Protective effects of plant components against cytokine-induced pancreatic beta-cell dysfunction and death and exploration of the underlying mechanisms

Juvenile or type 1 diabetes is the result of the destruction of insulin-producing pancreatic beta cells by an abnormal immune reaction. We still have a limited understanding of the mechanisms leading to such destructive process, which has been so far impossible to be antagonized, due to the lack of effective and safe drugs. However, we know that protein factors, named cytokines, released by abnormally activated immune and inflammatory cells, are involved in the outcome of cell injury. On the basis of promising preliminary results, this project has the following aims: a) to assess the protective action of the extract of St. John’s wort, a herbaceous plant commonly used in phytotherapy as antidepressant, as well as of its component hyperforin, against cytokine-induced beta-cell damage; b) to clarify the mechanisms of their protective action; c) to establish their ability to attenuate the aggressivity of the immune cells. The beneficial effects of these vegetal compounds will be studied not only in cultured cells but also in rat and human pancreatic beta cells, in view of future clinical use. We will investigate by molecular biology techniques the capacity of these compounds to inhibit cytokine-activated pathways in both immune and target cells, so that dysfunction and death of insulin-producing cells could be effectively tackled. In vivo experiments will test whether these natural compounds, which are considered safe after their use in the treatment of depression, can prevent or delay the development of type 1 diabetes in laboratory animals. This study holds considerable promise to lead to the identification and characterization of new potential safe drugs of vegetal origin, capable of reducing immune reactions and preserving beta-cell function and integrity. These findings would be clinically relevant to the prevention of type 1 diabetes, the reduction of its severity and the protection of beta cells following transplantation in diabetic patients.