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Biomolecules
Volume 15
Issue 11
10.3390/biom15111605
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Article

Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms

by
M. Alfawaz
1,
Ekramy M. Elmorsy
2,3,
Ahmad Najem Alshammari
1,
Marwa Nagy Emam
4,5,
Islam Ibrahim Hegab
4,5,
Aly A. M. Shaalan
6,7,
Manal S. Fawzy
2,* and
Lina Abdelhady Mohammed
8
1
Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia
2
Center for Health Research, Northern Border University, Arar 73213, Saudi Arabia
3
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
4
Physiology Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
5
Department of Biophysiology, Ibn Sina National College for Medical Studies, Jeddah 22413, Saudi Arabia
6
Department of Anatomy, Faculty of Medicine, Jazan University, Jazan 45142, Saudi Arabia
7
Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
8
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt
*
Author to whom correspondence should be addressed.
Biomolecules 2025, 15(11), 1605; https://doi.org/10.3390/biom15111605
Submission received: 29 October 2025 / Revised: 7 November 2025 / Accepted: 12 November 2025 / Published: 15 November 2025
(This article belongs to the Special Issue The Role of Nanoparticles in Tumor Treatment)
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Abstract

This study, for the first time, evaluated the therapeutic potential of resveratrol-loaded phytosome nanoparticles (RES-PNPs) against Ehrlich ascites carcinoma (EAC) and associated testicular dysfunction, compared with free resveratrol (RES). Ninety male Swiss albino mice were divided into six groups, (1) control; (2) RES (10 mg/kg/day, orally); (3) RES-PNPs (10 mg/kg/day, orally); (4) EAC, induced by intraperitoneal injection of 2.5 × 106 cells; (5) EAC + RES; and (6) EAC + RES-PNPs, treated for 20 days post-tumor inoculation. Tumor growth parameters, reproductive function, antioxidant enzyme activities, inflammatory mediators, apoptotic markers, and histopathological features were assessed. Additionally, in silico docking was performed to identify molecular targets mediating RES effects. RES-PNPs markedly reduced tumor volume, ascitic cell viability, and body weight gain while significantly prolonging survival compared with free RES. Molecular assays revealed enhanced pro-apoptotic signaling (increased Bax and Caspase-3, decreased Bcl-2), suppression of vascular endothelial growth factor (VEGF), and inhibition of COX-2 with reduced TNF-α, IFN-γ, and IL-1β levels. RES-PNPs also restored semen quality, normalized reproductive hormones, elevated antioxidant enzyme activities, and reduced lipid and protein oxidation, corroborated by notable testicular histological protection. In conclusion, Resveratrol-loaded phytosome nanoparticles provide superior anti-tumor, antioxidant, anti-inflammatory, and pro-apoptotic benefits compared with free RES. These findings highlight RES-PNPs as a potent and stable nanoformulation for effective EAC suppression and preservation of male reproductive integrity.
Keywords: resveratrol-loaded nanoparticles; Ehrlich ascites carcinoma; testicular function; anti-angiogenic; antioxidant; anti-inflammatory; apoptosis resveratrol-loaded nanoparticles; Ehrlich ascites carcinoma; testicular function; anti-angiogenic; antioxidant; anti-inflammatory; apoptosis

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MDPI and ACS Style

Alfawaz, M.; Elmorsy, E.M.; Alshammari, A.N.; Emam, M.N.; Hegab, I.I.; Shaalan, A.A.M.; Fawzy, M.S.; Mohammed, L.A. Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms. Biomolecules 2025, 15, 1605. https://doi.org/10.3390/biom15111605

AMA Style

Alfawaz M, Elmorsy EM, Alshammari AN, Emam MN, Hegab II, Shaalan AAM, Fawzy MS, Mohammed LA. Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms. Biomolecules. 2025; 15(11):1605. https://doi.org/10.3390/biom15111605

Chicago/Turabian Style

Alfawaz, M., Ekramy M. Elmorsy, Ahmad Najem Alshammari, Marwa Nagy Emam, Islam Ibrahim Hegab, Aly A. M. Shaalan, Manal S. Fawzy, and Lina Abdelhady Mohammed. 2025. "Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms" Biomolecules 15, no. 11: 1605. https://doi.org/10.3390/biom15111605

APA Style

Alfawaz, M., Elmorsy, E. M., Alshammari, A. N., Emam, M. N., Hegab, I. I., Shaalan, A. A. M., Fawzy, M. S., & Mohammed, L. A. (2025). Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms. Biomolecules, 15(11), 1605. https://doi.org/10.3390/biom15111605

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