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Herbs have long been esteemed for their therapeutic properties and utilized to treat a broad spectrum of diseases. Notably, piperine is a naturally occurring alkaloid abundantly found in numerous plants, with four isomeric variants. Contemporary literature revealed that piperine has significant pharmacological activities, including cardioprotective, neuroprotective, gastroprotective, hepatoprotective, nephroprotective, anti-allergic, anti-cancer, anti-inflammatory, anti-diabetic, anti-microbial, and many more. Piperine's diverse pharmacological profile not only reveals its versatility in experimental studies but also highlights its effectiveness in numerous clinical outcomes. However, despite the therapeutic benefits evident from numerous animal and human investigations, the clinical relevance of piperine faces numerous challenges because of its low aqueous solubility, stability, and limited bioavailability. To address these constraints, nanoformulations like nanoparticles, liposomes, micelles, gold nanogels, nanosuspensions, nanoemulsions, and self-nanoemulsifying drug delivery systems have emerged as innovative approaches that play a crucial role in optimizing the bioavailability and efficacy of piperine. By utilizing these novel drug delivery systems, piperine’s therapeutic potential can be harnessed, paving the way for its application in diverse clinical conditions. This manuscript seeks to advance the current understanding of piperine's therapeutic potential, elucidating its mechanistic insights against numerous disorders and exploring various nanoformulation strategies to optimize its delivery and efficacy.
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