Oleanane-type triterpene saponins promote extracellular vesicle secretion of human adipose-derived mesenchymal stem cells

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2025-05-07 DOI:10.1007/s11418-025-01908-4

Jianyu Lin, Hongqiang Lin, Kohei Sato, Atsushi Kimishima, Satoru Tamura, Kazuki Ujiie, Chitose Oneyama, Jinping Liu, Masayoshi Arai

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Abstract

The application of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) holds significant promise in anti-aging cosmetics, regenerative medicine, and drug delivery systems. However, their limited production efficiency remains a critical barrier to advancing related therapies and pharmaceutical applications. In this study, a library of triterpene saponins was screened, leading to the re-discovery of an oleanane-type triterpene saponin Lucyoside H (1), along with its structural analogs, Chikusetsusaponins IVa (2), IV (3), and V (4), which were found to increase the production of EV from human adipose-derived mesenchymal stem cells (ADMSCs) at a concentration ranging from 10 to 100 µM. A comparative analysis of the chemical structures and activities of all evaluated compounds, along with oleanolic acid (5), revealed that (i) disubstitution of glycosyl on C-3 and C-28 of oleanane aglycone was crucial to the promoting effect; (ii) 3-O-β-D-glucuronopyranosyl substitution achieved the highest efficiency in the promoting effect and alteration of this group attenuated the activity. These results highlight the potential for developing a natural product-based approach to increase EV production by MSCs.

Graphical abstract

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齐墩烷型三萜皂苷促进人脂肪源性间充质干细胞胞外囊泡分泌。

间充质干细胞（MSC）衍生的细胞外囊泡（EVs）在抗衰老化妆品、再生医学和药物输送系统方面的应用具有重要的前景。然而，它们有限的生产效率仍然是推进相关治疗和制药应用的关键障碍。在本研究中，筛选了一个三萜皂苷文库，重新发现了齐烷型三萜皂苷Lucyoside H(1)及其结构类似物Chikusetsusaponins IVa(2)、IV(3)和V(4)，发现它们在10至100µM的浓度范围内可以增加人脂肪源性间充质干细胞（ADMSCs）的EV产量。与齐墩果酸(5)相比，对所有被评价化合物的化学结构和活性分析表明：(1)齐墩果酸苷元C-3和C-28上的糖基二取代对促进作用至关重要；（ii） 3-O-β- d -葡萄糖醛酸吡喃基取代的促进作用最高，该组的改变使活性减弱。这些结果强调了开发一种基于天然产物的方法来增加msc的EV产量的潜力。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.