Involvement of estrogen receptors in silibinin protection of pancreatic β-cells from TNFα- or IL-1β-induced cytotoxicity

Silibinin is a polyphenolic flavonoid that exhibits anticarcinogenic, anti-inflammatory and cytoprotective effects. The effect of silibinin on pancreatic islet beta-cell is yet largely unknown in spite of well documented-hepatoprotective effects. Protecting the functional insulin-producing beta-cells in the pancreas is a major therapeutic challenge in the patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). This study reports the effect of silibinin on the rat pancreatic beta-cell line, INS-1, damaged with pro-inflammatory cytokine, TNF alpha or IL-1 beta. Exposure to TNF alpha or IL-1 beta for 48 h caused INS-1 cells to reduce the production of insulin as well as cell viability. These actions of TNF alpha or IL-1 beta are associated with suppression of the expression of estrogen receptors (ERs). Further study revealed that silibinin protected the suppression in the expression of both ER alpha and ER beta that were involved in insulin synthesis and release, respectively. Furthermore, evidence is obtained that silibinin may impede the loss of critical INS-1 cells by promoting autophagy and preventing apoptosis. Direct cytoprotective effects of silibinin on INS-1 cells suggest that silibinin may be therapeutically beneficial for diabetes.