Sulfuretin protects against cytokine-induced beta-cell damage and prevents streptozotocin-induced diabetes.
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.
Song
Mi-Young
MY
Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju 561-756, Korea.
Jeong
Gil-Saeng
GS
Kwon
Kang-Beom
KB
Ka
Sun-O
SO
Jang
Hyun-Young
HY
Park
Jin-Woo
JW
Kim
Youn-Chul
YC
Park
Byung-Hyun
BH
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D016207:Cytokines / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000517:prevention & control*; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029045:Rhus / Q000737:chemistry
D001572:Benzofurans; D016207:Cytokines; D005419:Flavonoids; D007004:Hypoglycemic Agents; D016328:NF-kappa B; C054989:sulfuretin