Piperine: From Green Extraction to Clinical Translation-A Review
Abstract
Background: Piperine has diverse pharmacological and bioenhancing activities, but poor aqueous solubility, variable exposure, interaction liability, and discontinuity across production, formulation, and clinical evaluation limit translation. This review integrates these frequently separated stages.
Methods: A structured narrative PubMed search covered English-language studies published from 1 January 2021 to 27 April 2026, supplemented by ClinicalTrials.gov records checked through 13 June 2026, backward citation searching, and selected earlier seminal studies. Evidence was synthesized by experimental level, methodological limitations, and translational relevance.
Key findings: In one solvent-circulation study, response surface methodology optimization increased the reported piperine yield from 3.87% to 5.20% of dry material, although external batch or production-scale validation was not reported. In rats, a solid piperine self-nanoemulsifying drug delivery system produced 4.92-fold higher relative oral bioavailability than pure piperine dispersion, without human pharmacokinetic validation. Preclinical studies reported anticancer, anti-inflammatory, neuroprotective, anti-infective, and metabolic effects. Head-and-neck cancer-cell IC50 ranges were 102.8-176.0 µM in HEp-2 cells and 121.0-249.9 µM in SCC-25 cells, without exposure-matched in vivo confirmation. Published trials included COVID-19 (n=140), sepsis (n=66), and ischemic stroke (66 randomized; 56 completed); these…
How strong is the evidence?
Evidence Hub reads this as a review, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 140 participants or records.
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