Piper spices represent an inexhaustible reservoir of bioactive compounds that may act as drug leads in natural product research. The aim of this study was to investigate a series of methanolic fruit extracts obtained from P. nigrum (black, green, white and red), P. longum and P. retrofractum in comparative phytochemical and multi-directional biological (antimicrobial, antioxidant, anti-enzymatic and anti-melanogenic) assays. The metabolite profiling revealed the presence of 17 piperamides, with a total content of 247.75-591.42 mg piperine equivalents/g. Among the 22 tested microorganism strains, Piper spices were significantly active (MIC < 0.1 mg/mL) against the anaerobes Actinomyces israelii and Fusobacterium nucleatum. The antioxidant and anti-enzymatic activities were evidenced in DPPH (10.64-82.44 mg TE/g) and ABTS (14.20-77.60 mg TE/g) radical scavenging, CUPRAC (39.94-140.52 mg TE/g), FRAP (16.05-77.00 mg TE/g), chelating (0-34.80 mg EDTAE/g), anti-acetylcholinesterase (0-2.27 mg GALAE/g), anti-butyrylcholinesterase (0.60-3.11 mg GALAE/g), anti-amylase (0.62-1.11 mmol ACAE/g) and anti-glucosidase (0-1.22 mmol ACAE/g) assays. Several Piper extracts (10 μg/mL) inhibited both melanin synthesis (to 32.05-60.65% of αMSH+ cells) and release (38.06-45.78% of αMSH+ cells) in αMSH-stimulated B16F10 cells, partly explained by their tyrosinase inhibitory properties. Our study uncovers differences between Piper spices and sheds light on their potential use as nutraceuticals or cosmeceuticals for the management of different diseases linked to bacterial infections, Alzheimer's dementia, type 2 diabetes mellitus or hyperpigmentation.
Keywords: Piper; anti-melanogenic; anti-tyrosinase; antimicrobial; natural bioactive agents; piperamides.