Showing papers on "Arecoline published in 2014"

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

Abstract: Areca nut is widely consumed by all ages groups in many parts of the world, especially south-east Asia The objective of this review is to systematically review and collate all the published data that are related to the systemic effects of areca nut The literature search was performed by an electronic search of the Pubmed and Cochrane databases using keywords and included articles published till October 2012 We selected studies that covered the effect of areca nut on metabolism, and a total of 62 studies met the criteria There is substantial evidence for carcinogenicity of areca nut in cancers of the mouth and esophagus Areca nut affects almost all organs of the human body, including the brain, heart, lungs, gastrointestinal tract and reproductive organs It causes or aggravates pre-existing conditions such as neuronal injury, myocardial infarction, cardiac arrhythmias, hepatotoxicity, asthma, central obesity, type II diabetes, hyperlipidemia, metabolic syndrome, etc Areca nut affects the endocrine system, leading to hypothyroidism, prostate hyperplasia and infertility It affects the immune system leading to suppression of T-cell activity and decreased release of cytokines It has harmful effects on the fetus when used during pregnancy Thus, areca nut is not a harmless substance as often perceived and proclaimed by the manufacturers of areca nut products such as Pan Masala, Supari Mix, Betel quid, etc There is an urgent need to recognize areca nut as a harmful food substance by the policy makers and prohibit its glamorization as a mouth freshener Strict laws are necessary to regulate the production of commercial preparations of areca nut

Arecoline-induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1

Abstract: Oral submucous fibrosis (OSF) is considered as a pre-cancerous condition of the oral mucosa and is highly associated with habitual areca quid chewing. Arecoline is the major alkaloid in areca quid and is thought to be involved in the pathogenesis of OSF. Our previous studies have demonstrated that arecoline could induce epithelial–mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts (BMFs). Therefore, we investigated the expression of zinc finger E-box binding homeobox 1 (ZEB1), which is a well-known transcriptional factor in EMT, in OSF tissues and its role in arecoline-induced myofibroblast transdifferentiation from BMFs. The expression of ZEB1, as well as the myofibroblast marker α-smooth muscle actin (α-SMA), was significantly increased in OSF tissues, respectively. With immunofluorescence analysis, arecoline induced the formation of α-SMA-positive stress fibres in BMFs expressing nuclear ZEB1. Arecoline also induced collagen contraction of BMFs in vitro. By chromatin immunoprecipitation, the binding of ZEB1 to the α-SMA promoter in BMFs was increased by arecoline. The promoter activity of α-SMA in BMFs was also induced by arecoline, while knockdown of ZEB1 abolished arecoline-induced α-SMA promoter activity and collagen contraction of BMFs. Long-term exposure of BMFs to arecoline induced the expression of fibrogenic genes and ZEB1. Silencing of ZEB1 in fibrotic BMFs from an OSF patient also suppressed the expression of α-SMA and myofibroblast activity. Inhibition of insulin-like growth factor receptor-1 could suppress arecoline-induced ZEB1 activation in BMFs. Our data suggest that ZEB1 may participate in the pathogenesis of areca quid–associated OSF by activating the α-SMA promoter and inducing myofibroblast transdifferentiation from BMFs.

Methylation-Associated Gene Silencing of RARB in Areca Carcinogens Induced Mouse Oral Squamous Cell Carcinoma

Abstract: Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.

The Hepatotoxicity and Testicular Toxicity Induced by Arecoline in Mice and Protective Effects of Vitamins C and E

Abstract: Arecoline is a major alkaloid of areca nuts which are widely chewed by southeast Asian and it manifests various toxic effects in different organs of human and animals. In this work, mature mice were treated by vitamins C plus E, arecoline, or both daily for four weeks. The results showed that arecoline significantly increased the levels of serum alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and significantly decreased the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in the liver tissues. Additionally, the body weight, testis weight, sperm counts, motility and normal sperms also were significantly decreased. The supplement of vitamins C and E can bring the activities of ALP and GPT to normal levels and partially restore the sperm counts compared to the arecoline-treated group but have no other positive effects. In conclusion, the vitamins C and E partially attenuated the arecoline-induced hepatotoxiciy but basically had on protective effects against the arecoline-induced testicular toxicity.

Arecoline is cytotoxic for human endothelial cells

Abstract: Background Oral submucous fibrosis is a pre-malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial–lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors. Materials and methods Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase-contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl-thiazol-tetrazolium assay. Results Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24-h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl-thiazol-tetrazolium assays. Conclusions Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis.

Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress

Abstract: Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma. The aim of the present work was to evaluate the impact of arecoline on human hepatic cytochrome P450 (CYP) enzymes in vitro and rat hepatic CYP enzymes, as well as the hepatic oxidative stress and liver injury of rats in vivo. The in vitro results indicated that arecoline hydrobromide (AH) has no significant effect on the activities of CYP2B, 2C9, 3A4, 1A2, 2E1 and 2D6 in human liver microsome (HLM). However, oral administration of AH at 4 and 20 mg/kg/d for seven consecutive days significantly increased the activities of rat hepatic CYP2B, 2E1, 2D, 3A, 2C and 1A2. In addition, AH at 100 mg/kg/d significantly increased the levels of ALT, AST and MDA, decreased the levels of SOD, CAT, GSH-Px and GSH, in rat liver. The in vivo induction of AH on rat hepatic CYP isoforms suggested that the high risk of metabolic interaction should be existed when the substrate drugs of the six kinds of CYP isoforms was administered in betel-quid use human. Furthermore, the in vivo results also suggested that AH-induced hepatoxicity should be associated with the induction of AH on rat hepatic CYP2E1 and 2B.

Arecoline inhibits epithelial cell viability by upregulating the apoptosis pathway: implication for oral submucous fibrosis.

Abstract: Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as a significant etiological factor for disease manifestation. However, the underlying molecular mechanisms regarding areca nut chewing-induced OSF are only partially understood. Herein, we reported that arecoline markedly induced morphologic change in HaCaT epithelial cells, but had no obvious effect on Hel fibroblast cells. MTS assay revealed that arecoline significantly suppressed HaCaT cell viability. Moreover, flow cytometric analysis indicated that arecoline substantially promoted HaCaT cell, but not Hel cell apoptosis in a dose-dependent manner. Furthermore, arecoline-induced HaCaT cell apoptosis was found to be associated with increased expression and activation of cleaved-Bid, cleaved-PARA and cleaved-caspase-3. Collectively, our results suggest that HaCaT epithelial cells are more sensitive than Hel fibroblast cells to arecoline-induced cytotoxicity, which may be involved in the pathogenesis of OSF.

The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

Abstract: Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

Increased expression of carbonic anhydrase IX in oral submucous fibrosis and oral squamous cell carcinoma.

Abstract: BACKGROUND Cumulative evidence has demonstrated that carbonic anhydrase IX (CAIX) is upregulated in many types of human cancers. We attempted to evaluate plasma levels of CAIX in patients with oral cancer and investigated whether plasma CAIX is correlated with the progression of this disease. METHOD In total, 191 patients with oral cancer, 30 patients with oral submucous fibrosis and 100 controls were recruited in this study. The plasma samples were collected and the levels of soluble CAIX in plasma were determined by the enzyme-linked immunosorbent assay (ELISA). Furthermore, the normal buccal mucosa fibroblast was challenged by arecoline, the major areca nut alkaloid, to assess the relationship between the levels of CAIX and areca nut chewing in oral cancer patients. RESULTS Results showed that patients with oral cancer exhibited significantly higher levels of soluble CAIX compared to controls (p<0.001). Plasma levels of CAIX in oral cancer patients were associated with clinical stages after adjusting for age and areca nut chewing (p<0.05). In addition, patients with areca nuts chewing had higher CAIX levels than those who have not chewed areca nuts. Total carbonic anhydrase activity and CAIX mRNA levels were significantly higher in oral submucous fibrosis fibroblasts than in normal buccal mucosa fibroblasts. Moreover, arecoline elevated CAIX expression in a dose-dependent manner in normal buccal mucosa fibroblasts. CONCLUSIONS Our results suggest that determining plasma levels of CAIX may be used as a non-invasive method for monitoring oral cancer progression and the involvement of areca quid chewing in oral carcinogenesis may be related to a higher expression of CAIX.

Betel Chewing and Arecoline Affects Eotaxin-1, Asthma and Lung Function

Abstract: Background Betel nut is commonly used in many countries. Despite evidence suggesting an association with asthma, few studies have investigated the connection between betel nut use and asthma; thus, the underlying mechanism for the association with asthma is also unclear. The aim of this study was to investigate the association between betel chewing and asthma as well as the associations of plasma arecoline (a biomarker for exposure) and eotaxin-1 (a potential mediator) with asthma and lung function. Methods We recruited 600 hospital-based asthmatic patients and 1200 age- and gender-matched community controls in southern Taiwan. To clarify the mechanism of action for eotaxin-1 in the association between betel chewing and asthma, we also designed an in vitro experiment to study the functional associations between arecoline exposure and eotaxin-1 levels. Results A significant association was found between asthma and current betel chewing (adjusted odds ratio 2.05, 95% CI = 1.12–3.76), which was independent of potential confounders but was attenuated following adjustment for eotaxin-1. Arecoline and eotaxin-1 levels were positively correlated (Spearman r = 0.303, p = 0.02), while arecoline and arecaidine were negatively correlated with lung function. Functionally, arecoline alone does not induce eotaxin-1 release in vitro from dermal and gingival fibroblasts. However, in the presence of IL-4 and TNF-alpha, arecoline at 100 μg/ml induced more eotaxin-1 release than arecoline at 0 μg/ml (2700±98 pg/ml vs 1850±142 pg/ml, p = 0.01 in dermal fibroblast cells, and 1489±78 pg/ml vs 1044±95 pg/ml, p = 0.03 in gingival fibroblast cells, respectively). Conclusion Betel chewing is associated with asthma in this population, with arecoline induction of eotaxin-1 supported as a plausible causal pathway.

Cystatin C: Its role in pathogenesis of OSMF

Abstract: Oral Submucous Fibrosis (OSF) is a chronic disorder characterized by fibrosis of the mucosa lining the upper digestive tract involving the oral cavity, oro- and hypopharynx and the upper third of the oesophagus. The alkaloids from areca nut are the most important chemical constituents biologically, in producing this lesion. These chemicals appear to interfere with the molecular processes of deposition and/or degradation of extracellular matrix molecules such as collagen. Increased collagen synthesis or reduced collagen degradation have been considered as a possible mechanism in the development of the disease. Increased and continuous deposition of extracellular matrix may also take place as a result of disruption of the equilibrium between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMP). Arecoline a product of areca nut was found to elevate Cystatin C mRNA (CST3) and protein expression in a dose-dependent manner. Cystatin C expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. Cross-links between the molecules are essential for the tensile strength of collagen fibres. These areas are resistant to attack by collagenases but can be attacked by a number of other serine and cysteine proteinases. CST3 encoding a cysteine proteinase inhibitor might contribute to the stabilization of collagen fibrils in OSMF. Treatment directed against Cystatin C may serve as a novel treatment for submucous fibrosis and also in preventing its transformation into malignancy.

A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India.

Abstract: The susceptibility of an individual to oral cancer is mediated by genetic factors and carcinogen-exposure behaviors such as betel quid chewing, tobacco use, and alcohol consumption. This pilot study was aimed to identify the genetic alteration in 100 bp upstream and downstream flanking regions in addition to the exonic regions of 169 cancer-associated genes by using Next Generation sequencing with aim to elucidate the molecular pathogenesis of tobacco- and betel quid-associated oral cancer of Northeast India. To understand the role of chemical compounds present in tobacco and betel quid associated with the progression of oral cancer, single nucleotide polymorphisms (SNPs) and insertion and deletion (Indels) found in this study were analyzed for their association with chemical compounds found in tobacco and betel quid using Comparative Toxogenomic Database. Genes (AR, BRCA1, IL8, and TP53) with novel SNP were found to be associated with arecoline which is the major component of areca nut. Genes (BARD1, BRCA2, CCND2, IGF1R, MSH6, and RASSF1) with novel deletion and genes (APC, BRMS1, CDK2AP1, CDKN2B, GAS1, IGF1R, and RB1) with novel insertion were found to be associated with aflatoxin B1 which is produced by fermented areca nut. Genes (ADH6, APC, AR, BARD1, BRMS1, CDKN1A, E2F1, FGFR4, FLNC, HRAS, IGF1R, IL12B, IL8, NBL1, STAT5B, and TP53) with novel SNP were found to be associated with aflatoxin B1. Genes (ATM, BRCA1, CDKN1A, EGFR, IL8, and TP53) with novel SNP were found to be associated with tobacco specific nitrosamines.

Arecoline induces TNF-alpha production and Zonula Occludens-1 redistribution in mouse Sertoli TM4 cells

Abstract: Arecoline, a major alkaloid in Areca nut has the ability to induce oxidative stress. The effect of Areca nut, arecoline on reducing sperm quality and quantity were documented previously using several animal models. Junction disruption by down-regulation of the junction-adhesive protein via oxidative stress is an important route mediating abnormal spermatogenesis. Therefore, in this present study, we investigated the functional role of arecoline on junctional proteins. To analyze direct effects of arecoline on testis cells, confluent mouse testicular Sertoli cell line TM4 was exposed to arecoline. Arecoline decreased insoluble zonula occludens-1 (ZO-1) protein expression in TM4 cells, however, arecoline treatment increased TNF-alpha production in both TM4 and monocytic THP1 cells. In addition, ERK1/2 inhibitor PD98059 reversed arecoline effects on TNF-alpha and ZO-1. Arecoline increases the production of TNF-alpha and induces protein redistribution of ZO-1. All these results explain the role of arecoline in male reproductive dysfunction, besides its cytotoxic induction.

Expression of a Splice Variant of CYP26B1 in Betel Quid-Related Oral Cancer

Abstract: Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.

The role of arecoline on hepatic insulin resistance in type 2 diabetes rats

Abstract: OBJECTIVE To explore the effects of arecoline on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism. METHODS Forty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model. rats were randomly divided into 5 groups (n = 8): control group, model group and model group were treated with different dose (0, 0.5, 1, 5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot. RESULTS 1.5 mg/kg arecoline could significantly decrease the level of fasting blood glucose, blood lipid, blood insulin level and liver G6Pase, PEPCK, IL-6, TNF-alpha mRNA level in type 2 diabetes rats. 1.5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression. CONCLUSION Arecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the creased glucose metabolism and inflammation related genes expression.

Stimulation of endothelial non-neuronal muscarinic receptor attenuates the progression of atherosclerosis via inhibiting endothelial cells activation.

Abstract: Objective To investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation. Methods Atherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining. The gene expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-κB activity were detected by Western blot analysis. NO production, MCP-1 secretion in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium adhesion assay were also performed after arecoline treatments. Results Arecoline efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated the IκB-α degradation and P65 phosphorylation in the aortae of ApoE-/- mice. Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine methylester could abrogate these effects. Arecoline also significantly inhibited the adherence of U937 monocytes to the ox-LDL injured human umbilical vein endothelial cells, which could be abolished by atropine. Conclusion Our results indicate that arecoline attenuates the progression of atherosclerosis and inhibits endothelial cells activation and adherence by stimulating endothelial NNMR. These effects, at least in part, are due to its modulation on NF-κB activity.

Areca fruit total phenol extractive as well as preparation method and application thereof

Abstract: The invention discloses an areca fruit total phenol extractive as well as a preparation method and the application of the areca fruit total phenol extractive. The preparation method of the areca fruit total phenol extractive comprises the steps of smashing areca fruit, sufficiently extracting phenolic substances in the areca fruit by taking an organic solvent as an extraction agent in the manner of ultrasound-microwave synergistic extraction, and carrying out systematic separation on the areca fruit extractive in combination with macroporous polymeric adsorbent column chromatography to effectively eliminate the alkaloid with carcinogenicity such as the arecoline and the like so as to obtain the AFTP (areca fruit total phenol extractive). The animal experiment shows that the areca fruit total phenol extractive has prominent antagonism to the depression, the areca fruit total phenol extractive is wider in adaptation disease in the antidepressant effect and is free from any side effects compared with the existing antidepressant which has single function mechanism on the clinic, and the novel drug resources and the corresponding drug preparation are provided for prevention and treatment of depression.

Oral submucous fibrosis: a review article on

Abstract: Areca quid chewing related oral mucosal lesions are potential hazard to a large population worldwide. Commercially freeze dried products such as pan masala, guthka and mawa have high concentration of areca nut per chew and appear to cause OSMF more rapidly than by self prepared conventional betel quid that contain smaller amounts of areca nut. The basic constituent of areca nut is either raw or dried or boiled or baked. Diverse agents including lime, tobacco, catechu, cloves, saffron and leaf of piper betel leaves may form a part of formulation. Many of the undesirable aspects of areca nut have been attributed to arecoline. These chemical appear to interfere with the molecular processes of deposition and or degradation of extracellular matrix molecules such as collagen, causing imbalance in the normal process. The most likely events that take place with regards to the above imbalance may be reduced phagocytosis of collagen by fibroblasts, up or down regulation of copper dependent enzyme lysyl oxidase, matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases . It has been postulated that areca nut may also induce the development of the disease by increased levels of cytokines in the lamina propria. Current evidence implicates collagen related genes in susceptibility and pathogenesis of OSMF. The individual mechanisms operating at various stages of the disease- initial, intermediate and advanced–need further study in order to propose appropriate therapeutic interventions.

Insecticidal Activity of Areca catechu Ethanol Extract against House Dust Mite

Abstract: In this study, the insecticidal effect of the ethanol extract of Areca catechu against the house dust mite, Der-mtophagoides pteronysinus, was examined. Ethanolic Areca catechu extract was directly applied at different concen-trations (1.0, 0.5, 0.25, 0.125, 0.0625 mg/40 µl) and then allowed an exposure of 24 hours. The 1.0 mg/40 µl and 0.5 mg/40 µl concentrations of Areca catechu ethanol extract produced mortality rates of 100% and 98%, respectively, againsthouse dust mite, Dermtophagoides pteronysinus. Areca catechu ethanol extract at a concentration of 0.125 mg/40 µlproduced a 50% insecticidal effect. These results proved the insecticidal effect of Areca catechu ethanol extract againsthouse dust mite, Dermtophagoides pteronysinus. To check for the presence of the recognized insecticidal arecoline andmonoterpene compounds in Areca catechu, gas chromatography-mass spectrometry and thermal desorption-gas chro-matography/mass spectrometry were performed. As a result, arecoline and ten monoterpene compounds were identi-fied in Areca catechu.Keywords: insecticidal effect, house dust mite, Areca catechu, ethanol extract, gas chromatography-mass spectrometry,thermal desorption-gas chromatography/mass spectrometry

Arecoline induces TNF-alpha production and Zonula Occludens-1 redistribution in mouse

Abstract: Background: Arecoline, a major alkaloid in Areca nut has the ability to induce oxidative stress. The effect of Areca nut, arecoline on reducing sperm quality and quantity were documented previously using several animal models. Junction disruption by down-regulation of the junction-adhesive protein via oxidative stress is an important route mediating abnormal spermatogenesis. Therefore, in this present study, we investigated the functional role of arecoline on junctional proteins. Results: To analyze direct effects of arecoline on testis cells, confluent mouse testicular Sertoli cell line TM4 was exposed to arecoline. Arecoline decreased insoluble zonula occludens-1 (ZO-1) protein expression in TM4 cells, however, arecoline treatment increased TNF-alpha production in both TM4 and monocytic THP1 cells. In addition, ERK1/2 inhibitor PD98059 reversed arecoline effects on TNF-alpha and ZO-1. Conclusions: Arecoline increases the production of TNF-alpha and induces protein redistribution of ZO-1. All these results explain the role of arecoline in male reproductive dysfunction, besides its cytotoxic induction.

Synthetic or Imitation Nicotine Compositions, Processes and Methods of Manufacture

Abstract: Processes and methods of manufacturing a synthetic or imitation nicotine product are provided. One process may include the steps of providing a plurality of areca fruits, drying the plurality of areca fruits, dehusking the plurality of areca fruits to obtain a plurality of areca nuts, chopping, shredding or grinding the plurality of areca nuts into a multiplicity of areca nut particles, introducing the multiplicity of areca nut particles into a tank containing water, agitating the multiplicity of areca nut particles to create a slurry, determining an amount of arecoline in the slurry and pumping the water having the predetermined amount of arecoline through a filter and into a holding tank and evaporating the arecoline from the water. An imitation nicotine product that may include 1% to 20% arecoline by weight with other elements may then be manufactured.

Traditional Chinese Treatment of Taeniasis

Abstract: Human taeniasis is infection of adult Taenia solium and Taenia saginata, but both clinical manifestations are similar. Taenia infection was serious and widespread in ancient China. Chinese people had paid long attention to taeniasis in ancient medical books and tried to eliminate the infection by means of traditional Chinese medicine (TCM). Some TCM against taeniasis are summarized referring to both the historical literature and recent modern results of research in this chapter. Omphalia lapidescens, Agrimonia pilosa, Semen moschatae, and Areca catechu are involved in the anthelmintic TCM. The origin, preparation, and use of the medical plants, their known chemical components, as well as their possible pharmaceutical functions and the anthelmintic mechanisms were introduced. The dried sclerotes of Omphalia lapidescens are ground into powder when used as medicine. Omphalia proteinase is the most effective ingredient in natural O. lapidescens. Its proteolysis is able to break down the proteins of the parasitic tapeworms. Experiments have shown that the proteolysis of the parasitic proteins may induce the anthelmintic activity of O. lapidescens. Agrimonia pilosa is a perennial herb. The clean dried whole plant is prepared for medical use. Each time 30–60 g dried herbs are boiled with water to produce a lotion for orally uptake (The herbal decoction). Agrimophol is the most effective ingredient of A. pilosa. The anthelmintic activity of agrimophol may owe more to direct killing effect than through the nervous system way. Semen moschatae is the dried seed of Cucurbita moschata and is commonly known as pumpkin seed. The pharmacological efficacy of pumpkin seed is not very potent, and thus it is generally combined with Areca seed for expelling tapeworms. When the therapy begins, the infected person should eat raw pumpkin seeds 150 g on an empty stomach first, then drink the prepared liquid decoction of Areca 300 ml (100 g dried Areca seeds are boiled in water to yield 300 ml decoction in advance). Half an hour later, the adult patient should ingest 60 ml of 50 % bitter salt followed by plenty of water (1,000–2,000 ml) to finish the treatment. Areca seed is the dried seed of Areca catechu. Four alkaloids (arecoline, arecaidine, guvacine, and guvacoline) in Areca seeds are most important biological components to kill the parasite. A recent study suggested that arecoline might cause nervous paralysis of cestodes as well as inhibit the acetylcholinesterase activity. These findings may explain why Areca seeds can paralyze the worms in the small intestine and then expel parasites from host’s intestine. In brief, TCM have been proved to be very successful in the fight against parasites, and many of them are still in use today.