{"title":"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。","authors":"Jianyu Lin, Hongqiang Lin, Kohei Sato, Atsushi Kimishima, Satoru Tamura, Kazuki Ujiie, Chitose Oneyama, Jinping Liu, Masayoshi Arai","doi":"10.1007/s11418-025-01908-4","DOIUrl":null,"url":null,"abstract":"<div><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 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><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"922 - 930"},"PeriodicalIF":2.5000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oleanane-type triterpene saponins promote extracellular vesicle secretion of human adipose-derived mesenchymal stem cells\",\"authors\":\"Jianyu Lin, Hongqiang Lin, Kohei Sato, Atsushi Kimishima, Satoru Tamura, Kazuki Ujiie, Chitose Oneyama, Jinping Liu, Masayoshi Arai\",\"doi\":\"10.1007/s11418-025-01908-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><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 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><h3>Graphical abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":654,\"journal\":{\"name\":\"Journal of Natural Medicines\",\"volume\":\"79 4\",\"pages\":\"922 - 930\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Natural Medicines\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11418-025-01908-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Medicines","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11418-025-01908-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
摘要
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。
Oleanane-type triterpene saponins promote extracellular vesicle secretion of human adipose-derived mesenchymal stem cells
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.
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.