The Effect of Lupane Triterpenoids (Dipteryx alata Vogel) in the in vitro Neuromuscular Blockade and Myotoxicity of two Snake Venoms

Abstract

Traditional medicine of Brazilian central savannah preconizes Dipteryx alata extracts against snakebites venoms. Previous studies have shown the extract of this plant's bark antagonizing the neuromuscular blockade caused by snake venom in isolated mice diaphragm and phrenic nerve models. In the present study, the triterpenoids lupeol, lupenone, 28-OH-lupenone and betulin, which are constituents of the plant, were observed by using in vitro pharmacological tests. These tests showed the efficacy of all tested triterpenoids (1 mg/5mL) against the irreversible neuromuscular blockade caused by snake venom from Bothrops jararacussu (Bjssu, 40 µg/mL, n=19), as following: betulin (68 ± 7%, n=11) ~ lupeol (70 ± 8%, n=5) > lupenone (45 ± 9%, n=7) ~ 28-OH-lupenone (54 ± 5%, n=4). Betulin (39.5 ± 9%, n=9) and lupenone (49.5 ± 8%, n=4) significantly protected against Crotalus durissus terrificus (CDT, 10 µg/mL, n=10) envenomation of neuromuscular junction. The mixture of betulin or lupeol + Bjssu venom and betulin or lupenone + CDT venom showed significant phytochemical protection in morphological analysis. Considering both pharmacological and morphological results, betulin showed the best protective effect against neuromuscular blockade and myotoxicity caused by both snake venoms. In addition, it has a potent short-term excitatory action in the neuromuscular junction. We concluded that the studied triterpenoids, especially betulin, showed antiophidian properties. (AU)