Hepatotoxic Components Effect of and Associated Molecular Mechanism by Integrated Transcriptome and Molecular Docking

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Apr 28

PMID 37110661

Authors

Liwen Ai

Fan Yang

Wanjun Hu

Liyang Guo

Weixue Liu

Xuexue Xue

Lulu Li

Zunlai Sheng

Affiliations

Soon will be listed here.

Abstract

(CF) is a natural medicinal plant widely used for its various pharmacological properties. Natural products used to cure several diseases have been considered safe thanks to their little or no side effects. However, in recent years, a hepatotoxic effect has been found due to the abuse of herbal medicine. CF has been reported to have hepatotoxicity, but the mechanism is unclear. In this experiment, the toxic aspect and mechanism of CF action were evaluated by transcriptome analysis. Components of toxic CF fractions were identified by LC-MS, and hepatotoxic toxic components in toxic CF fractions were predicted by molecular docking. The results showed that the ethyl acetate part of CF was the main toxic fraction, and transcriptome analysis found that the toxic mechanism was highly related to lipid metabolism-related pathways, and CFEA could inhibit the PPAR signaling pathway. Molecular docking results showed that 3'--methyl-4--(n″--galloyl-β-d-xylopyranosyl) ellagic acid ( = 2, 3 or 4) and 4--(3″,4″--digalloyl-α-l-rhamnosyl) ellagic acid have better docking energies with PPARα protein and FABP protein than other components. In summary, 3'--methyl-4--(n″--galloyl-β-d-xylopyranosyl) ellagic acid ( = 2, 3 or 4) and 4--(3″,4″--digalloyl-α-l-rhamnosyl) ellagic acid were the main toxic components, which may play a toxic role by inhibiting the PPAR signaling pathway and affect lipid metabolism.

Citing Articles

Integrated virtual screening and studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel.

Song L, Mi S, Zhao Y, Liu Z, Wang J, Wang H Front Pharmacol. 2024; 15:1367682.

PMID: 38500766 PMC: 10945000. DOI: 10.3389/fphar.2024.1367682.

References

McCabe M, Waters S, Morris D, Kenny D, Lynn D, Creevey C . RNA-seq analysis of differential gene expression in liver from lactating dairy cows divergent in negative energy balance. BMC Genomics. 2012; 13:193. PMC: 3465249. DOI: 10.1186/1471-2164-13-193. View

Wu Z, Ding L, Bao J, Liu Y, Zhang Q, Wang J . Co-infection of and Triggers Inflammatory Injury Involving the IL-17 Signaling Pathway. Front Microbiol. 2019; 10:2615. PMC: 6872679. DOI: 10.3389/fmicb.2019.02615. View

Xie C, Mao X, Huang J, Ding Y, Wu J, Dong S . KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res. 2011; 39(Web Server issue):W316-22. PMC: 3125809. DOI: 10.1093/nar/gkr483. View

Li N, Li B, Zhang J, Liu X, Liu J, Li K . Protective effect of phenolic acids from Chebulae Fructus immaturus on carbon tetrachloride induced acute liver injury via suppressing oxidative stress, inflammation and apoptosis in mouse. Nat Prod Res. 2019; 34(22):3249-3252. DOI: 10.1080/14786419.2018.1553174. View

Arseculeratne S, Gunatilaka A, PANABOKKE R . Studies of medicinal plants of Sri Lanka. Part 14: Toxicity of some traditional medicinal herbs. J Ethnopharmacol. 1985; 13(3):323-35. DOI: 10.1016/0378-8741(85)90078-9. View

Hamza A, Ahmed M, Elwey H, Amin A . Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats and Potentiates Its Anticancer Activity on MCF-7 Cells. PLoS One. 2016; 11(11):e0167049. PMC: 5120835. DOI: 10.1371/journal.pone.0167049. View

Touhidul Islam S, Won J, Khan M, Chavin K, Singh I . Peroxisomal footprint in the pathogenesis of nonalcoholic steatohepatitis. Ann Hepatol. 2019; 19(5):466-471. DOI: 10.1016/j.aohep.2019.11.007. View

Avula B, Wang Y, Wang M, Shen Y, Khan I . Simultaneous determination and characterization of tannins and triterpene saponins from the fruits of various species of Terminalia and Phyllantus emblica using a UHPLC-UV-MS method: application to triphala. Planta Med. 2013; 79(2):181-8. DOI: 10.1055/s-0032-1328089. View

Zhang Y, Jiang Z, Su Y, Chen M, Li F, Liu L . Gene expression profiling reveals potential key pathways involved in pyrazinamide-mediated hepatotoxicity in Wistar rats. J Appl Toxicol. 2012; 33(8):807-19. DOI: 10.1002/jat.2736. View

10.

Ekambaram S, Babu K, Perumal S, Rajendran D . Repeated oral dose toxicity study on hydrolysable tannin rich fraction isolated from fruit pericarps of Terminalia chebula Retz in Wistar albino rats. Regul Toxicol Pharmacol. 2017; 92:182-188. DOI: 10.1016/j.yrtph.2017.12.001. View

11.

Miller W, Auchus R . The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2010; 32(1):81-151. PMC: 3365799. DOI: 10.1210/er.2010-0013. View

12.

Wu Z, Chen C, Miao Y, Liu Y, Zhang Q, Li R . Baicalin Attenuates -Induced Inflammation via Inhibition of the TLR2-NF-κB Pathway in Chicken and DF-1 Cells. Infect Drug Resist. 2020; 12:3911-3923. PMC: 6929927. DOI: 10.2147/IDR.S231908. View

13.

Tasduq S, Singh K, Satti N, Gupta D, Suri K, Johri R . Terminalia chebula (fruit) prevents liver toxicity caused by sub-chronic administration of rifampicin, isoniazid and pyrazinamide in combination. Hum Exp Toxicol. 2006; 25(3):111-8. DOI: 10.1191/0960327106ht601oa. View

14.

Shi Z, Zhu J, Guo Y, Niu M, Zhang L, Tu C . Epigallocatechin Gallate During Dietary Restriction - Potential Mechanisms of Enhanced Liver Injury. Front Pharmacol. 2021; 11:609378. PMC: 7878556. DOI: 10.3389/fphar.2020.609378. View

15.

Chen L, Chen X, Huang X, Song B, Wang Y, Wang Y . Regulation of glucose and lipid metabolism in health and disease. Sci China Life Sci. 2019; 62(11):1420-1458. DOI: 10.1007/s11427-019-1563-3. View

16.

Leone T, Weinheimer C, Kelly D . A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci U S A. 1999; 96(13):7473-8. PMC: 22110. DOI: 10.1073/pnas.96.13.7473. View

17.

Pfundstein B, El Desouky S, Hull W, Haubner R, Erben G, Owen R . Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): characterization, quantitation and determination of antioxidant capacities. Phytochemistry. 2010; 71(10):1132-48. DOI: 10.1016/j.phytochem.2010.03.018. View

18.

Henry Z, Argo C . How to Identify the Patient with Nonalcoholic Steatohepatitis Who Will Progress to Cirrhosis. Gastroenterol Clin North Am. 2020; 49(1):45-62. DOI: 10.1016/j.gtc.2019.09.002. View

19.

Wang X, Li F, Liu J, Ji C, Wu H . Transcriptomic, proteomic and metabolomic profiling unravel the mechanisms of hepatotoxicity pathway induced by triphenyl phosphate (TPP). Ecotoxicol Environ Saf. 2020; 205:111126. DOI: 10.1016/j.ecoenv.2020.111126. View

20.

Ahmadi-Naji R, Heidarian E, Ghatreh-Samani K . Evaluation of the effects of the hydroalcoholic extract of fruits on diazinon-induced liver toxicity and oxidative stress in rats. Avicenna J Phytomed. 2017; 7(5):454-466. PMC: 5641420. View