title: Dihydroisocoumarin Derivatives from Marine-Derived Fungal Isolates and Their Anti-inflammatory Effects in Lipopolysaccharide-Induced BV2 Microglia.
abstract: 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).
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.|Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST) , 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam.
authors.forename: Tran Hong
authors.initials: TH
authors.lastname: Quang
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.|Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST) , 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam.
authors.forename: Nguyen Thi Thanh
authors.initials: NT
authors.lastname: Ngan
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.
authors.forename: Chi-Su
authors.initials: CS
authors.lastname: Yoon
authors.affiliation: College of Medical and Life Sciences, Silla University , Busan 617-736, Republic of Korea.
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Korea Polar Research Institute, KORDI , 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea.
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Beijing Ditan Hospital, Capital Medical University , Beijing 100015, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Beijing Institute of Pharmacology & Toxicology , Beijing 100850, People's Republic of China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Che
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001230:Aspergillus / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D020672:I-kappa B Proteins; D049934:Isocoumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008386:Marine Biology; D017628:Microglia / Q000187:drug effects*; D015394:Molecular Structure; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C000607239:5'-hydroxyasperentin; D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D049934:Isocoumarins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone