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

Abstract

NF-κB activation has been implicated as a key signaling mechanism for pancreatic β-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-κB pathway. Therefore, we isolated sulfuretin from Rhus verniciflua and evaluated if sulfuretin could inhibit cytokine-or streptozotocin-induced β-cell damage. Rat insulinoma RINm5F cells and isolated rat islets were treated with IL-1β and IFN-γ to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-κB 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-κB activation. Collectively, these results indicate that sulfuretin may have therapeutic value in preventing β-cell damage.

Plants and Natural Compounds with Antidiabetic Action

“…inhibit cytokine-or streptozotocin-induced damage in rat insulinoma β-cells and in isolated cells that induced toxicity (Song et al, 2010).…”

“…It is normally held in its inactive form by being bound to the inhibitory IκB molecule. However, it may be activated if IκB undergoes phosphorylation by I-Kappa-B kinase (IKK), leading to the release and activation of NF-κB that may induce pancreatic β-cell damage (Song et al, 2010;Stumvoll et al, 2005). The activation of the nuclear factor NF-κB by stress factors (cytokine molecules and free radicals) is strongly connected to β-cell damage.…”

Butein is a novel anti-adipogenic compound

“…Sulfuretin has anti-platelet, anti-mutagenic, and anti-infl ammatory effects. Recent studies have demonstrated that sulfuretin blocks the infl ammatory response in type 1 diabetes and allergic airway infl ammation models by suppressing the nuclear factor-B pathway ( 35,36 ). Fisetin is common in various vegetables and fruits, including RVS.…”

Aqueous Extracts of Liriope platyphylla Are Tightly-Regulated by Insulin Secretion from Pancreatic Islets and by Increased Glucose Uptake through Glucose Transporters Expressed in Liver Hepatocytes

“…In another study, a homoisofl avoneenriched fraction with an insulin sensitizing effect was initially extracted from L. platyphylla with 70% ethanol and sequentially separated with Diaion HP-20 and silica gel column chromatography (Choi et al, 2004). Sulfuretin, one of the main fl avonoids of Rhus vernicilua, can completely prevent the hyperglycemia and hypoinsulinemia induced by streptozotocin (Song et al, 2010). Especially, some aqueous extracts display anti-diabetic activity.…”