Bioactive metabolites from Grindelia chiloensis with anticholinesterase activity

MUSSO, FLORENCIA; CAVALLARO, VALERIA; RODRIGUEZ, SILVANA; BISCUSSI, BRUNELLA; DONOZO, MARTINA; ANA PAULA MURRAY

Bahía Blanca

Congreso; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental.; 2024

Asociación Argentina de Farmacología Experimental

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases among the elderly, characterized by a progressive decline in memory, which impairs patients' cognitive abilities. AD is a complex and multifactorial disorder, and one of the most prominent theories regarding its etiology is the cholinergic hypothesis. This hypothesis is based on the degeneration of cholinergic neurons and the deficiency of the neurotransmitter acetylcholine (ACh). It has been demonstrated that ACh is hydrolyzed by the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Therefore, current pharmacological treatments aim to increase ACh levels in the brain using enzyme inhibitors such as rivastigmine, donepezil, and galantamine, resulting in improved nerve transmission and reduced disease symptoms.Given this background and the various adverse effects associated with the drugs mentioned, natural alternatives for AD treatment, such as the use of medicinal plants, are being explored. In previous studies conducted by our research group, the ethanolic extract (EE) of the plant species Grindelia chiloensis (Cornel.) Cabrera showed significant inhibitory activity against AChE and BChE enzymes (IC50 of 960 μg/mL for AChE and 372 μg/mL for BChE). To isolate the bioactive metabolites, the EE was partitioned using solvents of different polarities, resulting in three subextracts: dichloromethane (DS), n-butanolic (nBS), and aqueous (AS). Of these, DS exhibited the highest inhibitory activity against the enzymes (AChE inhibition: 54% at 0.5 mg/mL; BuChE inhibition: 60% at 0.5 mg/mL). Fractionation of DS by column chromatography led to the isolation of several labdane-type diterpenes, among which grindelic acid and 6-oxogrindelic acid, both previously reported in other species of the same genus, were identified as major components. The identification of other compounds isolated from DS, as well as the bioactivity of each of them, will be presented.