Natural Product-Based Nanomedicine in the Alleviation of Neurocognitive Impairment Induced by Chemotherapy

Summary

Chemotherapy-induced cognitive impairment has recently recognized as a real and highly common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors, a condition that is known by Chemobrain. Oxaliplatin is a widely used chemotherapeutic agent for colorectal cancers that exerts its anticancer effects mainly via DNA damage. It was found to bind preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and transcription. Thus, it may cause neurological and hematological side effects (leukopenia and neutropenia, thrombocytopenia, and anemia). Besides, several case reports suggested that cancer patients on oxaliplatin chemotherapy suffer from cognitive impairment and hepatotoxicity, during and after oxaliplatin course. Plant kingdom provides an everlasting source of naturally occurring drugs and phytoconstituents. Thus, in this project we aimed to examine the efficacy of natural products belonging to Family Lamiaceae that have long been known by their neuroprotective effect.  Drugs derived from natural origin such as Basil, Salvia, Origanum as well as Rosemary, their bioactive fractions and essential oils will be examined in vitro for their neuroprotective and anti-inflammatory effects. This/these bioactive fraction(s) will be formulated as nanoparticles and will be examined in vivo for its/their effectiveness in the alleviation of neurological dysfunction and hepatotoxicity induced by oxaliplatin.  This will be assessed in vivo both in the hippocampi and prefrontal cortices of rats via evaluating the behavioral alterations (passive avoidance and locomotor activity), oxidative stress markers (Catalase, Reduced glutathione and MDA levels) in addition to determining the inflammatory response markers (GFAP, TNF-alpha, NF-kB and IL-1beta). Phytochemical profiling of the bioactive drugs will be done using Liquid Chromatography coupled with Mass Spectroscopy (LC-MS) and/ or Gas Chromatography coupled with Mass Spectrometry (GC-MS) techniques to identify the major compounds. The identified compounds will be subjected to molecular modelling in an effort to interpret the probable mode of action. Whenever possible we can isolate these major compounds and/or purchase standards of the major constituents to be examined in vitro or in vivo. Thus, our optimum goal is to find out naturally derived drugs formulated in a suitable dosage form to alleviate chemobrain easier to be accepted by several categories of patients in the society than synthetic drugs with optimum bioavailability to be utilized by pharmaceutical industries.

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