Ehtiati Sajad, Pakrad Roya, Khatami Seyyed Hossein, Kachouei Reza Ataei, Doagoo Alireza, Lanjanian Hossein, Ghazizadeh Hashemi Seyyed Amir Hossein, Hamed Nastaran, Hatami Behzad, Ahmadzade Reyhane, Salmani Farzaneh, Karima Saeed
Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 6. doi: 10.1007/s00210-025-04340-3.
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.
代谢相关脂肪性肝病（MASLD）是一个全球性的健康问题，影响着超过30%的人口，并且可能进展为严重的肝脏疾病，如肝硬化和肝细胞癌（HCC）。MASLD的进展是由潜在的代谢失调和慢性炎症驱动的。本研究旨在评估乙酰-11-酮-β-乳香酸（AKBA）在高脂高果糖饮食（HFrD）诱导的MASLD大鼠模型中的治疗效果。我们假设补充AKBA将抑制促炎细胞因子的表达并抑制炎症信号通路，从而改善MASLD的进展。将36只雄性大鼠诱导建立MASLD模型，随机分为两个主要组：预防组（6周方案）和治疗组（8周方案）。每组再进一步分为三个亚组：对照组、HFrD组和AKBA组。在预防组中，接受高脂高果糖饮食（HFrD）的亚组同时给予AKBA。在治疗组中，用HFrD诱导MASLD后，给予AKBA作为治疗干预。使用酶联免疫吸附测定法（ELISA）测量血清白细胞介素-2（IL-2）、促炎细胞因子（IL-1β、IL-18、IL-1α）和抗炎细胞因子（IL-1受体拮抗剂（IL-1Ra）、IL-10）的水平。此外，使用定量实时聚合酶链反应（PCR）分析IL-1R1基因表达。对肝组织进行组织学检查以评估甘油三酯的积累。AKBA显著降低了促炎细胞因子的血清水平，包括NLRP3炎性小体复合物的关键产物IL-1α、IL-1β和IL-18，以及降低了IL-2的血清水平。它还增加了抗炎细胞因子IL-1Ra和IL-10的水平。此外，与HFrD组相比，AKBA减轻了体重增加并减少了肝组织中甘油三酯的积累。AKBA具有强大的抗炎特性，通过减少肝脂肪变性和炎症标志物来改善MASLD。有必要进行进一步的研究，包括延长研究时间和开展人体临床试验，以充分阐明AKBA的治疗潜力。
