# Nano-formulated pomegranate extracts with dual cytotoxic and antimicrobial activity: molecular docking and mechanistic insights into leukemia cell targeting

## TL;DR

Nano-formulated pomegranate peel extract shows strong cancer cell-killing and antibacterial effects, with improved effectiveness due to better delivery and impact on cell death pathways.

## Contribution

A nano-formulated pomegranate peel extract with enhanced dual cytotoxic and antimicrobial activity is introduced, along with mechanistic insights into its action on leukemia cells.

## Key findings

- Nano-encapsulation increased the extract's cytotoxic efficacy, reducing the IC₅₀ from 1.48 µg/mL to 0.19 µg/mL.
- The nano-formulated extract induced apoptosis and cell cycle arrest in THP-1 leukemia cells.
- n-PPE-EA downregulated BCL2, PI3K, and CDK8 gene expression, suggesting modulation of key cancer pathways.

## Abstract

Punica granatum (pomegranate) peel is traditionally used for its antimicrobial and health-promoting properties in several cultures. Rich in polyphenols, the peel has attracted interest for its potential applications in treating infections and cancer, particularly in integrative approaches for immunocompromised patients.

Pomegranate peel extracts were prepared using solvents of increasing polarity, with emphasis on the ethyl acetate fraction (PPE-EA). A nano-formulated version (n-PPE-EA) was developed using a standard nano-encapsulation technique. Cytotoxic activity was evaluated in THP-1 human leukemia cells using MTT assay, flow cytometry, and biochemical analyses. Antimicrobial activity was assessed against Streptococcus pyogenes via agar diffusion. Gene expression of BCL2, PI3K, and CDK8 was measured to elucidate mechanisms of action.

Among all tested extracts, PPE-EA showed the strongest dual activity, reducing THP-1 cell viability by over 50% at 100 µg/mL and inhibiting S.
pyogenes with a 10.5 ± 1.1 mm zone. Nano-encapsulation enhanced both effects, reducing the IC₅₀ from 1.48 ± 0.03 µg/mL to 0.19 ± 0.01 µg/mL and increasing the bacterial inhibition zone to 15.6 ± 0.5 mm. n-PPE-EA induced apoptosis, cell cycle arrest, elevated catalase activity, and reduced malondialdehyde levels. It also downregulated BCL2, PI3K, and CDK8 expression.

The nano-formulated PPE-EA demonstrated potent cytotoxic and antimicrobial activities, with enhanced efficacy attributed to improved bioavailability and modulation of apoptotic and cell cycle pathways. These findings support its potential as a multifunctional therapeutic agent in integrative cancer care.

The online version contains supplementary material available at 10.1186/s12906-026-05291-9.