Non-alcoholic steatohepatitis (NASH) is a global public health concern that may progress into fibrosis, cirrhosis, and liver cancer, with limited curative treatment options. While the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is closely linked to NASH progression, nicotinic acid (NA), a vitamin used for the treatment of dyslipidemia, is an emerging pharmaceutical treatment for hepatic steatosis and fibrosis. Here, we investigated pharmacological effects of NA on experimental NASH and whether NLRP3 inflammasome/pyroptosis inhibition is an associated mechanism of action. Rats were fed a high-fat sucrose diet supplemented with cholesterol and a low dose of CCl₄. NA significantly reduced inflammation by decreasing the protein levels of tumor necrosis factor-alpha and nuclear factor kappa B. Moreover, NA inhibited the formation of NLRP3- apoptosis-associated speck-like protein containing caspase recruitment domain-Caspase-1, decreasing interleukin-1beta, interleukin-18, and gasdermin D protein. In addition, NA reduced tumor growth factor-beta, alpha-smooth muscle actin, and hepatic levels of collagen-1, consequently decreasing extracellular matrix synthesis. Our results indicate that NA can inhibit NASH progression and encourage further basic and clinical studies on the use of NA for the treatment of human NASH.

非酒精性脂肪性肝炎 (NASH) 是一个全球性的公共卫生问题，可能会发展为纤维化、肝硬化和肝癌，而治疗选择有限。虽然核苷酸结合寡聚化结构域样受体家族含热蛋白结构域 3 (NLRP3) 炎症小体与 NASH 进展密切相关，但烟酸 (NA) 作为一种用于治疗血脂异常的维生素，是一种新兴的治疗肝脂肪变性的药物和纤维化。在这里，我们研究了 NA 对实验性 NASH 的药理作用，以及 NLRP3 炎性体/细胞焦亡抑制是否是相关的作用机制。_{给大鼠喂食补充有胆固醇和低剂量CCl 4}的高脂肪蔗糖饮食。NA 通过降低肿瘤坏死因子-α 和核因子 kappa B 的蛋白水平，显着减轻炎症。此外，NA 还抑制 NLRP3（含有 caspase 募集结构域的凋亡相关斑点样蛋白 -Caspase-1）的形成，从而减少白细胞介素 1beta 、IL-18 和 Gasdermin D 蛋白。此外，NA 还降低了肿瘤生长因子-β、α-平滑肌肌动蛋白和肝脏 1 型胶原蛋白的水平，从而减少了细胞外基质的合成。我们的结果表明，NA 可以抑制 NASH 进展，并鼓励进一步使用 NA 治疗人类 NASH 的基础和临床研究。