Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis.

Vyacheslav Buko,Aliaksei Bakunovich,Dorota Żyżelewicz,Grażyna Budryn,Valentina Moroz,Viktor Rusin,Agnieszka Zakrzeska,Siarhei Kirko,Elena Belonovskaya,Małgorzata Zakłos-Szyda,Ilya Zavodnik

doi:10.3390/nu13114155

Abstract

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.

Highlights

Alcoholic liver disease (ALD) is a major component of morbidity and mortality in the world
The liver/body mass ratio was markedly elevated in ethanol-treated rats, and it decreased after the administration of both doses of chlorogenic acid (CGA) (Table 2)
In the current ratsinfed on the high-fat diet (HFD) were exposed alcoholresembling intoxicationthat for an an extended periodstudy, of time order to induce chronic liverto damage of extended period of time in order to induce chronic liver damage resembling that of chronic ALD in humans

Summary

Introduction

Alcoholic liver disease (ALD) is a major component of morbidity and mortality in the world. Excessive alcohol intake is the leading cause of ALD, which can progress from fatty liver (steatosis) to steatosis combined with inflammation (steatohepatitis) and further to cirrhosis and end-stage hepatocellular carcinoma. Over recent years, increasing attention has been paid to phytocompounds as promising therapeutic agents in the treatment of ALD. Several plant-derived substances, e.g., silymarin [2] and curcumin [3], have been previously shown to be quite effective in the treatment of ALD. Some other herbal substances, such as resveratrol [4], genistein, puerarin, and betulin [5], are promising medicines for the correction of alcohol-dependent liver pathology

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Conclusion