Antioxidant and acetylcholinesterase inhibitory activities, in silico analyses, and anti-Alzheimer's disease potential of leaf extracts of three Nigerian endemic medicinal plants (Spondias mombin, Carica papaya and Kalanchoe crenata)

Background The evaluation of the correlations between antioxidant and anti-acetylcholinesterase activities of methanol leaf extracts of three Nigerian endemic plants, Spondias mombin, Carica papaya and Kalanchoe crenata, was carried out. Their constituent phytochemicals were identified by HPLC-DAD fingerprinting. The antioxidant activity as typified by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2 '-azino-bis-(3-ethylbenthiazoline-6-sulfonic acid (ABTS(+)) and nitric oxide (NO) scavenging activities were evaluated. The acetylcholinesterase (AChE) inhibitory activity of the extracts was also determined. Results The extracts contained appreciable amounts of the flavonoids, quercetin and kaempferol. The extracts of Spondias mombin, Carica papaya and Kalanchoe crenata showed concentration-dependent inhibitory activities against DPPH and ABTS(+) with IC50 of 43.29 +/- 0.443 mu g/mL, 59.27 +/- 0.644 mu g/mL and 80.20 +/- 0.414 mu g/mL; 25.43 +/- 0.325 (mu g/mL), 39.84 +/- 0.163 mu g/mL and 59.02 +/- 0.376 (mu g/mL), respectively. The IC50 for the NO scavenging activities of the Spondias mombin, Carica papaya and Kalanchoe crenata extracts were 41.99 +/- 0.217 mu g/mL, 50.44 +/- 0.281 mu g/mL and 60.12 +/- 0.512 mu g/mL, respectively. The IC50 for the inhibitory effects on AChE was 53.24 +/- 0.327 mu g/mL, 60.95 +/- 0.290 mu g/m and 70.5 +/- 0.426 mu g/mL, respectively. The effectiveness of the plant in all the experimental tests was in the following order: S. mombin > C. papaya > K. crenata. The total flavonoid and total phenolic contents have extremely significant positive correlations with the antioxidant activities and AChE inhibitory activity. The correlation coefficients (r(2)) of DPPH scavenging activity and NO scavenging activity with the AChE inhibitory activity were 0.8295 mu g/mL and 0.7337 mu g/mL, respectively (P < 0.0001). The molecular docking and pharmacokinetic analyses on some constituent phytochemicals showed that quercetin, kaempferol, ferulic acid, leucocyanidin, gallic acid and isorhamnetin fulfilled the requirements for an anti-Alzheimer drug. Conclusions The results suggest that the plant species provide a significant source of secondary metabolites that can act as natural antioxidants and acetylcholinesterase inhibitors, which will be helpful in the treatment of Alzheimer's disease.