Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Department of Geriatrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Lipids Health Dis. 2023 Feb 10;22(1):22. doi: 10.1186/s12944-023-01787-2.
Nonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown.
In vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5-6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry.
Overexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway.
This study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.
非酒精性脂肪性肝炎（NASH）是目前最常见的肝脏疾病之一，目前尚无根治方法。先前已有多种人参皂苷化合物对此种情况的影响的报道，然而，单体人参皂苷 Rg1（Rg1）及其相关的潜在分子机制的具体作用仍不清楚。
在体外，通过向 HepG2 细胞暴露游离脂肪酸（FFAs）构建细胞模型。还建立了 5-6 周治疗的蛋氨酸和胆碱缺乏（MCD）诱导的 NASH 小鼠模型。Rg1 是一种中药单体。用 Rg1 处理这些 NASH 模型，并通过 qRT-PCR、Western Blot、测序、油红 O 染色、免疫荧光、酶活性、HE 染色、ELISA、双荧光素酶报告基因检测和免疫组织化学进行分析。
自噬相关蛋白 ATG2B 的过表达可减轻脂滴堆积，并降低已建立的 NASH 小鼠和细胞模型中的 ALT、AST、炎症细胞因子、过氧化氢和焦亡，同时增加 ATP 和自噬水平。miR-375-3p 和 ATG2B 的结合位点通过生物信息学预测和双荧光素酶报告基因得到验证。miR-375-3p 的敲低促进了自噬并抑制了焦亡。ATG2B 的敲低显著减弱了 miR-375-3p 对 NASH 的影响。Rg1 似乎通过 miR-375-3p 和 ATG2B 在体外和体内调节 NASH 炎症的发生和发展，并且受到 PTEN-AKT 通路的调节。
本研究表明，Rg1 通过 miR-375-3p/ATG2B/PTEN-AKT 通路参与自噬和焦亡，从而缓解 NASH 的发生和发展，因此揭示 Rg1 可作为 NASH 的候选药物。
