Role of piperine in CNS diseases: pharmacodynamics, pharmacokinetics and drug interactions

ABSTRACT

Introduction: Piperine, the major bioactive component from black pepper, has gained increasing attention for its beneficial effects in the central nervous system (CNS). However, its related pharmacodynamics and brain pharmacokinetics, as well as its interaction with other CNS drugs are lacking, which may hinder its therapeutic and safe use.

Areas covered: The current review provides an updated summary on CNS activities of piperine, including anti-epileptic, anti-depressive and neurodegeneration protection effect. The brain pharmacokinetic properties of piperine together with the approaches to enhance its aqueous solubility were summarized. Considering the wide use of black pepper and the well-reported alteration on CYP and transporters by piperine, interactions between piperine and CNS drugs are also illustrated for the first time.

Expert opinion: Although the CNS beneficial effects of piperine have been extensively studied in preclinical models, clinical evidence on its CNS application is barely available, which may be attributed to its limited aqueous solubility, unclear pharmacokinetic properties in humans and potential toxicities during long-term use at higher doses. Although beneficial interactions between piperine and certain CNS drugs were often reported in preclinical studies, more mechanistic studies with clinically relevant doses should be conducted to provide guidance on their clinical combination use.

KEYWORDS:

• Piperine
• CNS effects
• pharmacokinetics
• pharmacodynamics
• interaction

Article highlights

• Beneficial CNS effects of piperine, including protection against seizures, depression and neurodegenerative diseases were mainly found in preclinical studies with insufficient clinical evidence.

• Potential CNS related toxicities have been observed in animals after administration of piperine at its effective dose level, suggesting that further verifications on its therapeutic index for specific CNS disease treatment and long-term use safety are necessary.

• Biopharmaceutics and pharmacokinetic characterization of piperine revealed its limited aqueous solubility, high permeability and extensive tissue bindings. Effective formulations to enhance the aqueous solubility of piperine are essential for its further drug development and clinical application.

• Although piperine may alter the pharmacokinetics of CNS drugs during their concomitant use in both animal and human, leading to potential beneficial pharmacodynamic outcomes, such beneficial interactions were not yet conclusive due to the unidentified mechanisms and the lack of investigation with clinically relevant doses.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.