NF-kappaB activation has been implicated as a key signaling mechanism for pancreatic beta-cell damage.
Sulfuretin is one of the main
flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the
NF-kappaB pathway. Therefore, we isolated
sulfuretin from Rhus verniciflua and evaluated if
sulfuretin could inhibit
cytokine- or
streptozotocin-induced beta-cell damage. Rat
insulinoma RINm5F cells and isolated rat islets were treated with
IL-1 beta and IFN-gamma to induce cytotoxicity. Incubation of cells and islets with
sulfuretin resulted in a significant reduction of
cytokine-induced NF-gamma B activation and its downstream events, iNOS expression, and
nitric oxide production. The cytotoxic effects of
cytokines were completely abolished when cells or islets were pretreated with
sulfuretin. The protective effect of
sulfuretin was further demonstrated by normal insulin secretion of
cytokine-treated islets in response to
glucose. Treatment of mice with
streptozotocin resulted in
hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of
streptozotocin were completely prevented when mice were pretreated with
sulfuretin. The anti-diabetogenic effects of
sulfuretin were also mediated by suppression of
NF-kappaB activation. Collectively, these results indicate that
sulfuretin may have therapeutic value in preventing beta-cell damage.