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

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.

Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

“…Flavonoids product has numerous biological properties, which may be promising therapeutic agents for NASH (Li and Schluesener, 2017). Many natural products are rich in flavonoids and possess anti-oxidative and anti-inflammatory activities against NASH (Jian et al, 2018;Parafati et al, 2018;Wang et al, 2018). Various flavonoid compounds have been identified, such as flavones, flavanones, flavanols, flavonols, and chalcones (Rzepecka-Stojko et al, 2015).…”

Toxicity of Zirconia oxide Nanoparticles: Liver Biodistribution and Liver Damages

“…Downregulation of Igfbp2 was reported to be the maker of NAFLD [38]. As a symptom of metabolic disorders, hepatic lipid accumulation is strongly associated with insulin resistance [39]. Insulin resistance, which is characteristic of IRs/Akt depression, has been recognized for many years to be an essential component of NAFLD A recent study investigated the toxicol profiles of several metal oxide NPs (including some rare earth oxides and transition metal oxides) in hepatocytes and proved that they could induce hepatocyte death by apoptosis [36].…”

CRISPR/Cas9-Mediated Whole Genomic Wide Knockout Screening Identifies Specific Genes Related to Mineral Absorption Involving in PM2.5 Liver Toxicity

“…Although there are some mechanisms of PM 2.5 induced liver deceases are reported, such as in ammatory, ROS and FXR, they focus on studying the physiological changes and molecular pathways in the body after PM 2.5 exposure [9,11,26]. As Qingzhao Li ,etc.…”