Piperine

Piperine is the primary pungent alkaloid found in black pepper (Piper nigrum) and long pepper (Piper longum) (Wikipedia, 2024). Although it is a bioactive small molecule rather than a biological target, it is of significant pharmacological interest due to its interactions with several key proteins in the human body (NIH, 2018). Its most notable role is as a bioavailability enhancer, achieved through the potent inhibition of metabolic enzymes like Cytochrome P450 3A4 (CYP3A4) and efflux transporters such as P-glycoprotein (ABCB1), which increases the systemic exposure of various drugs and nutrients (ResearchGate, 2026; NIH, 2023). Piperine also acts as an agonist for the Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel, contributing to its effects on thermogenesis and pain sensation (NIH, 2005; BOC Sciences, 2024). Additionally, it exhibits anti-inflammatory, antioxidant, and anti-tumor properties by modulating signaling pathways such as NF-κB and STAT3 (NIH, 2018; ResearchGate, 2019). While frequently used as a dietary supplement adjuvant, its ability to alter the pharmacokinetics of other medications necessitates careful consideration of potential drug-drug interactions (NCATS, 2024). It has also been shown to modulate GABAA receptors, suggesting potential neuroprotective and sedative effects (NIH, 2011). Research continues to explore its potential in treating metabolic disorders like obesity and chronic inflammatory conditions (NIH, 2023).

Other names

1-PiperoylpiperidineBioperine(2E,4E)-5-(1,3-Benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one

Piperine acts as an agonist of the Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel and a modulator of GABAA receptors (NIH, 2011; BOC Sciences, 2024). It also functions as a potent inhibitor of the metabolic enzyme Cytochrome P450 3A4 (CYP3A4) and the efflux transporter P-glycoprotein (ABCB1), which accounts for its role as a bioavailability enhancer (ResearchGate, 2026; MedChemExpress, 2024).