Showing papers on "Arecoline published in 2011"
TL;DR: The data suggest that the pathogenesis of OSF may be epithelial‐driven and involve arecoline‐dependent up‐regulation of αvβ6 integrin, raising the possibility that this mechanism may support malignant transformation.
Abstract: Oral submucous fibrosis (OSF) is a premalignant, fibrosing disorder of the mouth, pharynx, and oesophagus, with a malignant transformation rate of 7-13%. OSF is strongly associated with areca (betel) nut chewing and worldwide, over 5 million people are affected. As αvβ6 integrin is capable of promoting both tissue fibrosis and carcinoma invasion, we examined its expression in fibroepithelial hyperplasia and OSF. αvβ6 was markedly up-regulated in OSF, with high expression detected in 22 of 41 cases (p < 0.001). We investigated the functional role of αvβ6 using oral keratinocyte-derived cells genetically modified to express high αvβ6 (VB6), and also NTERT-immortalized oral keratinocytes, which express low αvβ6 (OKF6/TERT-1). VB6 cells showed significant αvβ6-dependent activation of TGF-β1, which induced transdifferentiation of oral fibroblasts into myofibroblasts and resulted in up-regulation of genes associated with tissue fibrosis. These experimental in vitro findings were confirmed using human clinical samples, where we showed that the stroma of OSF contained myofibroblasts and that TGF-β1-dependent Smad signalling was detectable both in keratinocytes and in myofibroblasts. We also found that arecoline, the major alkaloid of areca nuts, up-regulated keratinocyte αvβ6 expression. This was modulated through the M(4) muscarinic acetylcholine receptor and was suppressed by the M(4) antagonist, tropicamide. Arecoline-dependent αvβ6 up-regulation promoted keratinocyte migration and induced invasion, raising the possibility that this mechanism may support malignant transformation. Over 80% of OSF-related oral cancers examined had moderate/high αvβ6 expression. These data suggest that the pathogenesis of OSF may be epithelial-driven and involve arecoline-dependent up-regulation of αvβ6 integrin.
90 citations
TL;DR: The findings suggest that these phytochemicals can replace the commercial drugs in part, which could lead to a reduction in toxicity and side effects caused by the later as well as reduce the secondary complications.
43 citations
TL;DR: The data showed for the first time that ANe-induced miR-23a was correlated with a reduced FANCG expression and DSB repair, which might contribute to ANE-associated human malignancies.
43 citations
TL;DR: It is interesting to find that the major metabolite of are coline, arecoline N-oxide, is moderately mutagenic to these Salmonella tester strains, which might induce damage in human oral tissues and cause mutagenicity inSalmonella typhimurium tester strain TA 100 and TA 98.
Abstract: The areca nut is the most widely consumed psychoactive substance in Taiwan, India, and Southeast Asia. It is considered to be an environmental risk factor for the development of oral submucous fibrosis and cancer. Arecoline, the major alkaloid of areca nut, has been known to cause cytotoxicity and genotoxicity in various systems. However, the active compound accounting for arecoline-induced damage in normal human oral cells is still uncharacterized. The present study was undertaken to identify the active metabolite of arecoline that might induce damage in human oral tissues and cause mutagenicity in Salmonella typhimurium tester strains TA 100 and TA 98. It is interesting to find that the major metabolite of arecoline, arecoline N-oxide, is moderately mutagenic to these Salmonella tester strains. This mutagenicity was potently inhibited by sulfhydryl compounds, namely, glutathione, N-acetylcysteine, and cysteine, whereas methionine is inactive in this inhibition. The mutagenicity of arecoline N-oxide was strongly inhibited by the N-oxide reducing agent titanium trichloride. The possible role of arecoline N-oxide in the induction of oral carcinogenesis by areca nut chewing is discussed.
35 citations
TL;DR: Results suggest that arecoline may inhibit AMPK through intracellular ROS, responsible for the execution of apoptosis.
32 citations
TL;DR: It is demonstrated that, in HUVECs, arecoline stimulates ROS production and ICAM and VCAM expression and HO-1 expression is also upregulated through the ROS, tyrosine kinase, and MAPK signaling pathways.
32 citations
TL;DR: Findings indicated that fenofibrate reduced the tumor incidence rate and suppressed the tumor progression into SCC and that these molecular events might be linked to the EGFR and COX2 regulatory pathways.
31 citations
TL;DR: It is found that betel nut extract and arecoline blocked lipid storage in 3T3-L1 adipocytes and have diabetogenic potential on adipocytes that may result in insulin resistance and diabetes at least in part via the obstruction of insulin signaling and the blockage of lipid storage.
Abstract: According to several population-based studies, betel nut chewing is associated with metabolic syndrome and diabetes in British South Asians and Taiwanese. However, the underlying molecular mechanism is not yet clear. Arecoline is an alkaloid-type natural product found in betel nuts. Our aim was to clarify the influence of betel nut extract and arecoline on lipid accumulation and insulin signaling in adipocytes. We found that betel nut extract and arecoline blocked lipid storage in 3T3-L1 adipocytes. The possible mechanism may function by inhibiting the expression of the insulin receptor, glucose transporter-4, fatty acid synthase, and the lipid droplet proteins perilipin and adipophilin. In addition, betel nut extract and arecoline increased the basal level of IRS-1 serine307 phosphorylation and decreased insulin-stimulated IRS-1 tyrosine, Akt, and PI3 kinase phosphorylation. In conclusion, betel nut extract and arecoline have diabetogenic potential on adipocytes that may result in insulin resistance and diabetes at least in part via the obstruction of insulin signaling and the blockage of lipid storage.
29 citations
TL;DR: This study suggests that inhibition of IL-8 and RANTES orIL-8/RANTES-mediated mitogen-activated protein kinase/KLF5 signaling is an attractive therapeutic target for areca nut-induced asthma.
27 citations
TL;DR: It is suggested that arecoline is toxic to mouse embryos as early as peri-implantation stages in mice, and improved understanding of the effects of are coline during embryogenesis may help to establish public health policies and to develop potential treatments for such patients.
22 citations
TL;DR: It is demonstrated that HSP47 expression is significantly upregulated in areca quid chewing-associated OSCCs and could be used clinically as a marker for lymph node metastasis of oral carcinogenesis.
Abstract: J Oral Pathol Med (2010) 40: 390–396
Background: Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression.
Methods: Thirty-two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N-acetyl-l-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, cyclooxygenase-2 inhibitor NS-398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms.
Results: HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P 0.05). The lower HSP47 expression was associated with lymph node metastasis (P = 0.015). Arecoline was found to elevate HSP47 expression in a dose- and time-dependent manner (P < 0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A markedly inhibited the arecoline-induced HSP47 expression (P < 0.05).
Conclusion: Our findings demonstrated that HSP47 expression is significantly upregulated in areca quid chewing-associated OSCCs. HSP47 could be used clinically as a marker for lymph node metastasis of oral carcinogenesis. In addition, arecoline-induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A.
TL;DR: The findings provide the first evidence that regular use of arecoline may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders associated with prostate enlargement.
01 Jan 2011
TL;DR: It is known to improve concentration and relaxation, with other reported effects including lifting of mood, a sense of well-being, heightened alertness, staving off hunger, aphrodisiac properties and as postprandial digestant.
Abstract: The habit of chewing areca has been mentioned in the Sanskrit manuscripts and used as food, medicine, social and religious purposes. The word ‘Areca’ is derived from the Malay word adakka or from adakeya, the Indian equivalent. Areca nut is the fourth most commonly used social drug, ranking after nicotine, ethanol and caffeine. Areca preparations and specific ingredients vary by cultural group and individual user. Areca nut taken along with tobacco is known to have a deleterious effect of the oral cavity to the extent of causing oral cancer. However, not much is documented regarding the advantages of chewing areca nut. Arecoline, the principal alkaloid in areca nut, acts as an agonist primarily at muscarinic acetylcholine receptors and stimulates the central and autonomic nervous system. This leads to subjective effects of increased well-being, alertness and stamina. It is known to improve concentration and relaxation, with other reported effects including lifting of mood, a sense of well-being, heightened alertness, staving off hunger, aphrodisiac properties and as postprandial digestant. It has also been shown to have cariostatic property. Areca nut also exerts a direct antimicrobial effect against bacteria, including Streptococcus mutans, Streptococcus salivarius and various other micro organisms in the oral cavity. This article reviews the various possible favourable effects of chewing areca nut on the oral and general health.
TL;DR: The modifications of mouse motility and of the levels of acetylcholine in two sections of the CNS caused by a chronic administration of arecoline for 20 days have been studied.
Abstract: — The modifications of mouse motility and of the levels of acetylcholine (ACh) in two sections of the CNS caused by a chronic administration of 4.5; 9.5; 28.5 and 60 mg kg-−1 day−1 of arecoline for 20 days have been studied. At low doses (4.5 and 9.5 mg kg−1 day−1), arecoline caused no modification of the ACh levels and of the motility. The higher doses (28.5 and 60 mg kg−1 day−1) caused a reduction of the mouse motility and an increase of the ACh levels in the subcortical structures of the CNS of the mouse.
TL;DR: There is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB, as measured by calculating a unidirectional blood‐to‐brain transfer constant for the circulating tracer [14C]‐α‐aminoisobutyric acid.
Abstract: The aim of the present study was to investigate the existence of alterations of the blood-brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg-1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg-1) was injected i.p. into methylatropine-pretreated rats, it induced a significant decrease of Ki values within the frontal cortex, parietal cortex, striatum and brain-stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB.
TL;DR: It is shown that arecoline, a main alkaloid found in AN, stimulated Cyr61 synthesis in human gingival epithelial S-G cells and Lovastatin completely inhibited are coline-induced Cyr 61 synthesis and the inhibition is dose-dependent.
TL;DR: This article showed that polyphenols enhanced the development of myeloid-derived suppressor cells in vivo, which may be a critical mechanism linking inflammation and compromised immunity reported to be associated with the pathophysiology of areca-related oral diseases.
Abstract: J Oral Pathol Med (2011) 40: 769–777
Background: Areca quid chewing is an etiological factor contributing to the development of oral cancer and pre-cancers, whose pathophysiology has been linked to inflammation and immune deterioration. Myeloid-derived suppressor cells (MDSC) play a key role in the regulation of immunity under certain pathological conditions, such as inflammation and cancer. As areca nut extracts (ANE) have been reported to induce a proinflammatory effect in antigen-stimulated mice, we hypothesized that ANE might enhance the development of MDSC.
Methods: Ovalbumin (OVA)-sensitized BALB/c mice were daily administered with ANE (5–50 mg/kg), polyphenol-enriched ANE (PANE; 25 mg/kg) or arecoline (5 mg/kg) by intraperitoneal injection for 10 doses. The mouse footpads were then subcutaneously challenged with OVA to induce local inflammatory responses.
Results: ANE and PANE treatment significantly increased the spleen index and the population of CD11b+Gr-1+ cells in the spleen and peripheral blood, whereas arecoline was inactive. In addition, ANE and PANE treatment enhanced the expression of cytokines and enzymes associated with the immunosuppressive function of MDSC, including IL-10, arginase-I and iNOS in splenic CD11b+ cells. Concordantly, ANE and PANE treatment augmented the infiltration of Gr-1+IL-10+ cells in the footpads challenged with OVA.
Conclusions: Our results suggested that areca nut constituents, in particular, polyphenols enhanced the development of myeloid-derived suppressor cells in vivo, which may be a critical mechanism linking inflammation and the compromised immunity reported to be associated with the pathophysiology of areca-related oral diseases.
TL;DR: Some evidence suggests that betel nut extract may improve speech, bladder control, and muscle strength after cerebrovascular accidents or stroke, but high doses of its usage can cause hypercalcemia, hypokalemia, and metabolic alkalosis.
Abstract: Publisher Summary This chapter describes important information about betel nut use and its effects on health. Betel nut is a seed of the Areca catechu tree, cultivated in tropical humid regions. Up to 20% of the world's population uses betel nut—more so in South and Southeast Asia but medical use of betel nut is limited. It is the fourth most widely used addictive substance in the world, after caffeine, nicotine, and alcohol. People chew it for stress reduction, for a feeling of well-being, and for heightened awareness. It contains several psychoactive compounds. Arecoline, the principal alkaloid in betel nut, acts as a stimulant of the nervous system and increases the levels of noradrenaline and acetylcholine. This leads to subjective effects of increased well-being, alertness, and stamina. The preferred route of intake is chewing, which leads to rapid absorption of these alkaloids through the buccal mucosa. It has also been suggested that betel nut chewing may confer protection against dental caries. The cariostatic properties of betel nut are not well known, but it has been suggested that the betel stain, which often coats the surface of the teeth, may act as a protective varnish. In vitro evidence has suggested that the tannin content of areca may have antimicrobial properties, and this may contribute to the cariostatic role of areca. Some evidence suggests that betel nut extract may improve speech, bladder control, and muscle strength after cerebrovascular accidents or stroke. However, betel nut chewing can produce significant cholinergic, neurological, cardiovascular, and gastrointestinal manifestations. High doses of its usage can cause hypercalcemia, hypokalemia, and metabolic alkalosis.
TL;DR: It is found that the activity of the arecolinium ion on the guineapig ileum was 1.4 times as great as carbachol and had a similar slope and maximum and it was also about equal to acetylcholine although differing in slope.
Abstract: 0.034 1.39 Guinea-pig ileum . . . . 1 Frog rectus abdominis 1.42 0.01 1 The comparative activity of arecoline and arecoline N-metho salt SrR,-Arecoline is well known as one of the relatively few tertiary amines that have high activity as a muscarinic agent. Indeed this activity has been underestimated in the past because the pKa of arecoline is 7.61 (35\") so that it is incompletely ionised at blood pH and even more so in Ringer-Locke or Tyrode's. Recently, we have found that the activity of the arecolinium ion on the guineapig ileum was 1.4 times as great as carbachol and had a similar slope and maximum and it was also about equal to acetylcholine although differing in slope. We thought it of interest to see whether the quaternary arecolinium N-metho salt (the methiodide prepared by the method of Wilstatter, 1887) had an even greater activity. However, it was only one fortieth of the activity of the tertiary arecolinium ion itself. On the other hand, when tested on the frog rectus abdominis, the tertiary arecolinium ion had only 1.1% of the activity of carbachol whereas the quaternary N-metho salt was a little more active than carbachol (Table 1).
TL;DR: OL plus arecoline can play a synergistic role in enhancing hypolipidemia in rats according to the level of total cholesterol, triglyceride, high density lipoprotein cholesterol, arteriosclerosis index and HDL-C.
Abstract: Both Areca nut oil (OL) and arecoline play some roles in moderating hypolipidemia but the pathways may be different. The authors hypothesize OL plus arecoline can lead to an improved hypolipidemia in animal model. In this study, the fed rats with series doses of OL alone or OL plus arecoline. The gaining weight, the level of total cholesterol (TC), triacylglyceride (TG), high density lipoprotein cholesterol (HDL-C) and arteriosclerosis index (AI) from the rats were then examined. The authors found low dose of OL (0.335 g·kg-1) plus arecoline (3 mg·kg-1) could significantly reduce the level of TC and AI, and increase the level of HDL-C compared to other groups. They conclude OL (0.335 g·kg-1) plus arecoline (3 mg·kg-1) can play a synergistic role in enhancing hypolipidemia in rats.
Key words: Areca nut oil, total cholesterol, triglyceride, high density lipoprotein cholesterol, arteriosclerosis index.
TL;DR: The present results support an increased cardiovascular responsiveness to central cholinergic stimulation in the genetically epilepsy‐prone rat which appears to be related to a pre‐synaptic rather than a post-synaptic component.
Abstract: We sought to determine whether differences in cardiovascular responsiveness to central stimulation of the cholinergic system existed between the genetically epilepsy-prone and outbred Sprague-Dawley rats. We treated the unanaesthetized, restrained rats with the indirect cholinergic agonist physostigmine (25, 50, 100 and 200 micrograms kg-1, i.v.) and the direct muscarine agonist arecoline (50, 100 and 200 micrograms kg-1, i.v.). Blood pressure and heart rate were evaluated. Genetically epilepsy-prone rats demonstrated to be more susceptible to the action of physostigmine than the outbred Sprague-Dawley rats. Conversely, we did not note any difference between the two strains in the extent of the pressor response induced by arecoline. Moreover, we treated both strains with hemicholinium-3 (34.8 nmol, i.c.v.) to deplete endogenous stores of acetylcholine. This treatment did not affect the pressor response to arecoline, whereas it greatly reduced the response to physostigmine. The present results support an increased cardiovascular responsiveness to central cholinergic stimulation in the genetically epilepsy-prone rat which appears to be related to a pre-synaptic rather than a post-synaptic component.
Journal Article•
TL;DR: Arecoline is able to induce Hacat cell apoptosis, which may contribute to the development of oral submucous fibrosis.
Abstract: Objective To observe the effect of arecoline on the apoptosis of Hacat cellsMethods Hacat cells were incubated with different concentrations of arecoline(0,25,50,75,100 or 125 μg/mL) for 24 hDNA fragments and apoptosis were examined by agarose gel electrophoresis and flow cytometry,respectivelyResults DNA fragments were obviously observed in groups treated with arecoline in a concentration of 100 or 125 μg/mLThe results of flow cytometry showed that arecoline induced apoptosis in a dosedependent mannerConclusion Arecoline is able to induce Hacat cell apoptosis,which may contribute to the development of oral submucous fibrosis
Journal Article•
TL;DR: In this paper, the authors used response surface methodology (RSM) to fit a quadratic polynomial regression model as a response to three independent variables which had significant effects on the arecoline yield.
Abstract: Arecoline was obtained with the methods of microwave pretreatment- supercritical CO2 fluid extraction from areca nut. The content of the arecoline which was used as evaluating criteria, was determined by HPLC. Based on the results of single factor experiments, using response surface methodology(RSM) to fit a quadratic polynomial regression model as a response to three independent variables which had significant effects on the arecoline yield. Results showed that the yield of arecoline under microwave pretreatment could improve obviously, the optimal values of technological parameters was as follows: the extraction pressure was 33 MPa; the extraction temperature was 63 ℃; the microwave power was 480 W. Under such conditions, the yield of arecoline was up to (0.448±0.007)% (n=3), which was very close to the predicted value of 0.452%.
TL;DR: The results provide information regarding the molecular mechanisms of areca nut-induced oral carcinogenesis and revealed Ches1 was down regulation upon arecoline treatment.
Abstract: Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL
Oral cancer is the 6th most frequent cancer in Taiwan. The habit of areca nut chewing is the main etiological factor of oral cancer. To shed light on molecular basis of areca nut associated oral carcinogenesis, we established two oral cell sublines chronically treated with areca nut extract (ANE) at IC70 dose for 2 months. Affymatrix microarray was used in transcriptome profiling between parental and ANE sublines of oral cancer cells. Algorithmic analysis was applied to analyze the network regulatory pathways. RT-PCR was used to validate the genes altered expressions in ANE-sublines. Total of 35 genes was differentially expressed in both sublines. Several functional pathways were apparently altered, with lipid metabolism (P=1.95×10−10), oxidative phosphorylation (P=1.02×10−6), and cell adhesion (P=9.66×10−6) most significant. Seven genes were confirmed over 2-fold of changes, including HMGCS1, KRT-17 up-regulation and SMC4, CENPF, ID-1, IL1-alpha and Ches1 down-regulation. Further study revealed Ches1 was down regulation upon arecoline treatment. Consistently, this gene was reduced expression in 52% of oral cancer tissues, which was significantly correlated with areca nut chewing habit of patients (p = 0.04). Thus, these results provide information regarding the molecular mechanisms of areca nut-induced oral carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 26. doi:10.1158/1538-7445.AM2011-26
TL;DR: It would be important to advise pregnant women against the consumption of areca nut in any of its forms, as along with adverse outcomes, the presence of arecoline has been studied not only in pregnant women but also in neonatal biological matrices as meconium, cord blood and urine.
Abstract: Betel nut is commonly used in a "social" manner in Asian countries, including pregnant women, because of its antiemetic effects. The adverse outcomes in newborns such as neonatal withdrawal syndrome and low birth weight and length have been described in various reports. The aim of our review was to gather the information that has been described until now on behalf of betel nut use during pregnancy and possible deleterious effects on newborns. A research on PubMed was carried out searching "arecoline and newborn" and "areca nut and newborn". The main results of our revision were that along with adverse outcomes, the presence of arecoline has been studied not only in pregnant women but also in neonatal biological matrices as meconium, cord blood and urine. Therefore it would be important to advise pregnant women against the consumption of areca nut in any of its forms.