Comparing immunosuppressive effects of isolates from Artocarpus Tonkinensis, a tree growing in north Vietnam, their derivatives with Cortisteroids on thymocyte apoptosis
Domenico V. Delfino
Section of Pharmacology, Toxicology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
Current treatments for immunological disorders are all empirical, using immunosuppressive drugs identified by screening large numbers of natural and synthetic compounds. The drugs currently used to suppress the immune system inhibit signalling events within T lymphocytes. These drugs are all very broad in their actions and inhibit protective functions of the immune system as well as harmful ones. Severe side effects are therefore a common complication of immunosuppressive drug therapy. The ideal immunosuppressive agent would be one that targets the specific part of the adaptive immune response that causes tissue injury. Glucocorticoids are effective therapeutic agents for treatment of autoimmune diseases based upon their anti-inflammatory, immunosuppressive, and cytolytic properties, unfortunatelly, associated with a wide array of side effects.
Natural plant products have been used throughout human history for various purposes. Having coevolved with life, these natural products are billions of years old. Tens of thousands of them are produced as secondary metabolites by the higher plants as a natural defense against diseases and infection. Medicines derived from plants have played a pivotal role in the health care of many cultures, both ancient and modern. Of the approximately 877 small-molecule drugs introduced worldwide between 1981 and 2002, most (61%) can be traced back to their origins in natural products.
The leaves of vietnamese tree Artocarpus Tonkinensis are used in the traditional medicine to cure the autoimmune disease arthritis without any side effect. Professor Tran Van Sung group of Hanoi’s VAST isolated from this plant few auronol glycosides with immunosuppressive properties (1). These compounds are tested by us to analyze biochemical pathways and to characterize new therapeutic properties.
Specifically, we standardized an experimental model suited to compare properties of the vietnamese compounds with the classical glucocorticoid drugs. The model is made by transgenic mice that overexpress GILZ, a glucocorticoid-induced gene, in the T-cell lineage, the altered function of which can trigger autoimmune diseases. We found that stimulation of these mice with IL-2, a cytokine important in the immune response, alters the ratio between helper and cytotoxic T lymphocytes and that T helper cell number is augmented in aged mice (2, contributed by MAE). Our goal is to see if natural compounds from Vietnam are able to cure the abnormalities of these mice and to dissect the biochemical pathways involved in the process.
1) Thuy TT, Kamperdick C, Ninh PT, Lien TP, Thao TTP, Sung TV. Immunosuppressive auronol glycosides from Artocarpus Tonkinensis. Pharmazie 59:297-300 (2004).
2) Pozzesi N, Gizzi S, Gori F, Vacca C, Cannarile L, Riccardi C, Delfino DV. IL-2 induces an altered CD4/CD8 ratio of splenic T lymphocytes from transgenic mice overexpressing the glucocorticoid-induced protein GILZ. J Chemother 19:562-569 (2007).