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1.
Neurochem Int ; 95: 55-62, 2016 May.
Article in English | MEDLINE | ID: mdl-26724567

ABSTRACT

In the course of searching for anti-neuroinflammatory metabolites from marine fungi, citreohybridonol was isolated from marine-derived fungal strain Toxicocladosporium sp. SF-5699. Citreohybridonol inhibited production of nitric oxide (NO) and prostaglandin E2 (PGE2) in BV2 cells stimulated by lipopolysaccharide (LPS). Citreohybridonol also suppressed the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and other pro-inflammatory cytokines including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the LPS-stimulated cells. In the further study, citreohybridonol disturbed nuclear translocation of nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells by inhibiting the phosphorylation of the inhibitor kappa B-α (IκB-α). Citreohybridonol also had inhibitory effect on the LPS-stimulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Finally, citreohybridonol suppressed the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS-induced BV2 cells. These results suggest that citreohybridonol has anti-neuroinflammatory effect in LPS-stimulated BV2 cells by modulating TLR4-mediated several inflammatory pathways such as NF-κB and p38 MAPK pathways.


Subject(s)
Androstadienes/pharmacology , Anti-Inflammatory Agents/pharmacology , MAP Kinase Signaling System/drug effects , Myeloid Differentiation Factor 88/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Toll-Like Receptor 4/antagonists & inhibitors , Androstadienes/isolation & purification , Animals , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/physiology , Mice , Myeloid Differentiation Factor 88/biosynthesis , NF-kappa B/metabolism , Toll-Like Receptor 4/biosynthesis
2.
Arch Pharm Res ; 38(11): 2066-75, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25981820

ABSTRACT

A new isoprenylated flavonoid, 2S-5,7,2',4'-tetrahydroxy-3',5'-di-(γ,γ-dimethylallyl)flavanone, sanggenol Q (1), along with seven known isoprenylated flavonoids, sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5), sanggenon F (6), sanggenol O (7), and sanggenon N (8), three known Diels-Alder type adducts, sanggenon G (9), mulberrofuran G (10), and mulberrofuran C (11), and a known benzofuran, moracin E (12), were isolated from the root bark of Morus alba using silica gel, ODS, and Sephadex LH-20 column chromatography. Chemical structures were determined based on spectroscopic data analyses including NMR, MS, CD, and IR. For the first time, compounds 1 and 7 were isolated from the root bark of M. alba. All compounds were evaluated for hepatoprotective activity on t-BHP-induced oxidative stress in HepG2 cells and neuroprotective activity on glutamate-induced cell death in HT22 cells. Compounds 1, 4, 8, 10, and 11 showed protective effects on t-BHP-induced oxidative stress with EC50 values of 6.94 ± 0.38, 30.32 ± 6.82, 23.45 ± 4.72, 15.31 ± 2.21, and 0.41 ± 0.48 µM, respectively, and compounds 1, 2, 10, 11, and 12 showed protective effects on glutamate-induced cell death with EC50 values of 5.54 ± 0.86, 34.03 ± 7.71, 19.71 ± 0.71, 16.50 ± 7.82, and 1.02 ± 0.13 µM, respectively.


Subject(s)
Flavonoids/pharmacology , Morus/chemistry , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Animals , Cell Death/drug effects , Cell Line , Flavonoids/isolation & purification , Glutamic Acid/toxicity , Hep G2 Cells , Humans , Mice , Neuroprotective Agents/isolation & purification , Plant Bark , Plant Roots , Spectrum Analysis , tert-Butylhydroperoxide/toxicity
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