There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

The WHO reports that billions of people and animals in tropical and subtropical regions are affected by helminthiasis as neglected tropical disease. It is predominant in underdeveloped areas; nevertheless, the increase in the number of travelers and migrants has made this infection more common. The current mass drug treatment produces severe side effects and many strains of helminths are resistant to them. None of the chemotherapeutic drugs meets the ideal requirements of anthelmintics, such as broad spectrum of activity, single dose cure, free from side effect and cost-effectiveness. Today, many researchers are screening the traditional herbal system in search of the anthelmintic herbal constituents which overcome all the problems of synthetic drugs. Several researchers proclaim anthelmintic activity of herbal medicines by using different experimental models. The present review demonstrates natural product drug discovery, outlining potential of herbal constituents from natural sources as natural leads against helminthiasis.