Targeting inflammatory dysregulation in metabolic dysfunction-associated steatotic liver disease rat model: the preventive and therapeutic effects of acetyl-11-keto-beta-boswellic acid.

Metabolic associated fatty liver disease (MASLD) is a global health issue affecting over 30% of the population and can progress to severe liver conditions such as cirrhosis and hepatocellular carcinoma (HCC). The progression of MASLD is driven by underlying metabolic dysregulation and chronic inflammation. This study aims to evaluate the therapeutic efficacy of acetyl-11-keto-β-boswellic acid (AKBA) in a rat model of MASLD induced by a high-fat and high-fructose diet (HFrD). We hypothesize that AKBA supplementation will suppress pro-inflammatory cytokine expression and inhibit inflammatory signaling pathways, thereby ameliorating MASLD progression. MASLD was induced in 36 male rats, randomly divided into two main groups: prevention (6-week regimen) and treatment (8-week regimen). Each group was further divided into three subgroups: Control, HFrD, and AKBA. In the prevention group, the subgroup receiving a high-fat, high-fructose diet (HFrD) was simultaneously administered AKBA. In the treatment group, after inducing MASLD with HFrD, AKBA was administered as a therapeutic intervention. Serum levels of IL-2, pro-inflammatory cytokines (IL-1β, IL-18, IL-1α), and anti-inflammatory cytokines (IL-1Ra, IL-10) were measured using ELISA. Additionally, IL-1R1 gene expression was analyzed using quantitative real-time PCR. Histological examinations of liver tissues were conducted to assess triglyceride accumulation. AKBA significantly reduced serum levels of pro-inflammatory cytokines, including IL-1α, IL-1β, and IL-18, which are key products of the NLRP3 inflammasome complex, as well as reduced IL-2 serum levels. It also increased levels of the anti-inflammatory cytokines IL-1Ra and IL-10. Additionally, AKBA mitigated weight gain and decreased triglyceride accumulation in liver tissues compared to the HFrD group. AKBA exhibits potent anti-inflammatory properties that ameliorate MASLD by reducing hepatic steatosis and inflammatory markers. Further studies, including extended durations and human clinical trials, are warranted to fully elucidate AKBA's therapeutic potential.