The Study On Pharmacological Mechanism Of Toosendanin

Abstract: Toosendanin, a triterpenoid derivative extracted from Melia toosendan Siebet Zucc, was demonstrated to be a selective presynaptic blocker and an effectivelyantibotulismic agent in previous studies. In recent years, it was observed that at lowconcentrations, toosendanin induced cell differentiation and apoptosis. All thesedetected pharmacological characters indicated that toosendanin is useful in bothscientific research and medical use. Here, by using patch-clamp, we studied thepharmacological mechanism of toosendanin.1. By using whole-cell patch-clamp recording, we studied the effects oftoosendanin on the Ca²⁺ channels in NG108-15 and ventricular cells. The resultsshowed that toosendanin selectively increased the L-type Ca²⁺ channel currents inNG108-15 cells in an irreversible way. The long-term effect of TSN on Ca²⁺ influx viaL-type Ca²⁺ channels was a continuous increase. The results indicated that the long-term effect of toosendanin on the L-type Ca²⁺ channels might result in intracellularCa²⁺ overload, which leads to neurotransmission blockade, cell differentiation andapoptosis. The results of a further study carried on neonatal rat ventricular cellsshowed that toosendanin facilitated L-type Ca²⁺ channels by altering the voltagesensitivity and prolonging the open time of the channels.2. By using single-channel patch-clamp recording, we studied theantibotulismic mechanism of toosendanin. Translocation of the light chain proteasethrough the heavy chain formed channel is a pivotal step in the intoxication process ofBoNT. The results showed that the channel formation was delayed and sizes of the...