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.

Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline.

Abstract: // Tung Yuan Wang 1, * , Chih-Yu Peng 1, 2, * , Shiuan-Shinn Lee 4 , Ming-Yung Chou 1, 2, 3 , Cheng-Chia Yu 1, 2, 3 , Yu-Chao Chang 1, 2 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 School of Public Health, Chung Shan Medical University, Taichung, Taiwan * These authors contributed equally to this work Correspondence to: Cheng-Chia Yu, email: ccyu@csmu.edu.tw Yu-Chao Chang, email: cyc@csmu.edu.tw Keywords: arecoline, cancer stemness, oral squamous cell carcinomas Received: November 09, 2015 Accepted: August 13, 2016 Published: August 20, 2016 ABSTRACT Oral squamous cell carcinoma (OSCC), one of the most deadliest malignancies in the world, is caused primarily by areca nut chewing in Southeast Asia. The mechanisms by which areca nut participates in OSCC tumorigenesis are not well understood. In this study, we investigated the effects of low dose long-term arecoline (10 μg/mL, 90-days), a major areca nut alkaloid, on enhancement cancer stemness of human oral epithelial (OE) cells. OE cells with chronic arecoline exposure resulted in increased ALDH1 population, CD44 positivity, stemness-related transcription factors (Oct4, Nanog, and Sox2), epithelial-mesenchymal transdifferentiation (EMT) traits, chemoresistance, migration/invasiveness/anchorage independent growth and in vivo tumor growth as compared to their untreated controls. Mechanistically, ectopic miR-145 over-expression in chronic arecoline-exposed OE (AOE) cells inhibited the cancer stemness and xenografic. In AOE cells, luciferase reporter assays further revealed that miR-145 directly targets the 3′ UTR regions of Oct4 and Sox2 and overexpression of Sox2/Oct4 effectively reversed miR-145-regulated cancer stemness-associated phenomenas. Additionally, clinical results further revealed that Sox2 and Oct4 expression was inversely correlated with miR-145 in the tissues of areca quid chewing-associated OSCC patients. This study hence attempts to provide novel insight into areca nut-induced oral carcinogenesis and new intervention for the treatment of OSCC patients, especially in areca nut users.

Effects of long-term continuous infusion of the muscarinic cholinergic agonist arecoline on verbal memory in dementia of the Alzheimer type.

Abstract: Alzheimer's disease (AD) is accompanied by depletion of cholinergic markers in the central nervous system. In an attempt to improve cognitive function in AD, arecoline (a muscarinic cholinergic receptor agonist) was given to patients with probable or possible AD in a two-phase design, and verbal memory function was examined. First, escalating doses of arecoline, range .5-40 mg/day, were administered by continuous intravenous infusion over a 2-week period. Based on neuropsychological test performance, an optimal dose of arecoline was identified, and this dose then was infused continuously for 5 days in a double-blind, placebo-controlled, counter-balanced trial. Long-term recall on a selective reminding task was significantly improved (from 11.8 to 20.1 words, p less than .05) during dose finding by arecoline at 4 mg/day. Two of eight patients were nonresponders; that is, they showed no improvement at any dose during the dose-finding study. Responders demonstrated significant improvement on total recall (p less than .05) during the double-blind study. These results indicate that some patients demonstrate reliable improvements of verbal memory during arecoline treatment.

Pharmacological investigation of Areca catechu extracts for evaluation of learning, memory and behavior in rats

Abstract: Areca catechu Linn is one of the stimulant masticatory crude materials of Indian system of medicine. The present study was done to evaluate the effect of Areca catechu Linn extract on learning and memory in rats using radial arm maze. The extract used for study was of two different types of Areca catechu namely, wet and dried Areca catechu . Three groups of rats each consisting of seven animals were used for the purpose. Test groups were given 500mg/kg p.o of wet Areca catechu extract and dried Areca catechu extract respectively. It was observed that wet Areca catechu extract showed greater increase in spatial memory and learning in comparison to the control group of rats. Hence increase in spatial memory could be because of higher amount of arecoline present in wet Areca catechu extract. DOI: http://dx.doi.org/10.3329/icpj.v1i6.10533 International Current Pharmaceutical Journal 2012, 1(6): 128-132

Regulation of interleukin-6 expression by arecoline in human buccal mucosal fibroblasts is related to intracellular glutathione levels.

Abstract: Objectives: Cytokines play an important role in regulating fibroblast function and is likely to play a key role in regulating the initiation and progression of scarring in any fibrotic disease Interleukin-6 (IL-6) has been implicated in the development of a variety of fibrotic diseases The aim of this study was to compare IL-6 expression in fibroblasts cultured from normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induce IL-6 expression Methods: mRNA level of IL-6 in fibroblasts from OSF was compared with normal buccal mucosa The effects of arecoline, the major areca nut alkaloid, on IL-6 expression in normal human buccal mucosa fibroblasts (BMFs) were measured in vitro mRNA was quantified with AlphaImager 2000 To determine whether glutathione (GSH) levels were important in the induction of IL-6 by arecoline, we pretreated cells with 2-oxothiazolidine-4-carboxylic acid (OTZ) to boost GSH levels or with buthionine sulfoximine (BSO) to deplete GSH Results: Fibroblasts derived from OSF exhibited higher IL-6 gene expression than BMF in mRNA levels (P < 005) The exposure of quiescent BMF to arecoline resulted in the elevation of IL-6 mRNA expression in a dose-dependent manner (P < 005) IL-6 gene regulated by arecoline correlated with intracellular GSH levels in BMF Arecoline at a concentration of 129 μM induced about 27-fold IL-6 mRNA levels over the 6-h incubation period However, BSO enhanced the IL-6 mRNA levels by 39-fold (P < 005) In addition, OTZ was found to marginally reduce the arecoline-induced IL-6 expression by about 17-fold (P < 005) Conclusions: Taken together, these results suggest that IL-6 expression is significantly upregulated in OSF fibroblasts in areca quid chewers and arecoline may be responsible for the enhanced IL-6 expression In addition, the regulation of IL-6 expression induced by arecoline is critically dependent on the intracellular GSH concentrations

Investigations on the CNS sites of action of the discriminative stimulus effects of arecoline and nicotine.

Abstract: The role of the dorsal hippocampus (DH) and mesencephalic reticular formation (MRF) in mediating the discriminative stimulus (DS) effects of nicotine and arecoline was assessed. In rats trained to discriminate nicotine (1.14 mg/kg) from saline, peripherally administered nicotine generalized to injection of nicotine, but not arecoline, directly into the DH and MRF. The stimulus effect of centrally administered nicotine was antagonized by peripherally administered mecamylamine, but not atropine. Response rate decreases were also observed after nicotine injection into either central site. In rats trained to discriminate arecoline (1.74 mg/kg) from saline, peripherally administered arecoline did not generalize to the direct injection of arecoline into the DH and MRF. However, a decrease in response rates was observed after arecoline injection into either site. Thus, the DH and MRF are important in mediating the DS effects of nicotine but not arecoline.