Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Total saponins from Panax japonicus inhibit phosphatidylcholine hydrolysis and relieve hepatic steatosis via the miR-1a-3p/PLD1 pathway.
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Yang Ning, Yang Jingjie, Shi Yulan, Wang Shuwen, Yao Qianqian, Yuan Chengfu
Аннотация
BACKGROUND: Panax japonicus (T. Nees) C.A. Mey., a member of the Araliaceae family, has been utilized for medicinal purposes by the Tujia and Hmong ethnic groups in China for over a thousand years. In traditional Chinese medicine, metabolic dysfunction-associated fatty liver disease (MAFLD) is classified as a damp-heat syndrome, and P. japonicus is believed to strengthen the spleen and the stomach, promoting fat transformation. Previous studies have shown that the total saponins from P. japonicus (TSPJ) are the primary active constituents that exert hepatoprotective, lipid-lowering, and anti-inflammatory effects in the advanced stages of MAFLD.
PURPOSE: This work examines the effects of TSPJ on early stage MAFLD (i.e., hepatic steatosis) and explores their potential as a novel therapeutic strategy to prevent disease progression.
METHODS: Animal models were created by administering a high-fat diet (HFD) to mice, and cell models were established by stimulating AML12 hepatocytes with palmitic acid (PA). The changes in lipid metabolism in the models receiving TSPJ, having miR-1a-3p knockdown, and/or having PLD1 knockdown were examined using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence, etc. Non-targeted metabolomic analysis was employed to detect the effects of TSPJ on lipid species.
RESULTS: For the mouse model, TSPJ significantly reduced body weight (p < 0.001) and liver weight (p < 0.001) and improved liver function. For both the mouse and cell models, TSPJ decreased lipid accumulation (p = 0.05) and inhibited the expression of the lipogenic genes Acaca (p < 0.001; p = 0.02), Fasn (p = 0.008; p = 0.001), and Scd1 (p = 0.05; p = 0.05). According to non-targeted metabolomic analysis, phosphatidylcholine (PC) was the primary lipid species affected by TSPJ. PLD1, which is a downstream target of miR-1a-3p, was the crux in the regulation of lipid metabolism by TSPJ. The efficacy of TSPJ was lost when the models had miR-1a-3p knockdown.
CONCLUSIONS: TSPJ mitigated hepatocyte steatosis by upregulating miR-1a-3p, which inhibited PLD1 to reduce PC hydrolysis, ultimately decreasing hepatic lipid accumulation.
PURPOSE: This work examines the effects of TSPJ on early stage MAFLD (i.e., hepatic steatosis) and explores their potential as a novel therapeutic strategy to prevent disease progression.
METHODS: Animal models were created by administering a high-fat diet (HFD) to mice, and cell models were established by stimulating AML12 hepatocytes with palmitic acid (PA). The changes in lipid metabolism in the models receiving TSPJ, having miR-1a-3p knockdown, and/or having PLD1 knockdown were examined using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence, etc. Non-targeted metabolomic analysis was employed to detect the effects of TSPJ on lipid species.
RESULTS: For the mouse model, TSPJ significantly reduced body weight (p < 0.001) and liver weight (p < 0.001) and improved liver function. For both the mouse and cell models, TSPJ decreased lipid accumulation (p = 0.05) and inhibited the expression of the lipogenic genes Acaca (p < 0.001; p = 0.02), Fasn (p = 0.008; p = 0.001), and Scd1 (p = 0.05; p = 0.05). According to non-targeted metabolomic analysis, phosphatidylcholine (PC) was the primary lipid species affected by TSPJ. PLD1, which is a downstream target of miR-1a-3p, was the crux in the regulation of lipid metabolism by TSPJ. The efficacy of TSPJ was lost when the models had miR-1a-3p knockdown.
CONCLUSIONS: TSPJ mitigated hepatocyte steatosis by upregulating miR-1a-3p, which inhibited PLD1 to reduce PC hydrolysis, ultimately decreasing hepatic lipid accumulation.