Dual anticholinesterase and antioxidant activity of selected plants used in Unani medicines and in silico studies of identified compounds from UPLC-QTOF analysis

Abstract

IntroductionCholinesterase is the enzyme responsible for the degradation of the neurotransmitter acetylcholine. Cholinesterase inhibitors are synthetic drugs that provide symptomatic relief to Alzheimer’s patients. Synthetic cholinesterase inhibitors are associated with several side effects. The current study is based on finding a suitable lead from natural products, specifically plants used in Unani medicine for various ailments. MethodsThree plants used in Unani medicine were selected and investigated for cholinesterase (acetylcholinesterase [AChE] and butyrylcholinesterase [BuChE]) inhibition, that is, Cyperus rotundus L., Delphinium denudatum Wall. ex Hook.f. & Thomson, Paeonia officinalis L. ResultsAn aqueous extract of C rotundus inhibits BuChE and AChE by 45 ± 1.54% and 15.99 ± 2.5%, respectively. An ethanolic extract exhibits 82.5 ± 2% and 65.55 ± 1.74% inhibition for BuChE and AChE, respectively. The ethanolic extract showed a mixed mode of inhibition. An aqueous extract of P officinalis showed 44.94 ± 1.29% and 29.52 ± 1.96% inhibition for BuChE and AChE, respectively. An ethanolic extract exhibits 59 ± 0.73% and 38 ± 0.005% for BuChE and AChE, respectively, with an uncompetitive inhibition mode. An aqueous and ethanolic extract of D denudatum showed 39.73 ± 1.58% and 52 ± 1.02% inhibition of BuChE, respectively, and 29.52 ± 0.75% and 43 ± 1.31% for AChE. Significant free radical scavenging activity was observed in C rotundus and P officinalis using 1,1-Diphenyl-2-picrylhydrazyl assay. Ethanolic extracts were more active and were subject to secondary metabolite analysis using UPLC-QTOF to identify abundant phytoconstituents responsible for the inhibitory activity. Individual interaction of identified phytoconstituents with target proteins was demonstrated using molecular docking analysis using Autodock 4.2. ADMET studies showed the predicted pharmacokinetic profile of the compounds.