Yang Jingjie, Gui Yibei, Zheng Ying, He Haodong, Chen Lihan, Li Tongtong, Liu Haoran, Wang Dongshuo, Yuan Ding, Yuan Chengfu
Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China; College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
J Ethnopharmacol. 2025 Feb 27;342:119376. doi: 10.1016/j.jep.2025.119376. Epub 2025 Jan 20.
Panax japonicus (T. Nees) C.A. Mey. (PJ) is a traditional Chinese herbal medicine revered as the "King of Herbs" in Tujia and Hmong medical practices. Clinically, it is primarily used to treat weakness and fatigue, wound bleeding, arthritis, hyperlipidemia, and fatty liver. It is rich in saponins, and the total saponins from PJ (TSPJ), possess immunomodulatory, antioxidant, and lipid-lowering effects. These properties hold significant potential in managing liver-related metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
Evaluate the therapeutic effects of TSPJ on lipid metabolism disorders in a NASH model and explore the possible underlying mechanisms.
To model NASH, C57BL/6J mice were fed a high-fat diet (HFD) and RAW264.7 cells were stimulated with lipopolysaccharide (LPS) and palmitic acid (PA). The animal and cell models were also treated with TSPJ, and the changes in inflammation and lipid metabolism were measured. Additional models were created by transfecting lentiviral vectors to cause miR-463-5p knockdown in the C57BL/6J mouse and the RAW264.7 cells.
In the HFD-induced mice, TSPJ reduced the body weight and liver weight, lowered the serum levels of TG, T-CHO, ALT, and AST, and reduced the hepatic lipid droplet formation and vacuolization. In the RAW264.7 cells, TSPJ upregulated the M2 markers and downregulated the M1 markers. TSPJ also significantly increased the expression of miR-463-5p in the exosomes derived from the RAW264.7 cells or the primary mouse hepatic macrophages, and miR-463-5p suppressed the expression of PHD2 in hepatocytes to improve lipid metabolism. However, when the exosome secretion inhibitor GW4869 was applied, TSPJ became less effective in alleviating the lipid deposition and inflammation in hepatocytes.
TSPJ significantly upregulated the expression of miR-463-5p in the exosomes of hepatic macrophages to thus downregulate PHD2 expression in hepatocytes and improve hepatic lipid metabolism.
三七（Panax japonicus (T. Nees) C.A. Mey.，PJ）是一种传统的中草药，在土家族和苗族医学中被誉为“草药之王”。临床上，它主要用于治疗虚弱和疲劳、伤口出血、关节炎、高脂血症和脂肪肝。它富含皂苷，三七总皂苷（TSPJ）具有免疫调节、抗氧化和降脂作用。这些特性在管理与肝脏相关的代谢性疾病如非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）方面具有巨大潜力。
评估TSPJ对NASH模型中脂质代谢紊乱的治疗效果，并探索可能的潜在机制。
为建立NASH模型，给C57BL/6J小鼠喂食高脂饮食（HFD），并用脂多糖（LPS）和棕榈酸（PA）刺激RAW264.7细胞。动物和细胞模型也用TSPJ处理，并测量炎症和脂质代谢的变化。通过转染慢病毒载体在C57BL/6J小鼠和RAW264.7细胞中敲低miR-463-5p来创建额外的模型。
在HFD诱导的小鼠中，TSPJ降低了体重和肝脏重量，降低了血清TG、T-CHO、ALT和AST水平，并减少了肝脏脂质滴形成和空泡化。在RAW264.7细胞中，TSPJ上调了M2标志物并下调了M1标志物。TSPJ还显著增加了RAW264.7细胞或原代小鼠肝巨噬细胞来源的外泌体中miR-463-5p的表达，并且miR-463-5p抑制了肝细胞中PHD2的表达以改善脂质代谢。然而，当应用外泌体分泌抑制剂GW4,869时，TSPJ在减轻肝细胞脂质沉积和炎症方面的效果变差。
TSPJ显著上调肝巨噬细胞外泌体中miR-463-5p的表达，从而下调肝细胞中PHD2的表达并改善肝脏脂质代谢。
