Pomegranate Peel Extract-loaded Chitosan Nanoparticles Exhibit Anticancer and Hepatorenal Activities Against Solid Ehrlich Carcinoma

Abstract

INTRODUCTION: Conventional cancer treatments have several limitations, including toxicity and reduced selectivity, which have prompted the exploration of novel therapeutic strategies. Pomegranate peel extract (PPE) demonstrates significant anticancer, antioxidative, and antiinflammatory properties. This study was conducted with the purpose of improving the anticancer specificity of PPE using chitosan nanoparticles as drug delivery against subcutaneous Ehrlich Carcinoma (SEC) in a mouse model. METHODS: Mice were inoculated subcutaneously in the dorsal flank with Ehrlich ascites carcinoma (EAC) cells, at a concentration of 2.5 × 10⁶ cells per mouse on the 0th day. The experiment involved five groups: control, SEC, SEC+ PPE (200 mg/kg, orally), SEC+ chitosan NPs (60 mg/kg, orally), and SEC+ PPE nanoparticles (PPENPs) (60 mg/kg, orally). Each group received the corresponding treatment for 3 weeks. RESULTS: Oral administration of PPENPs exerted a significant antitumor effect via reducing tumor size and arginase activity within the tumor microenvironment while enhancing oxidative stress and inducing collagen accumulation in tumor tissue. Moreover, the PPENPs-treated group showed a significant increase in caspase-3 expression and a decrease in TNF-α levels, indicating activated apoptosis and reduced inflammation. On the other hand, PPENPs preserved hepatorenal function markers near normal levels and attenuated oxidative stress in liver and kidney tissues. DISCUSSION: PPENPs effectively suppressed tumor proliferation by inducing ROS-mediated apoptotic cell death, increasing apoptotic markers, and modulating inflammatory responses. Additionally, PPENPs reduced systemic oxidative stress and protected vital organs from tumor-induced damage, demonstrating a systemic protective profile alongside their anticancer effects. CONCLUSION: Thus, PPENPs exhibit dual roles as promising anticancer and hepatorenal protective agents against subcutaneous Ehrlich carcinoma.