Arecoline

About: Arecoline is a research topic. Over the lifetime, 744 publications have been published within this topic receiving 16015 citations. The topic is also known as: methylarecaiden & methylarecaidin.

Synthesis and muscarinic activity of a series of tertiary and quaternary N-substituted guvacine esters structurally related to arecoline and arecaidine propargyl ester.

Abstract: A series of tertiary and quaternary N-substituted guvacine (1,2,5,6-tetrahydro-3-carboxy-pyridine) methyl and propargyl esters have been synthesized and tested for muscarinic/antimuscarinic activity on rat ileum and electrically paced left atria. Arecoline and arecaidine propargyl ester (APE) as well as their corresponding N-demethyl derivatives, guvacoline (norarecoline) and guvacine propargyl ester, acted as full agonists at both atrial and ileal muscarinic receptors (range of pD2-values 6.09-8.07). However, in both preparations arecoline and APE were clearly more potent (up to 15-fold) than their N-demethyl analogues. Replacement of the N-methyl group in arecoline and APE by larger substituents (ethyl, n-propyl, n-butyl, benzyl, phenylethyl) as well as N-methylation resulted in a decrease or even a complete loss of agonistic activity. In both organs, the propargyl esters usually showed higher potency than the corresponding methyl ester analogues. N-Ethylguvacine propargyl ester and APE methiodide displayed pronounced agonistic activity in the atria (pD2 approximately 6.5; intrinsic activity = 0.79 and 0.67, respectively) but behaved as competitive antagonists in the ileum (pA2 = 6.06 and 5.62, respectively). Beside the lower sensitivity to muscarinic agonists of the rat ileum as compared to rat atria, the cardioselective stimulant action of both agents may also be due to their ability to recognize structural differences between atrial M2 alpha and ileal M2 beta muscarinic receptor subtypes.

Areca nut extracts reduce the intracellular reactive oxygen species and release of myeloperoxidase by human polymorphonuclear leukocytes.

Abstract: Background and Objective: Polymorphonuclear leukocytes (PMN) represent the first line of host defense. Areca nut extract inhibits the bactericidal activity of, and the release of superoxide anion (O2– ) by, PMN. This study investigated the effects of areca nut extract on the intracellular production of reactive oxygen species (ROS) and on the extracellular release of lysosomal enzyme, myeloperoxidase (MPO), by PMN. The effects of arecoline, a principal component of areca nut, were also examined. Material and Methods: Human PMN were treated with various concentrations of areca nut extract or arecoline followed by treatment with Hanks' balanced salt solution, with or without cytochalasin B and fMet-Leu-Phe (CB/fMLP). The viability of PMN was determined using propidium iodide staining and flow cytometry. The presence of intracellular ROS was determined using 2′,7′-dichlorofluorescin diacetate and fluorometry. MPO release was determined using a substrate assay. Results: Areca nut extract (25 and 50 µg/ml) significantly decreased the viability of PMN. The intracellular levels of ROS and the extracellular release of MPO were induced in PMN by CB/fMLP. Exposure of PMN to areca nut extract (up to 25 µg/ml) or to arecoline (up to 2 mg/ml) did not directly affect the levels of ROS and MPO activity. However, under conditions that did not affect the viability of PMN, the ability of CB/fMLP to trigger production of intracellular ROS and release of MPO in human PMN was significantly suppressed by areca nut extract and arecoline. Conclusion: Areca nut impaired the activation of PMN by CB/fMLP that might decrease the effectiveness of PMN in the host defense. Alternatively, exposure of PMN to areca nut extract could decrease the capacity of PMN to damage tissues.

Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts.

Abstract: Aim The aim of the present study was to investigate the in vitro antifibrogenic effects of Centella asiatica Linn (CA) and its bioactive triterpene aglycone asiatic acid (AA) on arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). Methods An ethanolic extract of CA was prepared, and AA was purchased commercially. High-performance thin-layer chromatography (HPTLC) was performed to quantify AA in the CA extract; colorimetric assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was performed to determine an half-maximal inhibitory concentration. HBF were cultured and stimulated with arecoline. The inhibitory effects of CA and AA at different concentrations were assessed using gene-expression studies on fibrosis-related markers: transforming growth factor-β1, collagen 1 type 2, and collagen 3 type 1. The stimulatory effect of arecoline and the inhibitory effect of AA on fibroblast morphology and extracellular matrix were assessed qualitatively using Masson trichrome stain. Results The HPTLC analysis determined 1.2% AA per 100 g of CA extract. Arecoline produced a concentration-dependent increase in the fibrotic markers, treatment with CA significantly downregulated fibrotic markers at higher concentrations, and AA downregulated at lower concentrations. Arecoline altered fibroblast morphology and stained strongly positive for collagen, and AA treatment regained fibroblast morphology with faint collagen staining. Conclusion CA and AA can be used as antifibrotic agents.

Alkaloids from Areca (Betel) Nuts and Their Effects on Human Sperm Motility In Vitro

Abstract: An improved high-performance liquid chromatography (HPLC) method was established to rapidly and simultaneously determine 3 main alkaloids (arecoline, arecaidine, and guvacine) in areca (betel) nuts (AN), and 12 AN samples from the main betel palm growing areas on the Chinese Mainland were collected and determined. Semen samples from acceptable volunteers were treated in vitro with different concentrations of the 3 alkaloids to evaluate the effects on sperm motility (SM). Highly motile spermatozoa were selected from the samples and divided into 5 equal fractions. Various concentrations of each alkaloid were added to 4 of the 5 fractions, and 1 fraction was used as a control. All fractions were incubated for 4 h. A computer-aided sperm analysis system was used to measure 5 SM parameters, motility, average path velocity, straight-line velocity, curvilinear velocity, linearity, and amplitude of lateral head displacement. The results showed that the contents of the amount of alkaloids in AN differed markedly in different places in China and were higher in the kernel than in the husk, and higher in dried AN than in fresh AN. Arecoline had the strongest reduction effect on human SM and the effect was strongly dose dependent. Arecaidine had a much weaker reduction effect than arecoline, and guvacine had the least reduction effect. These findings also demonstrate that betel quid could have adverse effects on the gonadal functions of betel quid consumers.

Lead-induced changes in muscarinic cholinergic sensitivity.

Abstract: This study was undertaken to determine whether the biochemical changes in cholinergic systems produced by lead exposure result in corresponding changes in cholinergic sensitivity in vivo. Rats chronically exposed from weaning to 0, 50 or 150 ppm lead (Pb) acetate in drinking water were trained to discriminate the stimulus properties of a dose of 1.75 mg/kg of the muscarinic cholinergic agonist, arecoline, from saline, using standard operant food reinforced drug discrimination procedures. Following acquisition of the discrimination, various doses of arecoline, another muscarinic agonist, oxotremorine, a nicotinic agonist, nicotine, and the GABAA modulator, pentobarbital, were substituted for the arecoline training dose, and the ability of various doses of the muscarinic antagonist, atropine, to antagonize the discriminative stimulus properties of the 1.75 mg/kg dose of arecoline were examined. Arecoline and oxotremorine produced dose-related increases in drug lever responding, while pentobarbital produced a partial generalization that was not dose-related. Arecoline's stimulus properties were substantially antagonized by atropine. Pb exposure significantly increased sensitivity to oxotremorine but not to arecoline, and attenuated the ability of some doses of atropine to antagonize the stimulus properties of arecoline. These findings demonstrate altered cholinergic sensitivity in response to environmentally relevant levels of lead in blood, and raise the possibility of cholinergic system disturbances in the behavioral manifestations produced by lead exposure.