Hepatoprotective Effect of Nakai Adventitious Roots Extract by Regulating CYP450 and PPAR Signaling Pathway

Overview

Journal Front Pharmacol

Date 2022 May 19

PMID 35586046

Authors

Xiao-Long Jiang

Pan-Yue Luo

Yan-Ying Zhou

Zhi-Hui Luo

Yue-Jun Hao

Ming-Zhi Fan

Xiao-Han Wu

Hao Gao

Hui-Chang Bi

Zhi-Bin Zhao

Mei-Lan Lian

Zhe-Xiong Lian

Affiliations

Soon will be listed here.

Abstract

Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of on liver protection. chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of and . This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism.

Citing Articles

Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.

Li S, Yin S, Ding H, Shao Y, Zhou S, Pu W Cell Prolif. 2022; 56(1):e13346.

PMID: 36229407 DOI: 10.1111/cpr.13346.

References

Shi C, Hao B, Yang Y, Muhammad I, Zhang Y, Chang Y . JNK Signaling Pathway Mediates Acetaminophen-Induced Hepatotoxicity Accompanied by Changes of Glutathione S-Transferase A1 Content and Expression. Front Pharmacol. 2019; 10:1092. PMC: 6763582. DOI: 10.3389/fphar.2019.01092. View

Ahmad S, Arjumand W, Nafees S, Seth A, Ali N, Rashid S . Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicol Lett. 2011; 208(2):149-61. DOI: 10.1016/j.toxlet.2011.10.023. View

Cao P, Sun J, Sullivan M, Huang X, Wang H, Zhang Y . Angelica sinensis polysaccharide protects against acetaminophen-induced acute liver injury and cell death by suppressing oxidative stress and hepatic apoptosis in vivo and in vitro. Int J Biol Macromol. 2018; 111:1133-1139. DOI: 10.1016/j.ijbiomac.2018.01.139. View

Martin-Murphy B, Holt M, Ju C . The role of damage associated molecular pattern molecules in acetaminophen-induced liver injury in mice. Toxicol Lett. 2009; 192(3):387-94. PMC: 2822049. DOI: 10.1016/j.toxlet.2009.11.016. View

Stephens C, Andrade R, Lucena M . Mechanisms of drug-induced liver injury. Curr Opin Allergy Clin Immunol. 2014; 14(4):286-92. DOI: 10.1097/ACI.0000000000000070. View

Wang J, Li P, Liu S, Zhang B, Hu Y, Ma H . Green tea leaf powder prevents dyslipidemia in high-fat diet-fed mice by modulating gut microbiota. Food Nutr Res. 2020; 64. PMC: 7681786. DOI: 10.29219/fnr.v64.3672. View

Williams C, Bajt M, Sharpe M, McGill M, Farhood A, Jaeschke H . Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans. Toxicol Appl Pharmacol. 2014; 275(2):122-33. PMC: 3941640. DOI: 10.1016/j.taap.2014.01.004. View

Liu Y, Wang J, Luo S, Zhan Y, Lu Q . The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review. J Autoimmun. 2020; 113:102510. PMC: 7327470. DOI: 10.1016/j.jaut.2020.102510. View

Lickteig A, Fisher C, Augustine L, Aleksunes L, Besselsen D, Slitt A . Efflux transporter expression and acetaminophen metabolite excretion are altered in rodent models of nonalcoholic fatty liver disease. Drug Metab Dispos. 2007; 35(10):1970-8. DOI: 10.1124/dmd.107.015107. View

10.

Liu K, Wang F, Xu R . Neutrophils in liver diseases: pathogenesis and therapeutic targets. Cell Mol Immunol. 2020; 18(1):38-44. PMC: 7852892. DOI: 10.1038/s41423-020-00560-0. View

11.

Jiang Y, Fan X, Wang Y, Tan H, Chen P, Zeng H . Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem Biol Interact. 2015; 231:83-9. DOI: 10.1016/j.cbi.2015.02.022. View

12.

Fan X, Chen P, Jiang Y, Wang Y, Tan H, Zeng H . Therapeutic efficacy of Wuzhi tablet (Schisandra sphenanthera Extract) on acetaminophen-induced hepatotoxicity through a mechanism distinct from N-acetylcysteine. Drug Metab Dispos. 2014; 43(3):317-24. PMC: 6067383. DOI: 10.1124/dmd.114.062067. View

13.

Cani P, de Vos W . Next-Generation Beneficial Microbes: The Case of . Front Microbiol. 2017; 8:1765. PMC: 5614963. DOI: 10.3389/fmicb.2017.01765. View

14.

Hanawa N, Shinohara M, Saberi B, Gaarde W, Han D, Kaplowitz N . Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury. J Biol Chem. 2008; 283(20):13565-77. PMC: 2376214. DOI: 10.1074/jbc.M708916200. View

15.

Bernal W, Wendon J . Acute liver failure. N Engl J Med. 2013; 369(26):2525-34. DOI: 10.1056/NEJMra1208937. View

16.

Jaeschke H, Williams C, Ramachandran A, Bajt M . Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 2011; 32(1):8-20. PMC: 3586825. DOI: 10.1111/j.1478-3231.2011.02501.x. View

17.

Du K, Ramachandran A, Jaeschke H . Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential. Redox Biol. 2016; 10:148-156. PMC: 5065645. DOI: 10.1016/j.redox.2016.10.001. View

18.

Zhao H, Jiang Z, Chang X, Xue H, Yahefu W, Zhang X . 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice. Front Pharmacol. 2018; 9:653. PMC: 6020787. DOI: 10.3389/fphar.2018.00653. View

19.

Gong S, Lan T, Zeng L, Luo H, Yang X, Li N . Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018; 69(1):51-59. PMC: 6365016. DOI: 10.1016/j.jhep.2018.02.024. View

20.

Bae H, Leung P, Hodge D, Fenimore J, Jeon S, Thovarai V . Multi-omics: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases. J Autoimmun. 2020; 111:102436. PMC: 7266723. DOI: 10.1016/j.jaut.2020.102436. View