Issue Archive

The fact that the fruit and bark of plant belonging to family Melia could be used as digestive tract-parasiticide and agriculturalinsecticide was recorded about two thousand years ago in ancient China. Toosendanin (TSN, C30H38O11, FW=574), a triterpenoidderivative, was extracted from the bark of Melia toosendan Sieb. et Zucc. by Chinese scientists in 1950’s and used as an ascarifuge inChina instead of imported sendanin. Studies have demonstrated that TSN possesses special biological actions as well as considerablevarious values in scientific research, clinic medicine and agriculture. The first is that by interfering with neurotransmitter release bycausing an initial facilitation, TSN eventually blocks synaptic transmission at both the neuromuscular junction and central synapses.The action might result from TSN-induced Ca2+-sensitivity change and final elimination of transmitter release machinery. The secondis that despite sharing many similar actions with botulinum neurotoxin (BoNT) on blocking neuromuscular transmission, TSN has amarkedly antibotulismic action in vivo and in vitro: TSN-treatment saves the botulism mice or monkeys from death; TSN-incubationin vitro or TSN-injection in vivo endows neuromuscular junction with a high tolerance to BoNT. Studies suggest that the antibotulismicaction is achieved by preventing BoNT from approaching its enzymatic substrate, SNARE protein. The third, in recent years, it is alsoobserved that TSN can induce differentiation and apoptosis in several cell lines, and suppress proliferation of various human cancer cells. The TSN-induced differentiation is Ca2+-dependent and the mitochondria-dependent apoptosis pathway is involved in the TSN-inducedapoptosis. The fourth is that TSN inhibits various K+ channels and selectively facilitates Ca2+ current through L-type Ca2+ channels andhence elevates [Ca2+]i. The TSN-induced [Ca2+]i increase and overload could be responsible for the TSN-induced biphasic effect onneurotransmitter release, cell differentiation, apoptosis as well as the cytotoxicity of TSN.