Atherogenic effect of Arecoline: A computational study

Abstract

There are over 600 million people worldwide covering Asian and Oceanic countries including India have the habit of chewing areca nut as masticator in different forms. Arecoline (C8H13NO2) has been reported as one of the abundant constituents of areca nut. A good number of scientific publications have made Arecoline responsible for oral cancer. Based on observation from clinical situation in North East India, one of the most betel quid chewing region of the country, we suspected a link between consumption of areca nut and Cerebro Vascular Disease like stroke. Therefore, we considered Low Density Lipoprotein (LDL) receptor as target and Arecoline as ligand and studied ligand –target interaction using computational tools. Also we considered High Density Lipoprotein (HDL) receptor as another target to see if Arecoline has any binding potential with it over and above LDL receptor. Docking result indicated that Arecoline and Cholesterol both, have affinity towards extracellular domain of Human LDL receptor but affinity of Arecoline is much higher (-12.3560.) than that of Cholesterol(-0.1810). Docking of Arecoline and 1, 2-Hexyl-1- cyclopentanone thiosemicarbazone (thiosemicarbazone) with Bovine HDL receptor showed that Arecoline also has the potential (Score, -6.2690Kcal/Mol) to block HDL receptor though its potential is less than that (score, -10.0509 Kcal/Mol) of control (thiosemicarbazone). We, therefore, suggest that by inhibiting endocytosis of LDL cholesterol because of blocking LDL receptor function and also by preventing LDL cholesterol uptake by liver from blood because of interference with HDL receptor, Arecoline may contribute to atherosclerosis. The study therefore, indicates a positive correlation between chewing of betel quid and Cerebro Vascular Disease.

Association of betel nut chewing with exercise performance in a military male cohort: the CHIEF study

“…With regard to the cardiovascular system, current betel nut chewing would increase HR, irrespective of the frequency of usage, due to central sympathetic response, but the effect on BP may vary by the peripheral cholinergic effect, resulting in a fall of the diastolic component 4. Coronary spasm by parasympathomimetic effect of arecoline in betel nut23 has been reported to influence exercise performances. In addition, arecoline consumptions could increase bronchoconstriction in a dose-dependent manner and decrease the forced expiratory volume in 1 s by 30% 24 25…”

A review of the systemic adverse effects of areca nut or betel nut

“…[ 15 16 17 ] Arecoline has a blocking effect on the high-density lipoprotein receptor and inhibits the uptake of low-density lipoprotein by the liver thus leading to enhanced atherogenesis and its parasympathomimetic effect leading to spasm of the coronary arteries, both of which predispose to coronary artery diseases. [ 18 19 ] Researchers in Taiwan have shown a relative risk of coronary artery disease in areca nut chewers to be 3.5 in men and 1.37 in women, and the risk increases with the amount consumed. [ 20 21 ] Studies have also linked areca nut chewing to cardiac arrhythmias like paroxysmal supraventricular tachycardia (PSVT), even causing death in a case despite exhaustive treatment.…”

Oral submucous fibrosis: an update

“…This might be linked to an increased risk for metabolic diseases, hypertension, and cardiovascular disease. 83 , 84 A possible link between betel quid chewing and cardiovascular disease could be arecoline. Arecoline is capable of blocking the high-density lipoprotein receptor with a higher affinity than cholesterol.…”