2. Academic Validation
  3. Oleanane-type triterpene saponins promote extracellular vesicle secretion of human adipose-derived mesenchymal stem cells

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

  • J Nat Med. 2025 Jul;79(4):922-930. doi: 10.1007/s11418-025-01908-4.
Jianyu Lin # 1,  Hongqiang Lin # 2 3 1,  Kohei Sato 1,  Atsushi Kimishima 1,  Satoru Tamura 4,  Kazuki Ujiie 4,  Chitose Oneyama 5,  Jinping Liu 6,  Masayoshi Arai 7
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka, 565-0871, Japan.
  • 2 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun, 130021, People's Republic of China.
  • 3 College of Basic Medical Sciences, Jilin University, Ximin Street 126, Changchun, 130021, People's Republic of China.
  • 4 School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichiban-cho, Wakayama-shi, Wakayama, 640-8156, Japan.
  • 5 Division of Cancer Cell Regulation, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
  • 6 School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun, 130021, People's Republic of China. liujp@jlu.edu.cn.
  • 7 Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka, 565-0871, Japan. araim@phs.osaka-u.ac.jp.
  • # Contributed equally.
PMID: 40335793 DOI: 10.1007/s11418-025-01908-4
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.

Keywords

Chikusetsusaponin; Extracellular vesicle; Mesenchymal stem cell; Oleanane-type triterpene saponin.

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