Abstract
Background: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.
Highlights
Nonalcoholic fatty liver disease (NAFLD) disorders range from simple fatty liver to nonalcoholic steatohepatitis (NASH) and fibrosis/cirrhosis, which have been reported in a recent study [1]
We used Advanced glycation end products (AGEs) to induce the hepatic stellate cells (HSCs)-t6 cells activation, and we found that aqueous extracts from Solanum nigrum (AESN) (10 μM) treatment could inhibit the enhanced matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) expression caused by AGEs (Figure 1)
We found that AESN inhibited AGEs-induced HSCs activation and the expression of hepatic fibrogenetic biomarkers, including MMP-2 and α-SMA, independent of receptor for AGE (RAGE)
Summary
Nonalcoholic fatty liver disease (NAFLD) disorders range from simple fatty liver (steatosis without liver injury) to nonalcoholic steatohepatitis (NASH) and fibrosis/cirrhosis, which have been reported in a recent study [1]. We firstly induced hyperlipidemia and hyperglycemia for NASH development, and subsequently induced hepatic fibrosis by ethanol administration as an animal model for evaluation of Solanum nigrum against liver damage by blocking “two-hit theory”. Hyperglycemia and hyperlipidemia are common causes of chronic liver disease, which is strongly associated with insulin resistance, leading to NASH and hepatic fibrosis [3,4,5]. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease
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