Lin Jianyu, Lin Hongqiang, Sato Kohei, Kimishima Atsushi, Tamura Satoru, Ujiie Kazuki, Oneyama Chitose, Liu Jinping, Arai Masayoshi
Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka, 565-0871, Japan.
School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun, 130021, People's Republic of China.
J Nat Med. 2025 May 7. doi: 10.1007/s11418-025-01908-4.
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.
间充质干细胞（MSC）衍生的细胞外囊泡（EVs）在抗衰老化妆品、再生医学和药物递送系统中的应用具有重大前景。然而，其有限的生产效率仍然是推进相关治疗和药物应用的关键障碍。在本研究中，对三萜皂苷文库进行了筛选，重新发现了一种齐墩果烷型三萜皂苷露水草苷H（1）及其结构类似物，如竹节人参皂苷IVa（2）、IV（3）和V（4），发现它们在10至100µM的浓度范围内可增加人脂肪来源间充质干细胞（ADMSCs）的EV产量。对所有评估化合物以及齐墩果酸（5）的化学结构和活性进行的比较分析表明：（i）齐墩果烷苷元C-3和C-28上糖基的双取代对促进作用至关重要；（ii）3-O-β-D-葡萄糖醛酸吡喃糖基取代在促进作用方面效率最高，改变该基团会减弱活性。这些结果突出了开发一种基于天然产物的方法来提高MSC产生EV的潜力。
