Therapeutic potential of sulforaphane: modulation of NRF2 mediated PI3/AKT/mTOR pathway in oral fibrosis / Potencial terapêutico do sulforafano: modulação do NRF-2 mediado o pela via PI3/AKT/mTOR na fibrose oral

Oral Submucous Fibrosis is a potentially malignant disorder caused by habitual areca nut chewing, which contributes to the dispersion of active alkaloids into subepithelial tissues, stimulating excessive extracellular matrix deposition. Various treatment modalities are available; however, their efficacy in inhibiting fibrosis progression remains limited. Sulforaphane (SFN), an isothiocyanate found abundantly in cruciferous plants, is known to have effective antifibrotic properties. Objective: The present study investigated the antifibrotic effect of SFN via phosphatidylinositol 3 kinase (PI3K), Serine/Threonine Kinase 1 (AKT-1), mammalian target of rapamycin (mTOR) pathway in arecoline (AER) induced fibrosis in human gingival fibroblasts [HGFs]. Material and Methods: MTT assay determined the half-maximal inhibitory concentration of AER and SFN at 24h in the HGF cell line. Expression levels of transforming growth factor ß1 (TGFß1), collagen type 1 alpha 2 (COL1A2), hydroxyproline (HYP), PI3, AKT, mTOR, and nuclear factor erythroid 2­related factor 2 (NRF2) were assessed post-AER and SFN treatment using qPCR and western blot analysis. Results: The findings of the study revealed that AER elicited a stimulatory effect, upregulating TGFß1, COL1A2, HYP, PI3K, AKT, and mTOR and downregulating NRF2 expression. Conversely, SFN treatment significantly upregulated NRF2, inhibiting TGFß1 mediated PI3/AKT/mTOR pathway. Conclusion: These observations suggest that SFN can be used as a promising synergistic antifibrotic agent to combat fibrogenesis via the non-Smad pathway (AU)

Fibrose submucosa oral é uma desordem potencialmente maligna causada pelo habito de mascar a noz da areca, o que contribui para a dispersão de alcalóides ativos nos tecidos subepiteliais, estimulando a deposição excessiva de matriz extracelular. Há várias modalidades terapêuticas, no entanto, com eficácia limitada no controle da progressão da fibrose. O sulforafano (SFN), isotiocianato encontrado abundantemente em plantas crucíferas, é conhecido por suas propriedades antifibróticas. Objetivo: Investigar os efeitos antifibróticos do SFN na via fosfatidilinositol3-quinase (PI3K), via quinase serina/treonina 1 (AKT-1), via do alvo da rapamicina em mamíferos (mTOR), na fibrose induzida por arecolina (AER) em fibroblastos gengivais de humanos (HGFs). Material e Métodos: A meia concentração inibitória mínima de AER e SFN em 24 horas nas células HGFs foi determinada por MTT. Os níveis de expressão de ß1 (TGFß1), colágeno tipo 1 alfa 2 (COL1A2), hidroxiprolina (HYP), PI3K, AKT, mTOR, fator nuclear eritroide 2 relacionado ao fator 2 (NRF2) foram analisados após tratamento com ERA e SFN através de qPCR e western blot. Resultados: O ERA apresentou efeito estimulatório aumentando a expressão de TGFß1, COL1A2, HYP, PI3K, AKT e mTOR e diminuindo a expressão de NRF2. Por outro lado, tratamento com SFN aumentou significativamente a expressão de NRF2, inibindo a liberação de TGFß1 mediada pela via PI3/AKT/mTOR. Conclusão: Esses achados sugerem que o SFN pode ser um agente antifibrótico promissor no combate à fibrogênese decorrente da via não-Smad (AU)

Arecoline induces activation of human oral fibroblasts by promoting macrophage secretion of exosomes containing miR-155-5p / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which arecoline regulates the level of miR-155-5p in macrophage-secreted exosomes to induce the transformation of human oral mucosal fibroblasts (HOMFs) into fibroblast phenotype.@*METHODS@#Exosomes were harvested from human monocytic cell line THP-1 with or without arecoline treatment. The effects of arecoline-treated THP-1 cell culture supernatant (CS), THP-1-derived exosomes (EXO), exosome-depleted THP-1 cell supernatant (NES), miR-155-5p overexpression, and miR-155-5p inhibitor on migration ability of arecoline-treated HOMF cells were examined using Transwell migration assay. The polarization of THP-1 cells was detected using flow cytometry. DCFH-DA was used to detect the level of oxidative stress in the cells with different treatments. The mRNA and protein expressions of α- SMA, type I collagen and SOCS1 in the cells were detected with qRT-PCR and Western blotting.@*RESULTS@#Flow cytometry showed that arecoline-treated THP-1 cells exhibited obvious polarization from M0 to M1. Both the supernatant and exosomes from arecoline-treated THP-1 cells significantly enhanced the migration ability of HOMF cells, increased intracellular oxidative stress, up-regulated the expressions of miR-155- 5p and the mRNA and protein levels of α-SMA and type I collagen, and lowered the mRNA and protein expressions of SOCS1. In HOMF cells treated with exosomes from arecoline- treated THP-1 cells, overexpression of miR-155-5p significantly enhanced cell migration ability and increased cellular expressions of α-SMA and type I collagen, and miR-155-5p inhibitor caused the opposite changes.@*CONCLUSION@#Arecoline can up-regulate miR-155-5p expression in THP-1 cells and inhibit the expression of SOCS1 protein in HOMF cells via the exosome pathway, thus promoting the fibrotic phenotype transformation of HOMF cells.

Discussion and consideration on pharmacology and toxicology of Areca catechu and its rational application / 中草药

Areca catechu ranks the first of China's precious "four southern medicines", with a history of more than 1 800 years of medicinal use and extensive clinical application. The pharmacological effects of A. catechu mainly focus on insect repellent, anti-tumor, anti-aging, anti-atherosclerosis and the effects on digestive system and nervous system. In recent years, safety problems such as oral cancer caused by consumption of A. catechu have been frequently reported, and the main chemical components of both medicinal and edible A. catechu are arecoline, so the clinical safety of medicinal A. catechu has been questioned. Based on the chemical composition, this paper analyzes the pharmacological and toxicological characteristics of A. catechu, discusses the points for attention in clinical application, in order to provide a reference basis for the clinical safe and rational use of A. catechu.

Simultaneous Determination of Four Alkaloid Components in Xiangbin Decoction by UPLC-QqQ-MS/MS / 中国实验方剂学杂志

Objective: To establish a quantitative method for the simultaneous determination of arecaine,arecoline,norisoboldine and boldine in Xiangbin decoction by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-QqQ-MS/MS), and compare the variation of their contents between single and mixed decoctions. Method: The separation was carried on a Waters ACQUITY UPLC BEH Shield RP18(2.1 mm×150 mm,1.7 μm)column, with 0.1%formic acid solution-acetonitrile as mobile phase for gradient elution. The flow rate was 0.2 mL·min-1, and the column temperature was 30℃. The quantitative MRM transitions of the four components were m/z 142.10/44.11 for arecaine,m/z 156.20/44.07 for arecoline,m/z 314.29/265.12 for norisoboldine and m/z 328.13/265.10 for boldine. The determination was performed in multiple reaction monitoring (MRM) mode by mass spectrometry with electrospray ionization (ESI) source under positive mode. Result: The linear ranges of arecaine,arecoline,norisoboldine and boldine were 0.479 0-57.48,0.976 0-78.08,0.812 0-64.96, 0.091 2-18.24 μg·L-1,respectively. The average recoveries of the above compounds ranged from 93.73%to 104.34%, with RSD (n=6) of less than 5%. The contents of arecoline,arecoline,norbibeldine and boltinine in Xiangbin decoction were (90.07±1.26),(445.27±12.39),(742.35±38.39),(38.50±3.33) μg·g-1,which were significantly lower than the contents in Linderae Radix and Arecae Semen. Conclusion: The method is rapid,sensitive,accurate and reproducible,and suitable for the simultaneous determination of multiple components in Xiangbin decoction,so as to provide a basis for the quality control of Xiangbin decoction. The compatibility of Xiangbin decoction has a significant effect on the dissolution contents of arecaine,arecoline,norisoboldine and boldine.

Rat model with oral submucous fibrosis induced by arecoline and mechanical stimulation / 华西口腔医学杂志

OBJECTIVE@#The aim of this study was to induce oral submucous fibrosis (OSF) in Sprague-Dawley(SD) rat models by arecoline and mechanical stimulation.@*METHODS@#Two factors factorial design was used to divide 48 rats into 8 groups (n=6). Different concentrations of arecoline (0, 0.5, 2, and 8 mg·mL⁻¹) and mechanical stimulation (with or without brush) were treated. After 16 weeks of treatment, the mouth opening was measured, the pathological changes of the buccal mucosa were observed, and the expressions of type Ⅲ collagen, transforming growth factor β1 (TGF-β1), and interferon-γ (IFN-γ) were detected.@*RESULTS@#In rats with moderate and high concentrations of arecoline, typical OSF pathological features were observed in the buccal mucosa, the mouth openings were significantly reduced, and the expression levels of type Ⅲ colla-gen and TGF-β1 were significantly increased (P0.05).@*CONCLUSIONS@#Moderate and high concentrations of arecoline can induce OSF in SD rats, but mechanical stimulation cannot induce OSF.

Effect of arecoline on SD rat survival after buccal mucosal biopsy / 口腔疾病防治

Objective @#To provide an experimental basis for predicting the sample size needed for animal experiments by studying the survival of SD rats after buccal mucosal biopsy with arecoline administered at different concentrations with different methods.@*Methods @#In all, 48 rats were divided into 8 groups, with 6 in each group, as follows: rats in groups A-D were treated with arecoline at different concentrations (0, 0.5, 2, 8 mg/mL); rats in groups E-H were treated with arecoline at different concentrations (0, 0.5, 2, 8 mg/mL), followed by stimulation of the buccal mucosa by mechanical rubbing. After 16 weeks, a 6-mm-diameter sample of the buccal mucosa was collected, and the wound was closed with interrupted sutures. The survival time of the rats was recorded, and the relationship between the survival time and the concentration of arecoline and mechanical stimulation was analyzed. @*Results@#No rats died during the first 16 weeks after treatment or after biopsy. The success rate of the arecoline stimulation model was 66.7%. The average observation time of all SD rats after biopsy was 42.5 days. Up to 120 days after biopsy, the cumulative survival rate in the eight groups was 50%, 33%, 17%, 0%, 33%, 17%, 0% and 0%, respectively (in alphabetical order). The cumulative survival rate in the groups administered 0 mg/mL (groups A and E), 0.5 mg/mL (groups B and F), 2 mg/mL (groups C and G), and 8 mg/mL (groups D and H) was 42%, 25%, 8% and 0%, respectively. Cox survival analysis showed that moderate and high concentrations of arecoline (2, 8 mg/mL) significantly affected the survival duration (P < 0.05), while mechanical stimulation had no significant effect on the survival duration (P > 0.05). The chi-squared test showed that the survival rate of rats showing wound healing (33.3%) was significantly higher than that of rats showing incomplete wound healing (0.0%) (P=0.003). @*Conclusion @#The success rate of the rat buccal submucosal fibrosis model was higher than moderate and high concentrations of arecoline, but the survival duration was significantly reduced after biopsy. Mechanical stimulation did not lead to a significant decrease in the survival duration, and impaired wound healing may be a cause of death in this model.

Comparative study on contents of four alkaloids in homologous herbal medicines--Arecae Pericarpium and Arecae Semen / 中国中药杂志

To establish a high performance liquid chromatography (HPLC) method for simultaneous determination of four alkaloids(arecoline， guvacoline， arecaidine， and guvacine) in Arecae Pericarpium (AP) and Arecae Semen (AS), and compare the contents of these four alkaloids between different medicinal parts. The chromatographic conditions were as follows:Welch SCX（4.6 mm×250 mm， 5 μm）column, with acetonitrile-0.2% phosphoric acid solution (adjusted to pH 3.85-3.90 with ammonium hydroxide) at 50:50 as the mobile phase, at a flow rate of 0.5 mL·min⁻¹. The column temperature was set at 35 °C, and the detection wavelength was 215 nm. The results of content determination in 7 batches of AS and 10 batches of AP showed that, the contents of 4 alkaloids in AS (arecaidine 0.020%-0.045%, guvacine 0.031%-0.086%, arecoline 0.194%-0.346%, and guvacoline 0.065%-0.094%) were generally higher than those in AP (arecaidine 0.10%-0.032%, guvacine 0.006%-0.029% arecoline 0.00%-0.070%, and guvacoline 0.00%-0.020%), and most of the APs had no arecoline and arecaidine at all in fruit peel. The above results indicated that different alkaloids can be used to distinguish the different medicinal parts of Arera catechu. Arecoline， guvacoline， arecaidine， and guvacine can be used as the quality control markers of AS, while for AP, only arecaidine and guvacine were needed.

Effects of arecoline on apoptosis of human periodontal ligament fibroblasts / 口腔疾病防治

Objective @#To observe the effects of arecoline on the related protein expressions in the apoptosis of cultured human periodontal ligament fibroblasts (hPDLFs), such as p-JNK, p-p53, and Bcl-2.@*Methods @#hPDLFs were isolated from human periodontal ligament tissues and expanded in vitro. hPDLFs were treated with different concentrations of arecoline (0, 20, 40 and 80 μg/mL) for 12 h. The proliferative activities were evaluated by MTT. The expressions of p-JNK, p-p53, and Bcl-2 were determined by Western blot. @*Results@#Arecoline inhibited cell proliferation and induced apoptosis protein. The protein level of Bcl-2 was decreased, while p-JNK and p-p53 were increased (P < 0.05). The protein expressions were in a concentration-dependent manner with arecoline. @*Conclusion @#It demonstrates arecoline might contribute to the apoptosis of hPDLFs, and could destroy periodontal tissues.

Effects of arecoline and calcium ion on the permeability of dysplastic oral epithelia model in vitro / 口腔疾病防治

Objective @# To study the effects of arecolineand Calcium ion (Ca 2+) on the permeability of dysplastic oral epithelia model in vitro.@*Methods@#To establish the dysplastic oral epithelia model in vitro by culturing oral keratinocyte(DOK) and harvesting a DOK cell monolayer. The models were divided into control group, arecoline group and "Ca 2++ arecoline" group. The values of Lucifer Yellow Papp were used to estimate the permeability changes of models after treatedwith arecoline and Ca 2+. @*Results @# In arecoline group, the lucifer yellow Papp values of each subgroup were higher than that of control group (P < 0.05), and the values increased as arecoline concentration elevated and time lasted (P < 0.05). When the "Ca 2++ arecoline" group were pretreated with Ca 2+, the values of subgroup "10 μg/mL" was lower than that of the corresponding arecoline group (P > 0.05). However, the value of subgroup "4 h 10 μg/mL" of "Ca 2++ arecoline" group had no statistical difference with that of control group (P > 0.05), while the other subgroups were increased (P < 0.05); Besides, these values in "Ca 2++ arecoline" group were increased as the arecoline concentration elevated and time lasted too (P < 0.05).@*Conclusion@#Intervention of arecoline contributes to the increase of permeability of DOK cell monolayer model, which maybe an important reason for the cancerization of dysplastic oral epithelia, however Ca 2+might weaken these effects of arecoline in the process.

Effect of arecoline hydrobromide on mRNA expression of hepatic and renal transporters in vivo / 中草药

Objective: To explore the effect of arecoline hydrobromide (AH) on the expression of rat hepatic and renal transporters. Methods: The effect of AH on the mRNA expression of 13 hepatic and renal transporters was studied after orally giver AH (0.8, 4, and 20 mg/kg/d) to rats for 21 d. Results: The results from the real-time PCR indicated that, AH treatment at low dose significantly decreased the mRNA levels of hepatic MRP2 and MDR1A, while significantly increased renal MRP5 mRNA level. On the other hand, AH treatment at high dose significantly inhibited the mRNA expression of hepatic OCT2, OAT2, OCTN2, OATP1A1, OATP1A4, OATP2B1, MRP2, and MDR1A, as well as renal MRP2, BCRP, and MDR1A. However, the mRNA expression of renal OCTN2, OATP1A1, OATP1A4, and MRP5 were significantly up-regulated following the treatment of high dose of AH. And the AH-induced effect on the above transporters was dose dependent in some extent. Conclusion: Due to the drug interaction caused by the alteration in expression and function of hepatic and renal transporters, it is suggested that the betel nut addicts should be paid more attention in case of adverse drug interactions.

Development of a mouse model of arecoline-induced oral mucosal fibrosis

Objective To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes. Methods BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type I and collagen type III, and angiogenesis were measured. Results In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type I changed significantly as the diseases advanced (P < 0.05); however, collagen type III was not statistically different. Conclusions An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type I.

Development of a mouse model of arecoline-induced oral mucosal fibrosis

OBJECTIVE@#To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.@*METHODS@#BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type I and collagen type III, and angiogenesis were measured.@*RESULTS@#In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type I changed significantly as the diseases advanced (P < 0.05); however, collagen type III was not statistically different.@*CONCLUSIONS@#An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type I.

In vivo effect of arecoline hydrobromide on rat hepatic CYP2B expression and its mechanism / 中草药

Objective: To study the effect of arecoline hydrobromide (AH) on rat hepatic CYP2B expression/activity, as well as the underlying regulation mechanism in vivo. Methods: After oral administration of AH (4, 20, and 100 mg/kg/d) to rats for 7 consecutive days, the hepatic CYP2B activity was detected by LC-MS/MS method, the protein levels of hepatic CYP2B, total CAR, and endonuclear CAR were detected by Western blotting, and the hepatic CYP2B1 mRNA level was detected by real-time PCR. Results: AH treatment had no effect on rat hepatic CYP2B protein level, but the hepatic CYP2B1 mRNA level was dose-dependently increased. Additionally, although the hepatic CYP2B activity was induced by AH treatment, the induction was weakened with the dose increase of AH. Furthermore, the protein content of hepatic endonuclear CAR was increased while the total CAR protein remained unchanged following AH treatment. Conclusion: AH induces rat hepatic CYP2B by promoting nuclear translocation of CAR. The regulation of AH on rat hepatic CYP2B largely involve transcriptional activation of the gene, partially involve the post-translational modification of CYP2B protein. Our results also suggest that the risk of metabolic interaction could be existed when the substrate drugs of CYP2B are administered in betel-quid used human.

Induction of rat hepatic CYP2E1 expression by arecoline in vivo / 药学学报

The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg·kg-1·d-1) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepatic CYP2El does not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- translational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human.

Constituents Released from Streptococcus mutans Attenuate Arecoline-mediated Cytotoxicity in HGF Cells by Altering Intracellular Ca2+ Signaling

Streptococcus mutans (S. mutans) is a facultative anaerobic bacterium mainly found in the oral cavity and is known to contribute to tooth decay and gingivitis. Recent studies on intestinal microbiota have revealed that microorganisms forming a biofilm play important roles in maintaining tissue homeostasis through their own metabolism. However, the physiological roles of oral microorganisms such as S. mutans are still unclear. In our current study, we identified that constituents released from S. mutans (CR) reduce arecoline-mediated cytotoxicity without producing toxic effects themselves. Arecoline, as a major alkaloid of areca nut, is known to mediate cytotoxicity on oral epithelial cells and induces a sustained intracellular Ca2+ ([Ca2+]i) increase that is cytotoxic. The exposure of human gingival fibroblast (HGF) cells to CR not only inhibited the sustained [Ca2+]i increase but also the initial [Ca2+]i elevation. In contrast, CR had no effects on the gene regulation mediated by arecoline. These results demonstrate that S. mutans has physiological role in reducing cytotoxicity in HGF cells and may be considered a novel pharmaceutical candidate.

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

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.

HPLC determination of arecoline in Arecae Pericarpium from different habitats / 中国药学杂志

OBJECTIVE: To establish a quantitative determination method for arecoline in Arecae Pericarpium. METHODS: The determination was performed on thermo-biobasic SCX column (4.6 mm×250 mm, 5 μm) with mobile phase consisting of acetonitrile-phosphoric acid solution (55;45). The flow rate was 1.0 mL·min-1, the column temperature was 30°C, and the detection wavelength was 215 nm. RESULTS: The method had good linear relationship for arecoline hydrobromide in the range of 5.2-83.2 μg·mL-1 (r=0.9991). The average recovery (n=9) was 98.8% for arecoline hydrobromide. CONCLUSION: The method is simple, accurate and specific. It provides a reliable way for evaluating the quality of Arecae Pericarpium.

Efectos bucales de la nuez de betel / Oral effects of the betel nut

La nuez de betel o nuez de areca es una semilla de la palmetra de betel (areca catechu), una de las plantas más polulares del mundo. Diversos pueblos asiáticos, por influencias culturales, tienen la costumbre de masticar la semilla de esta especie vegetal. Entre sus principios activos, la arecaina y la arecolina, son alcaloides comparables a la nicotina en los efectos nerviosos estimulantes. La sustancia activadora causa un relajamiento agradable en la boca, sensación que se propaga al sistema nervioso central. Sin embargo, masticar regularmente la nuez de betel, tiñe la saliva de rojo vivo y ennegrece los dientes, siendo extremadamente perjudicial para la salud oral, causando la pérdida precoz de dientes. A pesar de sus efectos maléficos, existe la dificultad de erradicar el hábito, debido a su carácter cultural, donde las manchas son motivo de orgullo. La agencia internacional de investigación del cáncer (IARC) clasifica a la nuez de betel como un cancerígeno, existiendo numerosos estudios que relacionen la costumbre con neoplasias bucales. El estudio tiene por finalidad realizar un análisis crítico sobre el uso de esta sustancia, buscando informar a la comunidad para prevenir sus efectos maléficos.

The betel nut or areca nut is the seed of the palm tree of bétele (areca catechu), one of the most popular plants of the world. Asians, by cultural influence, have the custom of chew the seed of this sort of vegetable. Between its active principles: arecaine and arecoline, they are alkaloids comparable to the nicotine in the neural stimulation effects. The active substance causes a pleasant relaxion sensation in the mouth, sensation that is extended to the central nervous system. However, chewing regularly betel nut dryes of red the saliva and blackens the teeth being extremely harmful to the mouth health causing early the loss of the teeth. Despite of the harmful effects, the difficulty to eliminate this habit is due to its deep cultural character. Chewing bétel nuts and have the teeth stained it's a motive of proud. The International Agency of Research of the Cancer (IARC) classifies the bétel nut as carcinogenic acquaintance, and the literature have many studies that relate this custom with the oral cancer. The study has as goal to do a critical analysis of the utilization of this substance, searching to inform to the community their bad effects.

Oral submucous fibrosis : current concepts in etiopathogenesis.

Oral submucous fibrosis (OSF) is now accepted globally as an Indian disease, having highest malignant potential than any other oral premalignant lesions. The understanding of the exact role of alkaloids and other etiological agents with respect to pathogenesis will help the management and minimize the blind clinical trials and treatment modalities. This article provides an overview of the etiopathogenesis with stress on the recent concepts related to this chronic “Indian Disease”.

Effects of Jian-Xing on three animal models to mimic muscle tremors of Parkinson's disease / 中国康复理论与实践

@#ObjectiveTo develop three animal models to mimic muscle tremors of Parkinson's disease and observe effects of Chinese herb compounds Jian-Xing on these models.MethodsPure muscle tremor mice models were developed by single intraperitoneal injection of arecoline or oxotremorine. The mitochondria damaged model was developed by intraperitoneal injection of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) 20mg/kg for 8 days. Duration time of tremoring was recorded. The climbing time and spontaneous movements of MPTP mice were recorded. HPLC was used to detect the content of dopamine and it's metabolites in MPTP mice.ResultsAfter injection of oxotremorine or arecoline,model mice exhibited significant tremoring, duration time of tremor of mice in Jian-Xing group shortened significantly. As to MPTP model mice, climbing time of model mice prolonged, times of spontaneous movements of model mice decreased and the content of dopamine in striaturn decreased compared with control group. Climbing time of mice in Jian-Xing group shortened, spontaneous movements increased and content of dopamine increased distinctively. ConclusionOxotremorine, arecoline and MPTP all can produce tremor animal models. Chinese herb compounds Jian-Xing can shorten the duration time of tremor.As to MPTP model, Jian-Xing can shorten the climbing time of model mice, increase the spontaneous movements and increase the content of dopamine in striaturn.