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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Gentianella turkestanerum Showed Protective Effects on Hepatic Injury by Modulating the Endoplasmic Reticulum Stress and NF-κB Signaling Pathway

Author(s): Jianhua Yang, Dandan Zhu, Limei Wen, Xueying Xiang and Junping Hu*

Volume 19, Issue 6, 2019

Page: [452 - 460] Pages: 9

DOI: 10.2174/1566524019666190415124838

Price: $65

Abstract

Objective: To investigate the protective effects of Gentianella turkestanerum extraction by butanol (designated as GBA) on hepatic cell line L02 injury induced by carbon tetrachloride (CCl4) and hydrogen peroxide (H2O2).

Methods: L02 cells were incubated with 5 µg/mL, 10 µg/mL, 20 µg/mL, 40 µg/mL, 60 µg/mL, 80 µg/mL and 100 µg/mL GBA for 24 hours, and then MTT assay was used to screen the cytotoxicity for GBA. Cells were divided into blank control group, CCl4/H2O2 model group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L); silymarin+CCl4/H2O2 group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L) and 5 µg/mL silymarin; GBA+CCl4/H2O2 group, treated by CCl4 (20 mmol/L) or H2O2 (100 µmol/L) and GBA (5 µg/mL, 10 µg/mL and 20 µg/mL). MTT assay was performed to determine the cellular activity. Malondialdehyde (MDA) content was determined using a commercial kit. The alanine transaminase (ALT), aspartate transaminase (AST) in the supernatant was determined. PE-Annexin V/7-ADD method was utilized to determine the apoptosis of cells. RT-PCR was used to evaluate the expression of endoplasmic reticulum stressrelated genes (CHOP, PERK, IRE1 and ATF6) mRNA. Western blot analysis was performed to determine the expression of CHOP, Caspase 12 and NF-κB protein.

Results: Cellular survival after GBA (5 µg/mL, 10 µg/mL and 20 µg/mL) incubation was ≥ 75%. After GBA incubation, levels of ALT and AST showed a significant decrease (P < 0.05), while that of the MDA showed a significant decrease (P < 0.05). The apoptosis in the CCl4 or H2O2 group showed a significant increase compared to the control group (P < 0.05). In contrast, GBA-preincubation could attenuate the cellular apoptosis compared to the CCl4 or H2O2 group, which displayed a dose-dependent manner (P < 0.05). The expression of CHOP, PERK, IRE1 and ATF6 mRNA was significantly up-regulated in the presence of CCl4 or H2O2 (P < 0.05). Whereas, GBA induced a significant decrease in these mRNA thereafter (P < 0.05), together with a decrease in CHOP and Caspase 12 proteins (P < 0.05). Besides, it could attenuate the expression of NF-κB p65 in nuclear protein.

Conclusion: G. turkestanerum could inhibit the lipid peroxidation and increase the antioxidant activity. Also, it could inhibit the cellular apoptosis through down-regulating the transcriptional level of ERS related genes and proteins. This process was associated with the nuclear translocation of NF-κB p65 protein.

Keywords: Gentianella turkestanerum, Hepatic L02 cell, liver injury, carbon tetrachloride, hydrogen peroxide, butanol.

« Previous
[1]
Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol 2013; 3: 977-1010.
[2]
Luedde T, Kaplowitz N, Schwabe RF. Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology 2014; 147: 765-83.e764.
[3]
Angulo P, Machado MV, Diehl AM. Fibrosis in nonalcoholic Fatty liver disease: Mechanisms and clinical implications. Semin Liver Dis 2015; 35: 132-45.
[4]
Zhu P, Xue J, Zhang ZJ, et al. Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway. Cell Death Dis 2017; 8: 3207.
[5]
Zhang R, Piao MJ, Kim KC, et al. Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis. Int J Biochem Cell Biol 2012; 44: 224-32.
[6]
Liu MQ, Chen Z, Chen LX. Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases. Acta Pharmacol Sin 2016; 37: 425-43.
[7]
Liu Y, Wang J, Qi SY, et al. Reduced endoplasmic reticulum stress might alter the course of heart failure via caspase-12 and JNK pathways. Can J Cardiol 2014; 30: 368-75.
[8]
De Minicis S, Candelaresi C, Agostinelli L, et al. Endoplasmic Reticulum stress induces hepatic stellate cell apoptosis and contributes to fibrosis resolution. Liver Int 2012; 32: 1574-84.
[9]
Campos G. SchmidtHeck W, Ghallab A, et al.The transcription factor CHOP, a central component of the transcriptional regulatory network induced upon CCl4 intoxication in mouse liver, is not a critical mediator of hepatotoxicity. Arch Toxicol 2014; 88: 1267-80.
[10]
Huang YJ, Lu H, Yu XL, et al. Anti-inflammatory secoiridoid glycosides from Gentianella azurea. Bioorg Med Chem Lett 2014; 24: 5260-4.
[11]
Xu WJ, Li RJ, Quasie O, Yang MH, Kong LY, Luo J. Polyprenylated tetraoxygenated xanthones from the roots of hypericum monogynum and their neuroprotective activities. J Nat Prod 2016; 79: 1971-81.
[12]
Ito T, Fujimoto S, Suito F, Shimosaka M, Taguchi G. C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants. Plant J 2017; 91: 187-98.
[13]
Yang J, Zhu D, Ju B, Jiang X, Hu J. Hepatoprotective effects of Gentianella turkestanerum extracts on acute liver injury induced by carbon tetrachloride in mice. Am J Transl Res 2017; 9: 569-79.
[14]
Brea R, Motino O, Frances D, et al. PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p. Biochim Biophys Acta 2018; 1864: 325-37.
[15]
Cao XY, Wang ZZ. Simultaneous determination of four iridoid and secoiridoid glycosides and comparative analysis of Radix Gentianae Macrophyllae and their related substitutes by HPLC. Phytochem Anal 2010; 21: 348-54.
[16]
Mustafa AM, Caprioli G, Ricciutelli M, et al. Comparative HPLC/ESI-MS and HPLC/DAD study of different populations of cultivated, wild and commercial Gentiana lutea L. Food Chem 2015; 174: 426-33.
[17]
Kim SY, Kyaw YY, Cheong J. Functional interaction of endoplasmic reticulum stress and hepatitis B virus in the pathogenesis of liver diseases. World J Gastroenterol 2017; 23: 7657-65.
[18]
Zhou D, Ruan J, Cai Y, Xiong Z, Fu W, Wei A. Antioxidant and hepatoprotective activity of ethanol extract of Arachniodes exilis (Hance) Ching. J Ethnopharmacol 2010; 129: 232-7.
[19]
Huang Q, Zhang S, Zheng L, He M, Huang R, Lin X. Hepatoprotective effects of total saponins isolated from Taraphochlamys affinis against carbon tetrachloride induced liver injury in rats. Food Chem Toxicol 2012; 50: 713-8.
[20]
Dara L, Ji C, Kaplowitz N. The contribution of endoplasmic reticulum stress to liver diseases. Hepatology 2011; 53: 1752-63.
[21]
Xie Q, Khaoustov VI, Chung CC, et al. Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation. Hepatology 2002; 36: 592-601.
[22]
Thayumanavan P, Loganathan C, Iruthayaraj A, Poomani K, Nallaiyan S. S-allyl-glutathione, a synthetic analogue of glutathione protected liver against carbon tetrachloride toxicity: Focus towards anti-oxidative efficiency. Environ Toxicol Pharmacol 2017; 58: 21-8.
[23]
Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev 2012; 70: 257-65.
[24]
Yue S, Hu B, Wang Z, et al. Salvia miltiorrhiza compounds protect the liver from acute injury by regulation of p38 and NFkappaB signaling in Kupffer cells. Pharm Biol 2014; 52: 1278-85.
[25]
Li C, Yi LT, Geng D, Han YY, Weng LJ. Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice. Pharm Biol 2015; 53: 767-72.
[26]
Guicciardi ME, Gores GJ. Apoptosis: A mechanism of acute and chronic liver injury. Gut 2005; 54: 1024-33.
[27]
Kedia S, Sharma R, Makharia GK, et al. Imaging of the small intestine in Crohn’s disease: Joint position statement of the Indian Society of Gastroenterology and Indian Radiological and Imaging Association. Indian J Gastroenterol 2017; 36: 487-508.
[28]
Son G, Iimuro Y, Seki E, Hirano T, Kaneda Y, Fujimoto J. Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CCl4-induced liver injury and fibrosis. Am J Physiol Gastrointest Liver Physiol 2007; 293: G631-9.

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