Polygala fallax Hemsl polysaccharides alleviated alcoholic fatty liver disease by modifying lipid metabolism via AMPK

• Published in: International journal of biological macromolecules Vol. 279; no. Pt 4; p. 135565
• Main Authors: Lv, Rui, Cao, Houkang, Zhong, Mingli, Wu, Jianzhao, Lin, Shiyuan, Li, Bo, Chen, Dongyu, Zhang, Zhiyuan, Zhang, Kefeng, Gao, Ya
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2024
• Subjects: Alcoholic fatty liver disease; AMPK; Polygala fallax Hemsl polysaccharides; Hadha; ADH; ALP; HFD; ALT; MDA; Fdft1; HDL-C; Acss2; Hmgcs1; Prkaa1; Prkaa2; Scd1; Acat2; H&E; Polygala fallax Hemsl polysaccharides; Lss; Pmvk; Gstp1; ROS; AMPK; Mvd; CYP2E1; Gstt1; Msmo1; Acsl4; PFPs; GAPDH; Acaca; Fdps; Idi1; Hsd17b7; AFLD; Mvk; Gsta3; LDL-C; Acad11; Sqle; Adh4; Gstm3; OA; p-AMPK; Fasn; Elovl6; CC; AST; GSH-Px; Fabp4; Nsdhl; SOD; Dhcr7; SREBP-1c; CYP7a1; TC; ALDH; Cpt1a; TG; Hmgcr; Alcoholic fatty liver disease
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135565

Alcoholic fatty liver disease (AFLD) is characterized by excessive lipid accumulation in the liver. This study aimed to investigate the protective effects and mechanisms of Polygala fallax Hemsl polysaccharides (PFPs) on AFLD. PFPs were purified and structurally characterized. An AFLD model was established in mice using alcohol and a high-fat diet. A significant reduction in hepatic steatosis was observed following PFPs treatment, evidenced by decreased fat deposition in liver tissues. Additionally, PFPs reduced various liver injury markers, increased levels of antioxidant enzymes, and improved significantly liver function. RNA sequencing revealed that PFPs improved lipid and CYP450 metabolic pathway abnormalities in AFLD mice. Furthermore, PFPs activated the AMPK pathway, reducing lipid accumulation and enhancing lipid metabolism. A HepG2 cell model treated with ethanol and oleic acid showed significant biochemical improvements with PFPs pretreatment, including reduced lipid accumulation and lower reactive oxygen species (ROS) levels. To further elucidate the AMPK and PFPs correlation in AFLD, an AMPK inhibitor (compound C) was used. In vitro and in vivo qRT-PCR and Western blot results confirmed that PFPs protected against AFLD by activating AMPK phosphorylation, regulating lipid synthesis, and inhibiting lipid accumulation. PFPs also modulated CYP2E1 and oxidative stress-related gene expression, affecting liver metabolism. [Display omitted] •The study revealed PFP1's structure as a complex rhamnogalacturonan with 1,4-D-GalpA, 1,2,4-L-Rhap, T-D-Galp, and 1,5-L-Araf.•The key to alleviating alcoholic fatty liver disease is to inhibit lipid synthesis.•Analyzed key AMPK pathways and differentially expressed genes affected by PFPs.•Findings reveal that PFPs effectively regulate lipid metabolism and exhibit antioxidant and hepatoprotective properties.•PFPs demonstrated promising potential for enhancing liver health management.