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Hepatoprotective Effect of Loquat Leaf Flavonoids in PM2.5-Induced Non-Alcoholic Fatty Liver Disease via Regulation of IRs-1/Akt and CYP2E1/JNK Pathways

1
Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
2
College of Forest, Nanjing Forestry University, Nanjing 210037, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3005; https://doi.org/10.3390/ijms19103005
Received: 29 August 2018 / Revised: 23 September 2018 / Accepted: 26 September 2018 / Published: 1 October 2018
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Abstract

Ambient air particulate matter (PM) represents a class of heterogeneous substances present in polluted air, which contains many harmful components. Exposure to ambient particulate matter in fine rages (PM2.5) is associated with non-alcoholic fatty liver disease (NAFLD). Loquat Leaf possesses pharmacological actions on NAFLD. As the main biological active ingredients, the potential therapeutic role of total flavonoids (TF) isolated from Loquat Leaf in PM2.5-induced NAFLD model remains unclear. The present study was designed to explore the hepatoprotective effect of TF in PM2.5-induced NAFLD mice with its related mechanisms of action. Mice were exposed to PM2.5 to induce NAFLD, and body weight, the ratio of liver to body weight, and blood lipids increased significantly compared with the control group. It was found that TF significantly reduced the above parameters in PM2.5-induced NAFLD mice. TF treatment alleviated oxidative stress by preventing the accumulation of oxidative product malondialdehyde (MDA) and by strengthening the anti-oxidative capacity of superoxide dismutase (SOD). TF was also found to reduce the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the PM2.5 group. In addition, TF repaired the PM2.5-induced decline of insulin receptor substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. Meanwhile, the data showed TF suppressed the expression of cytochrome P450 2E1(CYP2E1) and the phosphorylation of c-jun N-terminal kinase (JNK) in PM2.5-induced NAFLD. Taken together, these findings show that TF alleviate PM2.5-induced NAFLD via regulation of IRs-1/Akt and CYP2E1/JNK pathways, which may have potential for further development as novel therapeutic agents for NAFLD. View Full-Text
Keywords: PM2.5; Loquat Leaf; total flavonoids; non-alcoholic fatty liver disease; insulin resistance; oxidative stress; IRs/Akt; CYP2E1/JNK PM2.5; Loquat Leaf; total flavonoids; non-alcoholic fatty liver disease; insulin resistance; oxidative stress; IRs/Akt; CYP2E1/JNK
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Jian, T.; Ding, X.; Wu, Y.; Ren, B.; Li, W.; Lv, H.; Chen, J. Hepatoprotective Effect of Loquat Leaf Flavonoids in PM2.5-Induced Non-Alcoholic Fatty Liver Disease via Regulation of IRs-1/Akt and CYP2E1/JNK Pathways. Int. J. Mol. Sci. 2018, 19, 3005.

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