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<p>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 (<b>1</b>), along with its structural analogs, Chikusetsusaponins IVa (<b>2</b>), IV (<b>3</b>), and V (<b>4</b>), 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&#xa0;µM. A comparative analysis of the chemical structures and activities of all evaluated compounds, along with oleanolic acid (<b>5</b>), revealed that (i) disubstitution of glycosyl on <i>C</i>-3 and <i>C</i>-28 of oleanane aglycone was crucial to the promoting effect; (ii) 3-<i>O</i>-<i>β</i>-<i>D</i>-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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年5月7日

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

摘要

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