Piperine from pepper— a spice that enhances other medicines and herbs?

Aim of the study: Piperine, a bioactive compound from Piper nigrum and Piper longum, has shown promising activity as an efflux pump (EP) inhibitor and as an adjunct in the treatment of tuberculosis (TB). This systematic review examined scientific studies on the activity of piperine against mycobacteria, focusing on its mechanism of action, drug interactions, and antimycobacterial activity.

Results: After duplicate publications were removed, 208 publications remained. Of these, we evaluated the full text of 13 articles. After applying the inclusion criteria, eight studies were included in this systematic review. The results showed that piperine has promising anti-TB activity, mainly when combined with antimicrobials, and plays an important role as an EP inhibitor.

Aim of the study: The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilized because of its poor bioavailability, caused by its rapid metabolism in the liver and intestinal wall.

Results: Time to maximum concentration increased significantly (P < 0.02), while elimination half-life and clearance decreased significantly (P < 0.02), and bioavailability increased by 154%. In humans, after a dose of 2 g of curcumin alone, serum levels were either undetectable or very low. Taking 20 mg of piperine at the same time produced much higher concentrations from 0.25 to 1 h after administration (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h); the increase in bioavailability was 2000%. The study shows that, at the dosages used, piperine enhances the serum concentration, extent of absorption, and bioavailability of curcumin in both rats and humans, with no adverse effects.

Aim of the study: Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options because of its aggressive nature, high recurrence rate, and resistance to conventional therapies. Piperine, a bioactive compound in black pepper, crosses the blood-brain barrier (BBB) and has anticancer effects.

Results: MAOB is significantly overexpressed in GBM and is associated with a poor patient prognosis. Piperine effectively reduced MAOB levels, induced selective cytotoxicity in glioma cells, modulated oxidative stress through NRF2 upregulation, and enhanced the DNA damage response. Co-treatment with piperine and TMZ significantly increased cytotoxicity and DNA damage. Piperine has anti-GBM effects by targeting MAOB, disrupting ROS homeostasis, and inducing DNA damage. It also enhances TMZ efficacy, highlighting its potential as an adjuvant therapy for GBM.

Aim of the study: To overcome the poor water solubility of icaritin (ICT) and piperine (PIP), which limits their therapeutic potential, a co-amorphous drug delivery system was developed.

Results: The ICT-PIP co-amorphous system showed significantly improved solubility (3.5-fold for ICT and 3.7-fold for PIP) and intrinsic dissolution rate (2.0-fold for ICT and 1.8-fold for PIP) compared with crystalline forms. PXRD confirmed complete amorphization, with no detectable crystalline peaks; FT-IR revealed intermolecular hydrogen-bonding interactions between ICT and PIP; and DSC showed a single glass transition temperature (Tg) of 164.6 °C, confirming the formation of a single-phase amorphous system. Pharmacokinetic studies found 1.6-fold and 1.4-fold increases in oral bioavailability for ICT and PIP, respectively. The system maintained excellent physical stability for six months under storage conditions. This study successfully developed a stable ICT-PIP co-amorphous system with superior solubility and bioavailability, demonstrating that co-amorphization is a viable strategy for optimizing the delivery of poorly soluble drug combinations.