In vitro inhibition of acetylcholinesterase by Brazilian plant extracts from Rubiaceae family

The neurotransmitter acetylcholine (ACh) plays a central role in the regulation of physiological functions related to the Central and Peripheral Nervous System. The inhibition of acetylcholinesterase (AChE), the major enzyme involved in the breakdown of ACh, is recognized as one of the most promising strategy for the treatment of human and veterinary cholinergic system-related disorders, such as Alzheimer, Myasthenia gravis, Botulism, Tick paralysis, and others. Despite the relevance, there is a lack of AChE inhibitors approved for clinical use, the current drugs have limitations of efficacy, short half-lives and/or unfavorable side effects. Brazilian flora represents an outstanding source for the discovery of bioactive molecules, which prompted us to screen plants belonging to the Rubiaceae family for their AChE inhibitory activity (AChEI). Twenty-eight species collected in a Atlantic forest fragment in the southeastern Brazil were dehydrated (45^oC), milled (0.05 mm particle size) and extracted by maceration (methanol, 72h). Extract solutions were concentrated to dryness and properly subjected to qualitative [1] and quantitative [2] AChEI assays. Based on this approach, 17 species showed some AChEI activity, while 2 samples were considered as potent AChE inhibitors [3]. Phytochemical characterization is still in progress and suggests the occurrence of alkaloids as the main bioactive compounds in such plant extracts from Rubiaceae family. These findings reinforce the high potential for the discovery of new bioactive compounds useful for some cholinesterase disorders.

[1] A Marston, J Kissling, K Hostettmann. Phytochem An 2002; 13: 51 – 54

[2] IK Rhee, MV Meent, K Ingkaninan, R Verpoorte, M Okada, M Marimo Heterocycles 1997; 45: 2253 – 2260

[3] B Vinutha, D Prashanth, K Salma, SL Sreeja, D Pratiti, R Padmaja, S Radhika, A Amit, K Venkateshwarlu, M Deepak J Ethnopharmacol 2007; 109: 359 – 363