Exp Mol Med.  2010 Sep;42(9):628-638. 10.3858/emm.2010.42.9.062.

Sulfuretin protects against cytokine-induced beta-cell damage and prevents streptozotocin-induced diabetes

• Song MY
• Jeong GS
• Kwon KB
• Ka SO
• Jang HY
• Park JW
• Kim YC
• Park BH

• KMID: 983955
• DOI: http://doi.org/10.3858/emm.2010.42.9.062

Abstract

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-1beta and IFN-gamma to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-kappaB 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.

Keyword

cytokines; diabetes mellitus, experimental; NF-kappaB; Rhus verniciflua; streptozotocin; sulfuretin

MeSH Terms

Animals
Benzofurans/*pharmacology/therapeutic use
Cell Line
Cytokines/*adverse effects
Diabetes Mellitus, Experimental/drug therapy/*prevention & control
Flavonoids/pharmacology/therapeutic use
Hypoglycemic Agents/pharmacology/therapeutic use
Insulin-Secreting Cells/*drug effects
Male
Mice
Mice, Inbred ICR
NF-kappa B/*metabolism
Rats
Rats, Sprague-Dawley
Rhus/chemistry