title: Sauchinone protects pancreatic β cells against cytokine-mediated toxicity.
abstract: Sauchinone has been shown to exert potent hepatoprotective, anti-inflammatory and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone on IL-1β (5 ng/ml) and IFN-γ (100 U/ml)-induced β-cell damage. Pre-treatment with sauchinone increased the viability of cytokine-treated RINm5F cells at concentrations of 20-40 μM. Sauchinone prevented nitric oxide (NO) production, and this effect was correlated with reduced levels of protein expression of the inducible form of NO synthase (iNOS). The molecular mechanism by which sauchinone inhibits iNOS gene expression appeared to involve the inhibition of NF-κB activation. Moreover, pancreatic β-cells treated with cytokines upregulated the phosphorylation of STAT-1, STAT-3 and STAT-5, however, pre-treatment with sauchinone attenuated these effects. Additionally, in a second set of experiments in which rat islets were used, the protective effects of sauchinone in rat islets were essentially the same as those observed when RINm5F cells were used. Sauchinone prevented cytokine-induced NO production, iNOS expression, JAK/STAT activation, and NF-κB activation and inhibition of glucose-stimulated insulin secretion (GSIS). Collectively, these results suggest that sauchinone can be used for the prevention of functional β-cell damage.
authors.affiliation: Zoonosis Research Center, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000633:toxicity*; D004149:Dioxoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007371:Interferon-gamma / Q000633:toxicity; D053583:Interleukin-1beta / Q000633:toxicity; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D016207:Cytokines; D004149:Dioxoles; D007328:Insulin; D053583:Interleukin-1beta; D016328:NF-kappa B; D050791:STAT Transcription Factors; C410958:sauchinone; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II