Atividade Farmacológica Geral e Específica do Extrato Aquoso e da Fração Butanólica de Quassia amara L. (Simaroubaceae) e Efeito dos Compostos Isolados nas P-ATPases de Mamíferos H+.K+-ATPase e Ca2+-ATPase

Abstract

Quassia amara L. (Simaroubaceae) is a small tree, widely distributed in the Amazon, known as ―pau-amargo‖. The tea from its leaves and bark are used in popular medicine for gastric disorders and malaria. β-carboline and indolic alkaloids, steroids and quassinoids (quassin and neoquassin) were isolated from this plant and evaluated in animal models of malaria with promising results, but still preliminary. Previous pharmacological studies performed with non-standardized apolar extracts, reported sedative, analgesic, anti-inflammatory, emollient and anti-ulcer activities. In view of the reputation of Q. amara in folk medicine and scarce consistent results in the scientific literature, this work studied the systemic actions of the standardized extracts from the native plant collected in the region of Manaus. Semi-purified extracts and high purity fractions were obtained from the chemical standardization and were used to study the mechanisms of actions detected experimentally. In these studies, the popular use of Q. amara in malaria led us also to investigate the pharmacological actions of its extracts and purified fractions in mammalian P-ATPases (H+-K+-ATPase and Ca+2-ATPase) that have high structural homology with isoenzymes essential to the Plasmodium survival. The standardized extract was obtained by the partition of Q. amara AE in buthanol originating the buthanolic fraction (BuF) with the same pharmacological activity and fivefold more concentrated than AE. The purification of BuF by high performance liquid chromatography (HPLC) yielded 18 high purity fractions (F1 to F18), still in identification process. The pharmacological screening of AE and BuF did show remarkable action in the CNS. AE showed anti-inflammatory effect, apparently associated with the inhibition of pro-inflammatory mediators histamine and serotonin, but no analgesic action was observed. AE increased gastrointestinal motility and inhibited the gastric ulcers induced by stress and ethanol. BuF at tenfold lower doses inhibited the secretion and gastric acidity in vivo and the intermediate dose inhibited the total acidity stimulated by histamine, but did not when induced by bethanechol (muscarinic agonist), indicating a possible selective action in the histamine/cAMP pathway. The BuF and fractions isolated by HPLC F10, F14 and F15 potentiated the direct elicited twitches in the rat diaphragm muscle. In the Ca+2-ATPase isolated from skeletal muscle, the BuF and fractions F05, F06, F08, F09, F10, F13, F14, F15,F16 inhibited its activity and this effect may explain the potentiation of the diaphragm contraction. The FBut and fractions F11, F12, F13 and F16 inhibited the H+-K+-ATPase activity from the gastric mucosa in vitro; this effect may explain the anti-secretory and anti-ulcer activity observed in vivo, effects related to the mainly popular use of Q. amara.