Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers

Pharmaceuticals

Yasmine H. Ahmed¹  El-Shaymaa Abdel-Sattar²  Hamad S. Alyami³  Dalia I. Hamdan⁴  Mohamed A. A. Orabi⁵  Mohamed E. Abouelela⁶  Katsuyoshi Matsunami⁷  Reham A. Naggar⁸  Heba M. A. Khalil⁹  Dalia Zaafar^1,10 

[1] Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt;Department of Medical Microbiology and Immunology, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt;Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia;Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Menoufia University, Shibin Elkom 32511, Egypt;Department of Pharmacognosy, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia;Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut-Branch, Assiut 71524, Egypt;Department of Pharmacognosy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8553, Japan;Department of Pharmacology and Toxicology, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology (MUST), 6th October, Giza 12566, Egypt;Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt;Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Information and Technology, Cairo 11311, Egypt;

关键词: Carissa macrocarpa;    cytotoxicity;    UPLC-ESI-MS/MS;    doxorubicin;    neurotoxicity;    molecular docking;   

DOI  :  10.3390/ph14121305

来源: DOAJ

【 摘 要 】

Chemotherapeutic-related toxicity exacerbates the increasing death rate among cancer patients, necessitating greater efforts to find a speedy solution. An in vivo assessment of the protective effect of the C. macrocarpa leaves polar fraction of hydromethanolic extract against doxorubicin (Dox)-induced neurotoxicity was performed. Intriguingly, this fraction ameliorated Dox-induced cognitive dysfunction; reduced serum ROS and brain TNF-α levels, upregulated the brain nerve growth factor (NGF) levels, markedly reduced caspase-3 immunoexpression, and restored the histological architecture of the brain hippocampus. The in vivo study results were corroborated with a UPLC-ESI-MS/MS profiling that revealed the presence of a high percentage of the plant polyphenolics. Molecular modeling of several identified molecules in this fraction demonstrated a strong binding affinity of flavan-3-ol derivatives with TACE enzymes, in agreement with the experimental in vivo neuroprotective activity. In conclusion, the C. macrocarpa leaves polar fraction possesses neuroprotective activity that could have a promising role in ameliorating chemotherapeutic-induced side effects.

【 授权许可】

Unknown