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具有衰老细胞选择性的轮叶冷水花化学成分研究。

Chemical constituents with senolytic activity from the stems of Limacia scandens.

机构信息

Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea.

Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.

出版信息

Phytochemistry. 2023 Aug;212:113740. doi: 10.1016/j.phytochem.2023.113740. Epub 2023 May 24.

DOI:10.1016/j.phytochem.2023.113740
PMID:37236331
Abstract

While screening senotherapeutics from natural products, seven undescribed chemicals, two syringylglycerol derivatives, two cyclopeptides, one tigliane analogue, and two chromone derivatives, as well as six known compounds were isolated from the stems of Limacia scandens. The structures of compounds were elucidated through spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and CD data. All compounds were tested in replicative senescent human dermal fibroblasts (HDFs) to determine their potential as senotherapeutic agents to specifically target senescent cells. One tigliane and two chromones derivatives showed senolytic activity, indicating that senescent cells were selectively removed. Especially, 2-{2-[(3'-O-β-d-glucopyranosyl)phenyl]ethyl}chromone is expected to be a potential senotherapeutics by inducing HDF death, inhibiting the activity of senescence-associated β-galactosidase (SA-β-gal) and expressing senescence-associated secretory phenotype (SASP) factors.

摘要

在从天然产物中筛选衰老治疗药物时,从青藤茎中分离得到了七种未描述的化学物质,两种丁香基甘油衍生物,两种环肽,一种丁香烷类似物和两种色酮衍生物,以及六种已知化合物。通过包括 1D 和 2D NMR、HRESIMS 和 CD 数据在内的光谱数据分析阐明了化合物的结构。所有化合物均在复制性衰老的人真皮成纤维细胞(HDF)中进行了测试,以确定它们作为专门针对衰老细胞的衰老治疗药物的潜力。一种丁香烷和两种色酮衍生物表现出溶衰老细胞活性,表明选择性地去除了衰老细胞。特别是,2-{2-[(3'-O-β-d-吡喃葡萄糖基)苯]乙基}色酮有望通过诱导 HDF 死亡、抑制衰老相关β-半乳糖苷酶(SA-β-gal)活性和表达衰老相关分泌表型(SASP)因子成为一种潜在的衰老治疗药物。

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