Anti-obesity Effects of Panax ginseng-derived exosomes via AMPK-mediated inhibition of adipocyte differentiation and lipogenesis

IF 5.8 3区化学 Q1 CHEMISTRY, MEDICINAL

Natural Products and Bioprospecting Pub Date : 2026-01-09 DOI:10.1007/s13659-025-00561-4

Min Ho Han, Sun Hye Lee, Youn Seon Hwang, Jong Hyun Oh, Jin Woo Kim

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Abstract

This study investigated the anti-obesity potential of Panax ginseng-derived exosomes (PGE) by evaluating their influence on energy metabolism, adipogenesis, and lipid accumulation. PGEs were isolated using a tangential flow filtration system, yielding particles with an average diameter of 159.5 nm and a concentration of 3.9 × 10¹² particles/mL. In 3T3-L1 preadipocytes, PGE treatment resulted in a 72.1% reduction in lipid accumulation, as demonstrated by Oil Red O staining, indicating significant inhibition of adipogenic differentiation. Elevated expression of surface markers TET-8 (147.2%) verified the exosomal nature of the isolated vesicles. To determine their role in adipocyte differentiation, we analyzed gene and protein expression of key adipogenic markers–peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer-binding protein alpha and beta, and fatty acid-binding protein 4-revealing reductions of 23.6–35.6% and 26.7–35.2%, respectively. These results indicate downregulation of transcriptional and translational pathways driving adipogenesis. Lipogenic regulators, including sterol regulatory element-binding protein 1c, acetyl-CoA carboxylase, and fatty acid synthase, were also suppressed by 24.9–41.0% (gene) and 22.8–24.5% (protein), indicating impaired fatty acid synthesis. Conversely, AMP-activated protein kinase (AMPK) expression increased by up to 53.8% (gene) and 47.9% (protein), implying activation of energy homeostasis signaling. Immunofluorescence analysis showed a reduction in the MitoTracker/DAPI ratio (57.7–60.0%) and an increase in the F-actin/DAPI ratio (39.5–60.8%), indicating decreased mitochondrial activity and enhanced cytoskeletal integrity. These molecular changes were accompanied by AMPK activation and PPAR-γ inhibition. Collectively, these findings underscore the potential of PGEs as bioactive agents for obesity management by concurrently inhibiting adipogenesis and lipogenesis, providing a strong basis for their application in anti-obesity functional foods and pharmaceutical products.

Graphic Abstract

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人参来源的外泌体通过ampk介导的脂肪细胞分化和脂肪生成抑制的抗肥胖作用

本研究通过评估人参源性外泌体（PGE）对能量代谢、脂肪生成和脂质积累的影响来研究其抗肥胖潜力。采用切向流过滤系统分离PGEs，得到的颗粒平均直径为159.5 nm，浓度为3.9 × 1012个/mL。在3T3-L1前脂肪细胞中，PGE处理导致脂质积累减少72.1%，如油红O染色所示，表明显著抑制脂肪形成分化。表面标记物TET-8的表达升高（147.2%）证实了分离囊泡的外泌体性质。为了确定它们在脂肪细胞分化中的作用，我们分析了关键脂肪生成标志物——过氧化物酶体增殖物激活受体γ (PPAR-γ)、CCAAT/增强子结合蛋白α和β以及脂肪酸结合蛋白4的基因和蛋白表达，结果显示，它们分别减少了23.6% - 35.6%和26.7% - 35.2%。这些结果表明，下调转录和翻译途径驱动脂肪形成。脂肪生成调节因子，包括甾醇调节元件结合蛋白1c、乙酰辅酶a羧化酶和脂肪酸合成酶，也被抑制24.9-41.0%（基因）和22.8-24.5%（蛋白质），表明脂肪酸合成受损。相反，amp激活的蛋白激酶（AMPK）表达增加了53.8%（基因）和47.9%（蛋白质），表明激活了能量稳态信号。免疫荧光分析显示MitoTracker/DAPI比值降低（57.7-60.0%），F-actin/DAPI比值升高（39.5-60.8%），表明线粒体活性降低，细胞骨架完整性增强。这些分子变化伴随着AMPK的激活和PPAR-γ的抑制。总的来说，这些发现强调了PGEs作为生物活性剂的潜力，通过同时抑制脂肪生成和脂肪生成，为其在抗肥胖功能食品和药品中的应用提供了强有力的基础。图形抽象

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.