2. Academic Validation
  3. Dihydroisocoumarin Derivatives from Marine-Derived Fungal Isolates and Their Anti-inflammatory Effects in Lipopolysaccharide-Induced BV2 Microglia

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

  • J Nat Prod. 2015 Dec 24;78(12):2948-55. doi: 10.1021/acs.jnatprod.5b00614.
Dong-Cheol Kim 1,  Tran Hong Quang 1 2,  Nguyen Thi Thanh Ngan 1 2,  Chi-Su Yoon 1,  Jae Hak Sohn 3,  Joung Han Yim 4,  Yu Feng 5,  Yongsheng Che 6,  Youn-Chul Kim 1,  Hyuncheol Oh 1
Affiliations

Affiliations

  • 1 Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University , Iksan 570-749, Republic of Korea.
  • 2 Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST) , 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam.
  • 3 College of Medical and Life Sciences, Silla University , Busan 617-736, Republic of Korea.
  • 4 Korea Polar Research Institute, KORDI , 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea.
  • 5 Beijing Ditan Hospital, Capital Medical University , Beijing 100015, People's Republic of China.
  • 6 Beijing Institute of Pharmacology & Toxicology , Beijing 100850, People's Republic of China.
PMID: 26651366 DOI: 10.1021/acs.jnatprod.5b00614
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).

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