Monascin and Ankaflavin of Monascus purpureus Prevent Alcoholic Liver Disease through Regulating AMPK-Mediated Lipid Metabolism and Enhancing Both Anti-Inflammatory and Anti-Oxidative Systems

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.

Functional Teas from Penthorum chinense Pursh Alleviates Ethanol-Induced Hepatic Oxidative Stress and Autophagy Impairment in Zebrafish via Modulating the AMPK/p62/Nrf2/mTOR Signaling Axis

“…In addition, AMPK is an energy sensor that is an upstream molecule of autophagy (W. S. He, Wu, Ren, Yu, & Zhao, 2021). In the former publications, Monascin regulated AMPK-mediated ethanol-induced liver injury by regulating p62 and autophagy crosstalk with the Keap1 / Nrf2 pathway (Lai, Hsu, Pan, & Lee, 2021). Similarly, in our study, an increase of p-AMPK protein expression was observed by pretreatment with PCP, and then promoting p62-mediated autophagic degradation of Keap1.…”

1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation

“…Previous studies have confirmed and proved that ABL can reduce the inflammatory response induced by LPS by blocking the nuclear translocation of NF-κB p65 and inhibiting the phosphorylation and degradation of IκBα . Some data also suggest that alcohol exposure promotes the release of cytokines IL-1β and TNF-α . Therefore, it reduces alcohol-induced liver toxicity by preventing the production of IL-1β and TNF-α.…”

“… 36 Some data also suggest that alcohol exposure promotes the release of cytokines IL-1β and TNF-α. 37 Therefore, it reduces alcohol-induced liver toxicity by preventing the production of IL-1β and TNF-α. In our study, ABL significantly inhibited the increase of IL-1β and TNF-α caused by alcohol.…”

Increased Water-Soluble Yellow Monascus Pigment Productivity via Dual Mutagenesis and Submerged Repeated-Batch Fermentation of Monascus purpureus

“…Generally, MPs are red (RMPs, such as monascorubramine and rubropunctamine), orange (OMPs, such as rubropunctatin and monascorubrin), and yellow (YMPs, such as monascin and ankaflavin; Kim and Ku, 2018 ; Liu et al, 2019a ). It has been reported that YMPs are an excellent colorants and are safe, with anti-inflammatory, anti-fatty, antitumor, and antioxidant functions ( Wu et al, 2021 ; Huang et al, 2021b ), improving alcoholic liver injury and preventing lipid accumulation ( Zhou et al, 2019 ; Lai et al, 2021 ), with great prospects for use in food and pharmaceutical industries. However, YMPs are normally hydrophobic or alcohol-soluble intracellular pigments in submerged fermentation, increasing the cost of separation and purification, and limiting their application ( Gong and Wu, 2016 ; Yang et al, 2020 ).…”