Detection of novel therapeutic agents from natural resources and to study their intervention in biomedical research are highly important. Piper species are of prime importance in commerce, economy and in a variety of ayurvedic applications. We investigated on a variety of bioactivities, viz. anti-alzheimer's, anti-malarial, anti-diabetic and antioxidant potentialities of 70% hydro-methanolic extracts of edible parts (leaf, stem and fruit) of four species of Piper, namely, P. retrofractum, P. longum, P. nigrum, indigenous to West Bengal and P. betle var. Tympew indigenous to Meghalaya, India. Leaves of P. betle var. Tympew showed very high activity both in Acetylcholinesterase inhibition, (IC50 = 0.284 mg/mL +/- 0.025) and alpha glucosidase inhibition (IC50 = 0.049 mg/mL +/- 0.003). In alpha amylase inhibition, the leaves of P. longum showed the highest inhibitory activity with an IC50 value of 2 mg/mL +/- 0.257. Fruits of P. longum showed highest activity in anti-malarial activity with IC50 value of 1.624 mg/mL +/- 0.027. The metabolomic variabilities of these plant parts and species using GC/MS assisted metabolomic tool were also determined and chemometrically we discriminated these species on the basis of their metabolome profiling. Quantification of piperine content of the plant parts were done using HPTLC. All the extracts showed significant anti-cholinesterase, anti-glycosidase, anti-malarial and antioxidant activities in a dose dependant manner. The bioactivities were compared with the standard drugs and in silico analysis established their efficacy as an alternative to synthetic drugs. Several metabolites detected via GC/MS showed strong anti-cholinesterase, anti-amylase, anti-glucosidase as well as anti-malarial activities.
