Login Register Cart 0
Research Article

Gentianella turkestaum通过调节内质网应激和NF-κB信号通路显示对肝损伤的保护作用

卷 19, 期 6, 2019

页: [452 - 460] 页: 9

弟呕挨: 10.2174/1566524019666190415124838

价格: $65

conference banner
摘要

目的：研究丁醇（指定为GBA）对Gentianella turkestaumum提取物对四氯化碳（CCl4）和过氧化氢（H2O2）诱导的肝细胞L02损伤的保护作用。 方法：将L02细胞与5μg/ mL，10μg/ mL，20μg/ mL，40μg/ mL，60μg/ mL，80μg/ mL和100μg/ mL GBA孵育24小时，然后进行MTT分析用于筛选GBA的细胞毒性。将细胞分为空白对照组，CCl4 / H2O2模型组，CCl4（20 mmol / L）或H2O2（100μmol/ L）处理;水飞蓟素+ CCl4 / H2O2组，CCl4（20 mmol / L）或H2O2（100μmol/ L）和5μg/ mL水飞蓟素处理; GBA + CCl4 / H2O2组，用CCl4（20mmol / L）或H2O2（100μmol/ L）和GBA（5μg/ mL，10μg/ mL和20μg/ mL）处理。进行MTT测定以确定细胞活性。使用商业试剂盒测定丙二醛（MDA）含量。测定上清液中的丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST）。采用PE-Annexin V / 7-ADD方法测定细胞凋亡。 RT-PCR用于评估内质网应激相关基因（CHOP，PERK，IRE1和ATF6）mRNA的表达。进行Western印迹分析以确定CHOP，Caspase 12和NF-κB蛋白的表达。 结果：GBA（5μg/ mL，10μg/ mL和20μg/ mL）孵育后的细胞存活率≥75％。 GBA孵育后，ALT和AST水平显着下降（P <0.05），而MDA水平显着下降（P <0.05）。与对照组相比，CCl4或H2O2组的细胞凋亡显着增加（P <0.05）。相比之下，与CCl4或H2O2组相比，GBA预孵育可以减弱细胞凋亡，其呈剂量依赖性方式（P <0.05）。在CCl4或H2O2存在下，CHOP，PERK，IRE1和ATF6 mRNA的表达显着上调（P <0.05）。然而，GBA此后诱导这些mRNA显着减少（P <0.05），同时CHOP和Caspase 12蛋白减少（P <0.05）。此外，它可以减弱核蛋白中NF-κBp65的表达。 结论：G。turkestanerum可抑制脂质过氧化，提高抗氧化活性。此外，它可以通过下调ERS相关基因和蛋白质的转录水平来抑制细胞凋亡。该过程与NF-κBp65蛋白的核转位相关。

关键词: Gentianella turkestanerum，肝脏L02细胞，肝损伤，四氯化碳，过氧化氢，丁醇。

« 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.

Rights & Permissions Print Cite
Article Metrics
48
3
1
© 2024 Bentham Science Publishers | Privacy Policy