Emodin isolated from Rheum palmatum prevents cytokine-induced β-cell damage and the development of type 1 diabetes

• Emodin inhibited the NF-κB-iNOS-NO axis through the suppression of IKK.
• Emodin prevented cytokine-induced apoptotic β-cell death.
• Emodin prevented MLDS-mediated induction of type 1 diabetes development.

Emodin is an anthraquinone derivative from rhubarb and buckthorn, and is also produced by many species of fungi. Although its anti-diabetic effect in type 2 diabetes has been reported, the potential effects of emodin on type 1 diabetes remain unclear. Therefore, in this study, we isolated emodin from rhubarb (Rheum palmatum) and investigated its effects on cytokine- or streptozotocin-induced β-cell damage and dysfunction. Emodin protected RINm5F cells or mouse islets against cytokine-induced damage by suppressing inducible nitric oxide synthase expression and nitric oxide production. The cytoprotective potential of emodin was associated with the inhibition of NF-κB signaling by reducing IκB kinase activity. The protective effects of emodin were further demonstrated by normalizing insulin secretion of cytokine-treated islets in response to glucose. In multiple low-dose streptozotocin-induced diabetes model, emodin-pretreated mice were fully resistant to the development of diabetes with normal islet morphology and insulin secretion. Immunohistochemical analysis revealed that emodin significantly decreased the number of TUNEL-positive and nuclear p65-positive pancreatic islets. These results suggest that emodin blocks the NF-κB pathway, thus protecting β-cells against diabetogenic insults. Emodin may have therapeutic value in preventing the development of type 1 diabetes by delaying the process of insulitis and by protecting against β-cell damage.