Total Saponins from Panax japonicus Reduced Lipid Deposition and Inflammation in Hepatocyte via PHD2 and Hepatic Macrophage-derived Exosomal miR-463-5p

Jingjie Yang; Yibei Gui; Ying Zheng; Haodong He; Lihan Chen; Tongtong Li; Haoran Liu; Dongshuo Wang; Ding Yuan; Chengfu Yuan

doi:10.1016/j.jep.2025.119376

Total Saponins from Panax japonicus Reduced Lipid Deposition and Inflammation in Hepatocyte via PHD2 and Hepatic Macrophage-derived Exosomal miR-463-5p

J Ethnopharmacol. 2025 Jan 20:119376. doi: 10.1016/j.jep.2025.119376. Online ahead of print.

Authors

Jingjie Yang¹, Yibei Gui², Ying Zheng³, Haodong He⁴, Lihan Chen⁵, Tongtong Li⁶, Haoran Liu⁷, Dongshuo Wang⁸, Ding Yuan⁹, Chengfu Yuan¹⁰

Affiliations

¹ 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. Electronic address: [email protected].
² 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. Electronic address: [email protected].
³ 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. Electronic address: [email protected].
⁴ 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. Electronic address: [email protected].
⁵ 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. Electronic address: [email protected].
⁶ 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. Electronic address: [email protected].
⁷ 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. Electronic address: [email protected].
⁸ College of Basic Medical Science, China Three Gorges University, Yichang 443002, China. Electronic address: [email protected].
⁹ Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China; College of Medicine and Health Science, China Three Gorges University, Yichang, 443002, China. Electronic address: [email protected].
¹⁰ 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. Electronic address: [email protected].

PMID: 39842748
DOI: 10.1016/j.jep.2025.119376

Abstract

Ethnopharmacological relevance: 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).

Aim of study: Evaluate the therapeutic effects of TSPJ on lipid metabolism disorders in a NASH model and explore the possible underlying mechanisms.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: PHD2; Panax japonicus (T. Nees) C.A. Mey.; exosomes; lipid metabolism; miR-463-5p; non-alcoholic steatohepatitis; total saponins.