Curcumin’s dual effect on pyroptosis and autophagy in metabolic- associated fatty liver disease: a potential therapeutic strategy

Abstract

Metabolic-associated fatty liver disease (MAFLD) has become a considerable public health concern due to its elevated prevalence and its probability of progressing into hepatocellular carcinoma. Autophagy and pyroptosis are key cellular processes involved in MAFLD progression, with autophagy acting as a protective mechanism by inhibiting inflammasome activation. At the same time, excessive pyroptosis contributes to inflammation and tissue damage. Gasdermin D (GSDMD), a key executor of pyroptosis, plays a central role in this process by mediating inflammatory cell death and has emerged as a potential marker of liver injury severity. This study evaluates curcumin’s effects on liver fat accumulation, inflammatory cytokine levels, oxidative stress, and its potential to regulate autophagy and pyroptosis. Rats were allocated to three groups. Group I established a normal diet for twelve weeks. Group II was given a high-fat, high-fructose diet (HFFD) for twelve weeks. Group III received the HFFD diet for twelve weeks with curcumin supplementation from the 6th to the 12th week. Rats in Group III showed significant improvements in adiposity, lipid metabolism, oxidative stress, and inflammatory markers. Histopathological analysis confirmed the beneficial effects of curcumin, with notable improvements in liver structure and reduced Lipid-associated liver dysfunction severity. Furthermore, curcumin’s dual effects on autophagy through modulation of P62 protein and BECN1 gene and on pyroptosis through inhibition of GSDMD activation, were evident, supporting its protective role in preventing MAFLD progression to fibrosis and liver cancer.