利用人参皂苷 Rd 激活 SIRT6 治疗小鼠非酒精性脂肪肝模型的治疗潜力,ACS Omega

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利用人参皂苷 Rd 激活 SIRT6 治疗小鼠非酒精性脂肪肝模型的治疗潜力
ACS Omega ( IF 3.7 ) Pub Date : 2023-08-03 , DOI: 10.1021/acsomega.3c04122
Tianqi Cui _{1,

2} , Xiaoxia Xiao ₂ , Zhisen Pan ₂ , Kaijia Tang ₂ , Yadi Zhong ₂ , Yingjian Chen ₂ , Jingyi Guo ₂ , Siwei Duan ₂ , Guangcheng Zhong ₂ , Tianyao Li ₂ , Xiang Li ₂ , Xiumei Wu ₃ , Chuanquan Lin ₂ , Xiaoying Yang ₄ , Yong Gao ₂ , Dong Zhang ₁

Affiliation

非酒精性脂肪性肝病（NAFLD）是一种全球流行的疾病，也是肝癌的常见前兆，但目前尚无特效药物可用于治疗。人参以其药用和饮食特性而闻名，已被用于 NAFLD 的治疗，尽管其确切的潜在机制仍然难以捉摸。为了研究人参皂苷 Rd 的有效性，我们采用小鼠和细胞模型，使用高脂肪饮食、油酸和棕榈酸诱导 NAFLD。我们通过对肝脏特异性敲除 SIRT6（一种参与代谢调节的关键蛋白）的小鼠进行实验，探索并证实了人参皂苷 Rd 诱导肝脂肪变性的具体机制。我们的研究结果表明，服用人参皂苷 Rd 可显着降低原代肝细胞中油酸和棕榈酸诱导的炎症反应、活性氧 (ROS) 水平、脂质过氧化物水平和线粒体应激，从而减轻过度的脂质积累。此外，人参皂苷 Rd 给药有效增强了参与脂肪酸氧化的关键蛋白的 mRNA 含量，特别是 SIRT6 及其靶蛋白。我们进一步验证了人参皂苷 Rd 直接与 SIRT6 结合，增强其脱乙酰酶活性。值得注意的是，我们发现，在肝脏特异性 SIRT6 敲除小鼠中，人参皂苷 Rd 对脂肪饮食引起的肝脏疾病的保护作用几乎完全逆转。我们的研究结果强调了人参皂苷 Rd 通过激活 SIRT6 在 NAFLD 治疗中的潜在治疗作用。这些结果值得进一步研究人参皂甙 Rd 的开发，作为治疗这种常见肝病的有前途的药物。

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Harnessing the Therapeutic Potential of Ginsenoside Rd for Activating SIRT6 in Treating a Mouse Model of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global condition and a common precursor to liver cancer, yet there is currently no specific medication available for its treatment. Ginseng, renowned for its medicinal and dietary properties, has been utilized in NAFLD management, although the precise underlying mechanism remains elusive. To investigate the effectiveness of ginsenoside Rd, we employed mouse and cell models to induce NAFLD using high-fat diets, oleic acid, and palmitic acid. We explored and confirmed the specific mechanism of ginsenoside Rd-induced hepatic steatosis through experiments involving mice with a liver-specific knockout of SIRT6, a crucial protein involved in metabolic regulation. Our findings revealed that administration of ginsenoside Rd significantly reduced the inflammatory response, reactive oxygen species (ROS) levels, lipid peroxide levels, and mitochondrial stress induced by oleic acid and palmitic acid in primary hepatocytes, thereby mitigating excessive lipid accumulation. Moreover, ginsenoside Rd administration effectively enhanced the mRNA content of key proteins involved in fatty acid oxidation, with a particular emphasis on SIRT6 and its target proteins. We further validated that ginsenoside Rd directly binds to SIRT6, augmenting its deacetylase activity. Notably, we made a significant observation that the protective effect of ginsenoside Rd against hepatic disorders induced by a fatty diet was almost entirely reversed in mice with a liver-specific SIRT6 knockout. Our findings highlight the potential therapeutic impact of Ginsenoside Rd in NAFLD treatment by activating SIRT6. These results warrant further investigation into the development of Ginsenoside Rd as a promising agent for managing this prevalent liver disease.

更新日期：2023-08-03

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