Abstract
Alcohol metabolism causes an excessive accumulation of liver lipids and inflammation, resulting in liver damage. The yellow pigments monascin (MS) and ankaflavin (AK) of Monascus purpureus-fermented rice were proven to regulate ethanol-induced damage in HepG2 cells, but the complete anti-inflammatory and anti-fatty liver mechanisms in the animal model are still unclear. This study explored the roles of MS and AK in improving alcoholic liver injury. MS and AK were simultaneously fed to evaluate their effects and mechanisms in C57BL/6J mice fed the Lieber–DeCarli liquid alcohol diet for 6 weeks. The results indicated that MS and AK significantly reduced the serum aspartate aminotransferase and alanine aminotransferase activity, as well as the total liver cholesterol and triglyceride levels. The histopathological results indicated that MS and AK prevented lipid accumulation in the liver. MS and AK effectively enhanced the activity of antioxidant enzymes and reduced the degree of lipid peroxidation; AK was particularly effective and exhibited a superior preventive effect against alcoholic liver injury and fatty liver. In addition to inhibiting the phosphorylation of the MAPK family, MS and AK directly reduced TNF-α, IL-6, and IL-1β levels, thereby reducing NF-κB and its downstream iNOS and COX-2 expressions, as well as increasing PPAR-γ, Nrf-2, and HO-1 expressions to prevent liver damage. MS and AK also directly reduced TNF-α, IL-6, and IL-1β expression, thereby reducing the production of NF-κB and its downstream iNOS and COX-2, and increasing PPAR-γ, Nrf-2, and HO-1 expressions, preventing alcohol damage to the liver.
Highlights
The initial stage of liver disease is liver damage
These results indicate that the test substances reduced the content of total cholesterol (TC) and TG, inhibited the lipid synthesis induced by alcohol, and reduced the accumulation of lipids in the liver
High doses of MS and AK further elevated the expression of PPAR-γ (p < 0.001). These results prove that MS and AK prevented the production of inflammatory factors by increasing PPAR-γ, reducing the inflammation caused by alcohol
Summary
The initial stage of liver disease is liver damage. Chronic liver damage can lead to fibrosis, liver failure, and liver cancer [1]. The reported effects of Monascus purpureus-fermented rice (red mold rice) include enhancing the activity of antioxidant en of zymes in the liver of mice, inhibiting the expression of inflammation-related factors, and reducing the damage caused by alcohol to liver cells [8]. Regarding alcoholic tional compounds for the prevention of cardiovascular disease, fatty liver, and lipogenesis liver disease, MS and AK were proven to regulate ethanol-induced peroxisome prolifera(Figure 1) [9,10,11]. Both MS and AK can achieve anti-inflammatory effects by tor-activated receptor-γ and sterol regulatory element-binding transcription factor-1 exreducing inflammatory factor levels [12,13].
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