Acaciasaligna extract alleviates quetiapine-induced sexual toxicity in male albino rats: Insights from UPLC-MS/MS metabolite profiling, structural and PI3K/NF-κB pathway assessments
Shimaa Mohammad Yousof,
Shaimaa A. Shehata,
Ezzat A. Ismail,
Samar M. Abd El-moneam,
Basma S.A. Mansour,
Mohamed A. Farag,
Abdelsamed I. Elshamy,
Abd El-Nasser G. El Gendy,
Ahmed Serag,
Noha M. Abd El-Fadeal,
Rehab Ibrahim Abdel-Karim,
Mostafa M. Mostafa,
Dina H. El-Sheikh,
Mohamed A. Zayed
Affiliations
Shimaa Mohammad Yousof
Medical Physiology Department, Faculty of Medicine, King Abdulaziz University, Rabigh Branch, 21589, Saudi Arabia; Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt; Neuroscience and Geroscience Unit, King Fahad Research Centre, King Abdulaziz University, KSA; Corresponding author. Medical Physiology Department, Faculty of Medicine, King Abdulaziz University, Rabigh Branch, 21589, Saudi Arabia.
Shaimaa A. Shehata
Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine- Suez Canal University, Ismailia, 41522, Egypt
Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt
Basma S.A. Mansour
Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt
Mohamed A. Farag
Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini, Giza 12613, Egypt
Abdelsamed I. Elshamy
Department of Natural Compounds Chemistry, National Research Center, Dokki, Giza 12622, Egypt; Corresponding author. Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt.
Abd El-Nasser G. El Gendy
Medicinal and Aromatic Plants Research Department, National Research Centre, 33 El Bohouth St., Dokki, Giza, 12622, Egypt
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt; Biochemistry Department, Ibn Sina National College for Medical Studies, Jeddah, 22421, Saudi Arabia
Rehab Ibrahim Abdel-Karim
Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine- Suez Canal University, Ismailia, 41522, Egypt
Mostafa M. Mostafa
Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Rabigh Branch, 21589, Saudi Arabia; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Kasr Al Ainy, Cairo, 11562, Egypt
Dina H. El-Sheikh
Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini, Giza 12613, Egypt; Medical Physiology Department, Faculty of Medicine, Prince Sattam Bin Abdulaziz University, Al Kharj Branch, 16273, Saudi Arabia; Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
Mohamed A. Zayed
Medical Physiology Department, Faculty of Medicine, King Abdulaziz University, Rabigh Branch, 21589, Saudi Arabia; Medical Physiology Department, Faculty of Medicine, Menoufia University, Menoufia, 13829, Egypt; Neuroscience and Geroscience Unit, King Fahad Research Centre, King Abdulaziz University, KSA
Background: Quetiapine (QET) abuse has increased due to its anxiolytic and hedonic effects, necessitating protective adjunct treatments. Acacia saligna (A. saligna) flowers, used in traditional medicine, have potential health benefits. Aim: To investigate the protective role of A. saligna flower extract against QET-induced sexual toxicity, and to elucidate the possible underlying mechanisms through metabolomic and physiological studies. Methods: A. saligna extract was subjected to metabolite profiling via High-Resolution Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI–qTOF-MS). Forty-eight adult male albino rats were assigned into six groups for 30 days. The intracavernosal pressure (ICP), semen, biochemical, hormonal, histological, genetic and Western blot (WB) analyses were determined. Results: A. saligna extract is rich in phenolic compounds, flavonoids, tannins, and unsaturated fatty acids. QET significantly decreased ICP and negatively affected semen parameters. A. saligna mitigated decreased sperm motility and ameliorated overexpressed proinflammatory genes in QET-55 group. A. saligna ameliorated the reduction of the antioxidant biomarkers, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), concurrent with downregulation of the nuclear factor kappa B (NF-κB) protein. A. saligna counteracted the disrupted testicular and prostatic structures revealed by histological examination. Conclusion: The extract from A. saligna, which contains a high concentration of antioxidants and anti-inflammatory chemicals, effectively mitigates sexual toxicity caused by QET. This study provided the first known explanation of the hypothesized processes behind the protective properties of A. saligna through biological, biochemical, and histological parameters. The results emphasize the potential of A. saligna as a safeguarding agent against drug-induced sexual toxicity.
