Rauvolfia ligustrina: abordagem fitoquímica das raízes e avaliação farmacológica dos alcaloides isolados

Abstract

Chemical exploration of Rauvolfia ligustrina (Apocynaceae) roots led to the isolation of 19 indole alkaloids of different classes, four of which are yohimbinics: yohimbine acid (RL6), α-yohimbine (RL8), 18-β-hydroxy-3-epi-α -yohimbine (RL11) and corynanthine (RL12); two heteroiohimbinics: aricin (RL9) and isoreserpyline (RL10); an ajmaline: raucafricine (RL5); three sarpagan: 21(R)-(O-β-glycosyl)-hydroxy-sarpagin-17-oic acid (RL7), sarpagine (RL13) and 3-hydroxysarpagine (RL16); three reserpinics: reserpine (RL1), deserpidine (RL3) and isoreserpine (RL4); four peraksinics: rauvovertin B (RL14/15) and peraksine (RL17/18); an aoxindolic: isocarapanaubin (RL2); and a bisindole: sarpaginine (RL19). It is worth to say that RL7 and RL19 are being reported for the first time. The alkaloids were isolated by gravitational chromatography using Sephadex LH20, silica gel or high efficiency liquid silica (HPLC) columns, with their specific structures using ¹H and ¹³C NMR methods (1D and 2D) and high-resolution mass spectrometry resolution (EMAR). RL1 to RL12 alkaloids were assayed in the nodrenergic transmission test, in which RL7 had the highest inhibition potential followed by RL1 and RL6. Interestingly, RL2 and RL12 alkaloids showed a potent inverse effect. The alkaloids RL13 to RL19 were tested for anxiolytic activity in zebrafish, which revealed that the alkaloids RL13, RL14/15, RL17/18 and RL19 have a high anxiolytic potential. The mechanisms of action of the compounds were determined by a molecular docking study, which showed that RL13, RL14/15, RL17/18 act via the GABAergic pathway and that RL19 via the serotonergic pathway.