Journal
PHARMACEUTICALS
Volume 14, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ph14121305
Keywords
Carissa macrocarpa; cytotoxicity; UPLC-ESI-MS; MS; doxorubicin; neurotoxicity; molecular docking
Categories
Funding
- ministry of education and the deanship of research, Najran University, Kingdom of Saudi Arabia [NU/MRC/10/332]
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The polar fraction of C. macrocarpa leaves was found to possess neuroprotective activity against doxorubicin-induced toxicity, improving cognitive function, reducing oxidative stress and inflammation, increasing NGF levels, reducing apoptosis, and restoring brain histological architecture. Molecular modeling showed that flavan-3-ol derivatives in the fraction have a strong binding affinity with TACE enzymes, supporting the observed neuroprotective effects in vivo. This suggests a promising role for this fraction in alleviating chemotherapy-induced side effects.
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-alpha 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.
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