Cortex cinnamomi extract prevents streptozoticin- and cytokine-induced β-cell damage by inhibiting NF-κB

AIM: To clarify the mechanism underlying the antidiabetic activities of cortex cinnamomi extract (CCE). METHODS: To induce in vivo diabetes, mice were injected with streptozotocin (STZ) via a tail vein (100 mg STZ/kg body weight). To determine the effects of CCE, mice were administered CCE twice daily for 7 d by oral gavage starting 1 wk before the STZ injection. Blood glucose and plasma insulin concentration were measured as an index of diabetes. Also, to induce cytotoxicity of RINm5F cells, we treated with cytokines (IL-1 beta (2.0 ng/mL) and IFN-gamma (100 U/mL)). Cell viability and nitric oxide production were measured colorimetrically. Inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. The activation of NF-kappa B was assayed by using gel mobility shift assays of nuclear extracts. RESULTS: Treatment of mice with STZ resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of STZ were completely prevented when mice were pretreated with CCE. The inhibitory effect of CCE on STZ-induced hyperglycemia was mediated through the suppression of NOS expression. In rat insulinoma RINm5F cells, CCE completely protected against interleukin-1 beta and interferon-gamma-mediated cytotoxicity. Moreover, RINm5F cells incubated with CCE showed significant reductions in interleukin-1 beta and interferon-gamma-induced nitric oxide production and in iNOS mRNA and protein expression, and these findings correlated well with in vivo observations. CONCLUSION: The molecular mechanism by which CCE inhibits NOS gene expression appears to involve the inhibition of NF-kappa B activation. These results reveal the possible therapeutic value of CCE for the prevention of diabetes mellitus progression. (C) 2006 The WJG Press. All rights reserved.