Dihydroisocoumarin Derivatives from Marine-Derived Fungal Isolates and Their Anti-inflammatory Effects in Lipopolysaccharide-Induced BV2 Microglia

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• 作者：Dong-Cheol Kim ; Tran Hong Quang ; Nguyen Thi Thanh Ngan ; Chi-Su Yoon ; Jae Hak Sohn ; Joung Han Yim ; Yu Feng ; Yongsheng Che ; Youn-Chul Kim ; Hyuncheol Oh
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：December 24, 2015
• 年：2015
• 卷：78
• 期：12
• 页码：2948-2955
• 全文大小：435K
• ISSN：1520-6025

文摘

Chemical investigation of the EtOAc extracts of marine-derived fungal isolates Aspergillus sp. SF-5974 and Aspergillus sp. SF-5976 yielded a new dihydroisocoumarin derivative (1) and 12 known metabolites. The structures of the isolated metabolites were established by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Among the metabolites, the absolute configuration of 5′-hydroxyasperentin (6) was determined by single-crystal X-ray diffraction analysis. The in vitro antineuroinflammatory effects of the metabolites were also evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Among the isolated metabolites, dihydroisocoumarin derivatives 1–6 (10–80 μM) were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated BV2 microglia. Further, 1 (20–80 μM) was found to suppress the phosphorylation of the inhibitor of nuclear factor kappa B-α (IκB-α), interrupt the nuclear translocation of nuclear factor kappa B (NF-κB), and decrease the activation of p38 mitogen-activated protein kinase (MAPK).