Quercetin prevents cadmium chloride‐induced hepatic steatosis and fibrosis by downregulating the transcription ofmiR‐21

Abstract

This study investigated if cadmium chloride (CdCl 2 )-induced hepatic steatosis and fibrosis and the protective effect of quercetin (QUR) are mediated modulating the activity of miR-21, a known hepatic lipogenic and fibrotic miRNA. Male rats (n = 8/group) were divided as control, control + QUR (50 mg/kg; orally), CdCl 2 (10 moml/L; drinking water), CdCl 2 + miR-21 antagomir (inhibitor) (16 mg/kg/first 3 days), and CdCl 2 + QUR (50 mg/kg). Treatments were conducted for 20 weeks, daily. All treatments showed no effect on fasting glucose and insulin levels. Administration of either miR-21 or QUR prevented CdCl 2 -induced hepatic damage, as well as lipid droplets and collagen deposition. They also reduced serum levels of ALT and AST and decreased serum and hepatic levels of total cholesterol, triglycerides, and low-density lipoproteins in CdCl 2 -treated rats. Concomitantly, they reduced hepatic levels of reactive oxygen species, malondialdehyde, interleukin-6, and tumor necrosis factor-α, suppressed the activation of NF-kb P65, and increased hepatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), and superoxide dismutase (SOD). These effects were associated with reduced expression of SREBP1, TGF-β1, Smad3, and collagen1 A and increased expression of PPARα, CPT1, and smad7. Interestingly, QUR significantly lowered levels of miR-21 and increased the protein levels and activity of Nrf2, as well as levels of GSH and SOD in the livers of both the control and CdCl 2 -treated rats. Of note, levels of Nrf2 were negatively correlated with the transcription of miR-21. In conclusion: QUR prevents CdCl 2 -induced hepatic steatosis and fibrosis mainly through attenuating its ability to upregulate miR-21, at least, by upregulation of Nrf2.

Traditional Chinese Medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives

“…Another component, quercetin can not only eliminate lipid droplets but also restore the upregulated total cholesterol and triglyceride levels in HepG2 cells co-cultured with high D-glucose and free fatty acid [ 36 ]. In rodent model, quercetin can prevent CdCl 2 -induced hepatic steatosis and fibrosis that through upregulating nuclear factor erythroid 2-related factor 2 [ 37 ]. Besides that, quercetin can revert gut microbiota imbalance and TLR-4 pathway induction mediated by endotoxemia, and then subsequently inhibit inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid metabolism and gene expression deregulation, which helps to alleviate NAFLD in HFD mice [ 38 ].…”

Influence of the Bioactive Diet Components on the Gene Expression Regulation

“…↑ miR-29b quercetin diabetic retinopathy [119] ↑ miR-146a breast cancer [120] ↓ miR-206 osteoporosis [121] ↓ miR-21 breast cancer [122] ↓ miR-22 oral lichen planus [123] ↓ miR-216a peripheral arterial disease [124] ↓ miR-21 hepatic steatosis and fibrosis [125] ↓ miR-15a and miR-16 hepatocellular carcinoma [126] ↓ miR-16 oral cancer [127] ↑ hsa-miR-24, hsa-miR-6769b-3p, hsa-miR-6836-3p, hsa-miR-199a-3p, hsa-miR-663a, hsa-miR-4739, hsa-miR-6892-3p, hsa-miR-7107-5p, hsa-miR-1273g-3p, hsa-miR-1343, and hsa-miR-6089; ↓ hsa-miR-181a-5p…”

Quercetin ameliorates thioacetamide‐induced hepatic fibrosis and oxidative stress by antagonizing the Hedgehog signaling pathway

“…Quercetin treated group received intraperitoneal injections of thioacetamide twice a week for 6 weeks, followed by oral intake of quercetin (50 mg/kg) daily for 4 weeks. 22 While silymarin treated group received intraperitoneal injection of thioacetamide twice a week for 6 weeks followed by oral intake of silymarin (50 mg/kg) daily for 4 weeks. 23 Rats were killed at the end of the experiment, blood was drawn from the cardiac puncture, and the liver was removed and stored for gene expression analysis and histopathological changes.…”