer immune escape by enhancing IFNGR1-STAT3-IRF1 signaling, Oncogene 41 (2022) 1421-1433.
[24]	T. Hu, Z. An, C. Shi, et al., A sensitive and efficient method for simultaneous profiling of bile acids and fatty acids by UPLC-MS/MS, J. Pharm. Biomed. Anal. 178 (2020), 112815.
[25]	T. Yang, T. Shu, G. Liu, et al., Quantitative profiling of 19 bile acids in rat plasma, liver, bile and different intestinal section contents to investigate bile acid homeostasis and the application of temporal variation of endogenous bile acids, J. Steroid Biochem. Mol. Biol. 172 (2017) 69-78.
[26]	P. Bhargava, M.D. Smith, L. Mische, et al., Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation, J. Clin. Invest. 130 (2020) 3467-3482.
[27]	X. Wang, X. Meng, J.R. Kuhlman, et al., Knockout of Mkp-1 enhances the host inflammatory responses to gram-positive bacteria, J. Immunol. 178 (2007) 5312-5320.
[28]	L. Li, Y. Liu, H.Z. Chen, et al., Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation, Nat. Chem. Biol. 11 (2015) 339-346.
[29]	] J.M. Cavaillon, Exotoxins and endotoxins: Inducers of inflammatory cytokines, Toxicon 149 (2018) 45-53.
[30]	R. Li, Y. Guo, Y. Zhang, et al., Salidroside ameliorates renal interstitial fibrosis by inhibiting the TLR4/NF-κB and MAPK signaling pathways, Int. J. Mol. Sci. 20 (2019), 1103.
[31]	D. Priem, G. van Loo, and M.J.M. Bertrand, A20 and cell death-driven inflammation, Trends Immunol. 41 (2020) 421-435.
[32]	X. Huang, Z. Feng, Y. Jiang, et al., VSIG4 mediates transcriptional inhibition of Nlrp3 and Il-1β in macrophages, Sci. Adv. 5 (2019), eaau7426.
[33]	O. Chavez-Talavera, A. Tailleux, P. Lefebvre, et al., Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease, Gastroenterology 152 (2017) 1679-1694.e3.
[34]	W. Jia, G. Xie, and W. Jia, Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis, Nat. Rev. Gastroenterol. Hepatol. 15 (2018) 111-128.
[35]	N.S. Nagathihalli, Y. Beesetty, W. Lee, et al., Novel mechanistic insights into ectodomain shedding of EGFR ligands amphiregulin and TGF-α: Impact on gastrointestinal cancers driven by secondary bile acids, Cancer Res. 74 (2014) 2062-2072.
[36]	H.S. Schadt, A. Wolf, J.A. Mahl, et al., Bile acid sequestration by cholestyramine mitigates FGFR4 inhibition-induced ALT elevation, Toxicol. Sci. 163 (2018) 265-278.
[37]	E. Ibrahim, I. Diakonov, D. Arunthavarajah, et al., Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: Role of Gi protein, muscarinic receptors and TGR5, Sci. Rep. 8 (2018), 7110.
[38]	J.E. Gotts and M.A. Matthay, Sepsis: Pathophysiology and clinical management, BMJ 353 (2016), i1585.
[39]	C.J. Fisher, Jr., J.M. Agosti, S.M. Opal, et al., Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein, N Engl J. Med. 334 (1996) 1697-1702.
[40]	V.S. Madamsetty, R. Mohammadinejad, I. Uzieliene, et al., Dexamethasone: Insights into pharmacological aspects, therapeutic mechanisms, and delivery systems, ACS Biomater. Sci. Eng. 8 (2022) 1763-1790.
[41]	T.F. Yeh, Y.J. Lin, W.S. Hsieh, et al., Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: A multicenter clinical trial, Pediatrics 100 (1997), E3.
[42]	T. Xia, M. Zhang, W. Lei, et al., Advances in the role of STAT3 in macrophage polarization, Front. Immunol. 14 (2023), 1160719.
[43]	M. Saraiva, P. Vieira, and A. O’Garra, Biology and therapeutic potential of interleukin-10, J. Exp. Med. 217 (2020), e20190418.
[44]	P. Comeglio, A. Morelli, L. Adorini, et al., Beneficial effects of bile acid receptor agonists in pulmonary disease models, Expert Opin. Investig. Drugs 26 (2017) 1215-1228.
[45]	Z. Cai, S. Yuan, Y. Zhong, et al., Amelioration of endothelial dysfunction in diabetes: Role of takeda G protein-coupled receptor 5, Front. Pharmacol. 12 (2021), 637051.