ABSTRACT
Acetylcholinesterase (AChE) is an enzyme that is involved in the breakdown of some neurotransmitters. Its inhibition is one of the treatment strategies employed in the management Alzheimer diseases. Flavonoids isolated from the leaves of Kigelia africana were investigated for their comparative AChE inhibition. The extract of the leaves was subjected to vacuum liquid chromatography (VLC) to obtain four fractions using n-hexane (n-hex, 100%), n-hexane/dichloromethane (hex/DCM, 1:1), dichloromethane/ethyl acetate (DCM/EtOAc, 1:1) and ethyl acetate/methanol (EtOAc/MeOH, 1:1). The four fractions were subjected to AChE inhibitory study with DCM/EtOAc (1:1) fraction showing the highest inhibitory activity. Three flavonoids were isolated from this fraction and their structures were elucidated and characterised using 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) techniques. Their spectroscopic data compared well with literature. The compounds demonstrated considerable inhibition of AChE activity with luteolin (1), rutin (2) and quercetin (3) that showed IC50 of 945.0, 282.1, 254.8 μg/ml respectively as against the IC50 of 38.93 μg/ml for rivastigmine, a well-known cholinesterase inhibitor. Compound 3 showed 17.89 ± 0.57 and 7.70 ± 0.64 μ/l/mg protein at 200 and 400 μg/ml respectively, for AChE activity as against 10.37 ± 0.99 and 6.24 ± 1.24 μ/l/mg protein showed by rivastigmine at 200 and 400 μg/ml respectively. This study showed that the constituents responsible for the AChE inhibition in the crude extract as reported by Falode et al., 2017 resided in the DCM/EtOAc (1:1) fraction. The structure-activity relationship of the flavonoids revolves around substitution in position 3 of the compounds.
ABSTRACT
Antiaris africana belongs to the family Moraceae, it is commonly called “False Iroko” tree and one of the medicinal plants used in treatment of mental and nervous disorders in Nigeria. We have previously established the neuroprotective properties of crude extract of A. africana. The present study was thus designed to investigate the neuroprotective effect of different solvent fractions of A. africana against cyanide neurotoxicity in vitro. Cyanide induced a significant (P<0.01) inhibition of NADH succinate dehydrogenase, a key enzyme in mitochondria function as well as significant increase in oxidative stress as observed in the high level of malonedialdehyde (MDA), protein carbonyl (PC) and activity of monoamine oxidase (MAO) and decreased concentration of reduced glutathione (GSH) as compared to the control. Co-administration with different solvent fractions of A. africana (hexane fraction [HFA], dichloromethane fraction [DFA] and methanolic fraction [MFA]) significantly ameliorated the toxic effect of KCN as compared to the induced, untreated group (P<0.05). The results in this study showed that HFA (79.04% reversal of NSD inhibitory activity of KCN), DFA (63.68% and 72.6% activity against KCN induced LPO and PC respectively). However, MFA showed the best activity against GSH depletion caused by KCN (12.21%) and inhibition of MAO activity induced by KCN (94.63%). In conclusion, all the fractions possess neuroprotective activities at varying degrees against mitochondria damage by KCN. This result further substantiated the ethnomedicinal usage of A. africana and can provide novel compounds in the treatment of mitochondria-related neurodegenerative diseases.