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
The present study aims to evaluate the protective effect of methanolic leaf extract and flavonoid-rich leaf extract ofSynsepalum dulcificum on lead-acetate-induced toxicity in Wistar albino rats. Forty-five animals were distributed intonine groups with five animals apiece. Group 1 served as the control and was given only distilled water throughoutthe course of the study. Group 2 served as the lead-induced group and was administered 50 mg/kg lead-acetate.Groups 3–8 were co-administered 50 mg/kg lead-acetate and various doses of the extracts. Group 9 was administered40 mg/kg vitamin C in addition to 50 mg/kg lead-acetate. The study lasted for 14 days. Standard procedures were usedto evaluate the hematological indices, serum total protein, urea, creatinine, as well as marker enzymes in liver andkidney of the animals. Malondialdehyde levels, superoxide dismutase, and glutathione-s-transferase activities werealso estimated in the tissues. The results showed that the extracts, especially the high doses, significantly (p < 0.05)ameliorated the harmful effects of lead administration in the liver and kidney as well as in the hematological indices.The extract could, therefore, be considered as having protective effect on lead-induced toxicity in Wistar albino rats