Toxicological profile and acetylcholinesterase inhibitory potential of Palicourea deflexa, a source of β-carboline alkaloids

Palicourea genus is chemically and taxonomically close to Psychotria genus, a well-known source of neuroactive alkaloids. It has been previously reported the pharmacological potential of these alkaloids in some targets related to the neurodegenerative process. In this context, this study was carried out in order to evaluate the toxic effects and acetylcholinesterase (AChE) inhibitory potential of Palicourea deflexa fraction of total alkaloids (FTA). P. deflexa FTA was analyzed by means of HPLC-DAD and HRMS-ESI. We performed toxicological screening through Fish Embryo Toxicity (FET) test using zebrafish embryo and abnormal developmental phenotypes were recorded daily. For AChE inhibition, zebrafish brains were used as enzymatic source and formation of thiolate dianion of 5,5′-Dithiobis(2-nitrobenzoic acid) (DTNB) was used to monitor acetylthiocholine hydrolysis. Lineaweaver-Burk double reciprocal plots were used to indicate mode of inhibition. Chemical analysis of the P. deflexa FTA allowed the identification of the main compound as harman-3-carboxylic acid. This fraction was evaluated in vivo for its toxicological effect. The zebrafish embryo test indicated that the FTA has a lethal concentration of 50% (LC50) = 72.18 μg/mL. Further, the FTA was evaluated for its AChE inhibitory profile, demonstrating an inhibitory concentration of 50% (IC50) of 50.65 μg/mL. Lineaweaver-Burk double reciprocal plots indicated a mixed mode of inhibition. It is reported for the first time the toxicological and pharmacological profile of the alkaloid fraction of Palicourea deflexa in zebrafish models.