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Article

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

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Department of Pharmacognosy, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia
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Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
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Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut-Branch, Assiut 71524, Egypt
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Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Information and Technology, Cairo 11311, Egypt
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Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
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Department of Pharmacology and Toxicology, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology (MUST), 6th October, Giza 12566, Egypt
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Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia
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Department of Medical Microbiology and Immunology, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt
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Department of Pharmacognosy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8553, Japan
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Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Menoufia University, Shibin Elkom 32511, Egypt
*
Authors to whom correspondence should be addressed.
Academic Editor: Woo-Yang Kim
Pharmaceuticals 2021, 14(12), 1305; https://doi.org/10.3390/ph14121305
Received: 15 November 2021 / Revised: 4 December 2021 / Accepted: 10 December 2021 / Published: 14 December 2021
(This article belongs to the Section Pharmacology)
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. View Full-Text
Keywords: Carissa macrocarpa; cytotoxicity; UPLC-ESI-MS/MS; doxorubicin; neurotoxicity; molecular docking Carissa macrocarpa; cytotoxicity; UPLC-ESI-MS/MS; doxorubicin; neurotoxicity; molecular docking
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MDPI and ACS Style

Orabi, M.A.A.; Khalil, H.M.A.; Abouelela, M.E.; Zaafar, D.; Ahmed, Y.H.; Naggar, R.A.; Alyami, H.S.; Abdel-Sattar, E.-S.; Matsunami, K.; Hamdan, D.I. Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers. Pharmaceuticals 2021, 14, 1305. https://doi.org/10.3390/ph14121305

AMA Style

Orabi MAA, Khalil HMA, Abouelela ME, Zaafar D, Ahmed YH, Naggar RA, Alyami HS, Abdel-Sattar E-S, Matsunami K, Hamdan DI. Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers. Pharmaceuticals. 2021; 14(12):1305. https://doi.org/10.3390/ph14121305

Chicago/Turabian Style

Orabi, Mohamed A. A., Heba M. A. Khalil, Mohamed E. Abouelela, Dalia Zaafar, Yasmine H. Ahmed, Reham A. Naggar, Hamad S. Alyami, El-Shaymaa Abdel-Sattar, Katsuyoshi Matsunami, and Dalia I. Hamdan. 2021. "Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers" Pharmaceuticals 14, no. 12: 1305. https://doi.org/10.3390/ph14121305

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