Purpose: miR-122 is upregulated in non-alcoholic fatty liver disease (NAFLD) liver tissue, and knockdown of miR-122 protects hepatocytes from lipid metabolism disorders. This study aimed to investigate whether Huazhi Rougan Granule (HRG) alleviates NAFLD liver and intestinal injury by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway.

Methods: Rats with NAFLD were constructed by high-fat feeding. Serum levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using a fully automated biochemical instrument. Histopathological changes in the liver and small intestine were observed by HE staining. QRT-PCR detected the expression level of miR-122 in the liver tissues. The protein expression of TLR4, MyD88, NF- κB p65, and p-p65 in liver tissues was detected by western blotting.

Results: HRG slowed down the weight gain of NAFLD rats, decreased (P<0.05) the levels of TC, TG, ALT, AST, TNF-α, IL-1β, IL-6, LPS, and Hpt, improved the pathological status of liver and small intestine tissues, upregulated (P<0.05) the expression of ZO-1 and Occludin, downregulated (P<0.05) the protein expression of TLR4, MyD88, and p-p65, and inhibited (P<0.05) the expression of miR-122.

Conclusion: HRG may alleviate hepatic and intestinal injuries in rats with NAFLD by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway.

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http://dx.doi.org/10.2174/0113862073290372240603090844DOI Listing

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Purpose: miR-122 is upregulated in non-alcoholic fatty liver disease (NAFLD) liver tissue, and knockdown of miR-122 protects hepatocytes from lipid metabolism disorders. This study aimed to investigate whether Huazhi Rougan Granule (HRG) alleviates NAFLD liver and intestinal injury by regulating the miR-122-mediated TLR4/MyD88/NF-κB pathway.

Methods: Rats with NAFLD were constructed by high-fat feeding.

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Article Synopsis
  • - Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition in China linked to insulin resistance and genetics, prompting an analysis of traditional Chinese medicines alongside Western treatments to determine their effectiveness in improving liver health.
  • - The study included 77 randomized controlled trials with 7770 patients, focusing on clinical efficacy rates and blood lipid levels as primary outcomes, using various statistical tools for analysis.
  • - Results showed that Huazhi Rougan granules combined with Western medications had the highest efficacy rate (81.7%) and significantly improved blood lipids, while Danning tablets were most effective when used alone, demonstrating high clinical efficacy as well.
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To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway.

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Huazhi-Rougan (HZRG) formula is a Traditional Chinese medicine prescription, and has been widely used to treat non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and the underlying mechanisms of HZRG have not yet been characterized. Here we showed that 4-week HZRG treatment alleviated methionine-choline-deficiency (MCD) diet-induced NASH in C57BL/6J mice, as evidenced by the improvement of hepatic steatosis and inflammation, as well as the decrease of serum levels of alanine and aspartate transaminases.

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