Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells
Fig 6
Potential mechanism of action of bergenin in suppressing cytokine-induced apoptosis in INS-1E cells.
Proinflammatory cytokines (IL-1β, INF-γ, and TNF-α) initiate a cascade of signaling pathways leading to beta cell apoptosis. These cytokines stimulate JAK-STAT, NFκB, and MAPK pathways, which later induce intrinsic apoptotic pathway in beta cells. IL-1β also induces nitric oxide (NO) production, which causes inhibition of electron transport chain, increase in ROS production, decrease in glucose oxidation rate resulting in reduced ATP generation, and insulin production. Bergenin protected pancreatic beta cells through multiple mechanisms simultaneously. Bergenin suppressed beta cell apoptosis by potentially influencing NF-κB, MAPK and JAK/STAT pathways (represented by blue dashed lines). This is evident from the inhibition of downstream effector molecules (caspse-3, NO, ROS, and apoptosis) targeted in cell-based assays (represented by red dashed lines). By inhibiting cytokine-induced NO production, bergenin was able to increase in cellular ATP levels, decreased ROS production, and increased insulin production.