Screening of plant extracts in achieving novel strategy in promoting efficacy and combat Cisplatin-induced neurotoxicity

Abstract ID 93616 Poster Board 012 Chemotherapy is an elementary cancer treatment employed to target rapidly dividing cancer cells. Among various therapeutic approaches such as immunotherapy, chemotherapy, targeted therapy, radiation, and surgery, chemotherapy is frequently considered the most successful. However, its efficacy encounters obstacles due to drug resistance, challenges in treatment selectivity, and the occurrence of severe adverse effects, particularly neurotoxicity. Cisplatin, a platinum-based chemotherapy agent, faces significant adverse effects and resistance mechanisms when used as a standalone treatment, ultimately resulting in therapeutic shortcomings. In response to these challenges, combination therapies incorporating natural products are emerging as a promising and innovative strategy. Our research aims to identify natural products with the potential to mitigate the unwanted consequences associated with chemotherapy treatment. This investigation screened multiple plant extracts from our laboratory9s archive in preliminary assays using a mouse-hippocampal-neuron (HT-22 cell line). The objective was to evaluate the combined effect of cisplatin treatment and our plant extracts. This assessment aims to gauge the efficacy of the plant extracts in preventing chemotherapy-induced neurotoxicity. In the initial evaluation encompassing 12 plant extracts, the Areca catechu (AC-ea) extract demonstrated notable efficacy in preliminary MTT assays, exhibiting a capacity to protect HT-22 cells during simultaneous administration with cisplatin at the IC₇₅ dose. Subsequent assays involving the determination of reactive oxygen species (ROS) and the quantification of apoptosis-related proteins (Caspase-3 and p53) indicated significant protection in experimental groups subjected to cisplatin and AC-ea treatment. Further LCMS analysis aimed at identifying potential phyto-compounds revealed the presence of several compounds, including Arecoline, Salicylic acid, Catechin, and Myxoxanthin. These compounds have been previously documented for their neuroprotective properties and anti-neuroinflammatory attributes. The findings collectively suggest the potential of AC-ea, rich in these compounds, as a promising candidate for further exploration in the context of neuroprotection and mitigating cisplatin-induced neurotoxicity. Our ongoing experiments seek to further validate the observed protective effects and to delineate the molecular mechanisms that underlie these protective attributes. By this evaluation, our goal is to contribute to the evolution of cancer treatment by influencing the efficacy and enhancing the tolerability of the chemotherapeutic treatment paradigm. The Second Century Fund Chulalongkorn University (C2F).