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 highdose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type Ⅰ.

Analysis of arecoline in Semen Arecae decoction pieces by microchip capillary electrophoresis with contactless conductivity detection

A new method for the determination of arecoline in Semen Arecae decoction pieces by microchip capillary electrophoresis with contactless conductivity detection （MCE-CCD） was proposed. The effects of various electrophoretic operating parameters on the analysis of arecoline were studied. Under the optimal conditions, arecoline was rapidly separated and detected in 1 rain with good linearity over the concentration range of 20 1500 uM （r2=0.9991） and the detection limit of 5 uM （S/N=3）. The method was used for the analysis of arecoline satisfactorily with a recovery of 96.8 -104%.

Synthesis and Their Endothelium Vascular Relaxation of Arecoline Derivatives Containing Oxadiazoline

Ten novel 1, 1-dimethyl-3-(2-or 5-aryl-4-acetyl-2, 3-dihydro-1, 3, 4-oxadiazoline-5-or- 2-yl)-1, 2, 5, 6- tetrahydropyridinium iodides were synthesized from starting material nicotinalde- hyde or nicotinic acid by two different synthetic methods respectively. The preliminary bioactive tests indicate som compounds exhibit potent relaxing effect on endothelial cells, comparable to Ach or arecoline.

Effects of Arecoline on Calcium Channel Currents and Caffeine-induced Calcium Release in Isolated Single Ventricular

The effects of Arecoline (Are) on calcium m obilization were investigated. In isolated single ventricular m yocyte of guinea pig,patch clamp whole cell recording techniques were used to record the current of L - type calcium channel and cytosolic Ca2 + level ([Ca2 + ]i) labeled with fluo- rescence probe Fluo- 3/ AM was m easured under a laser scanning confocal microscope.Results re- vealed that Are(3- 10 0 μm ol/ L) could inhibit L- type calcium current in a concentration- depen- dent manner and the value of IC50 was33.73μm ol/ L (n=5 ) .In the absence of extracellular calci- um,the resting levels of[Ca2 + ]i was not affected by Are(n=6 ,P>0 .0 5 ) ,but pretreatment with Are(30 μmol/ L) could significantly inhibit the[Ca2 + ]i elevation induced by caffeine(10 m mol/ L,n=6 ,P<0 .0 1) .It was concluded that Are could inhibit not only calcium influx through L- type calcium channel but also calcium release from sarcoplasm ic reticulum.

Security of a Novel Antitapeworm Drug:Arecoline Hydrobromide

[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Method] The security of arecoline hydrobromide was evaluated based on acute toxicity tests; the ranges of safe medication, tolerability and toxicity as well as ＂Three-induced＇ effects （carcinogensis, mutagene- sis and teratogenesis） and reproductive toxicity were summarized according to the combinations of experimental results, papers and clinical effects. E Result] The results of acute toxicity tests in mice and rats showed that LD^0 （50% lethal dosages） of arecoline hydrobromide in mice was 691.83 mg/（kg.BW） and 95% incredible range of its LDso was 642.92 -744.47 mg/（ kg. BW）, and LDso of arecoline hydrobromide in rats was 2 054 mg/（kg.BW） and 95% incredible range of its LDso was 1 908 -2 210 mg/（kg.BW）. Its LDso value was hundreds times higher than the recommen- ded clinical dosage [ 1 -5 mg/（kg-BW） ], therefore it is safe to apply in clinic. The research results of ranges of safe medication, tolerability and toxicity showed that arecoline hydrobromide could entirely dispel the dog Diphyllobothrium, Spirometra mansoni, Dipylidium mesocestoides, Linea- tus and Cysticercus at dosages of 2 -3 mg/（ kg.BW）, and the same effects to Railletina tapeworm of chickens and Drepanidotaenia lanceolata of duck and goose at dosages of I -2 mg/（kg.BW）. The arecoline hydrobromide had muscarinic effects as side-effects and could cause vomiting, di- arrhea and other clinical symptoms to discharge the paralyzed worm from livestock body rapidly and completely. The arecoline hydrobromide had ＂Three-induced＂ effects and reproductive toxicity when it was used as antitapeworm drug with long-term, sustained and a large number of drug us- age, rather than used in clinical application with shorter time and lower dosage of administration. [ Conclusion] The arecoline hydrobromide is low- toxic substance and has a certain of toxicity such as ＂Three-induced＂ effects and reproductive toxicity at high-dosages application, and there are good effects on livestock and poultry tapeworm at the clinical recommended dosacles without ＂Three-induced＂ effects and reproductive toxicity.

Effects of Arecoline Hydrobromide on Taeniasis and Cysticercosis in Domestic Animals

Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bodies because they can attack many organs of body. According to the combination of experimental results and literature materials, the morphology and transmission mode of taenia and cysticercus, the prevalence status and monitoring of taeniasis and cysticercosis as well as the antitapeworm mechanism, comparative analysis to other drugs, expelling tapeworm tests in vitro, dose determining tests and usage notes of arecoline hydrobromide were expounded in detail. It provides a theoretical basis for prevention of taeniasis and cysticarcosis and more scientific usage of arecoline hydrobromide and thus relieves the harms of taeniasis and cysticercosis and ensuring the public health security.

Research Progress in Arecoline-induced Oral Submucous Fibrosis

Areca nut is a popular fruit, but is among the most common addictions following tobacco, alcohol and caffeine globally. Areca nut chewing is the major risk factor for OSF, which is a chronic, occult, and premalignant fibrotic disease. OSF is characterized by submucosal collagen accumulation and microvascular diseases, the primary microscopic manifestations of which include damaged vascular endothelial cells, increased vascular permeability, and decreased number of microvessels. As the basic structure of microvessels, endothelial cells paly an important role in the pathogenesis and progression of OSF. Arecoline is the main component of areca nut. This review summarized the machenism of arecoline-inducing OSF by acting on endothelial cells, mainly including that arecoline can promote endothelial cells inducing tissue fibrosis by acting on the vascular endothelial cells and is accomplished via multiple aspects such as inhibiting the proliferation and facilitating the apoptosis of endothelial cells, affecting their secretion of cytokines, or promoting the transformation process of EMT.

An emerging role of arecoline on growth performance,intestinal digestion and absorption capacities and intestinal structural integrity of adult grass carp(Ctenopharyngodon idella)

Arecoline is an alkaloid with important pharmacological effects in the plant areca nut,which has been demonstrated to be an agonist of muscarinic receptors(M receptor).This study explored the influences of dietary arecoline on growth performance,intestinal digestion and absorption abilities,antioxidant capacity,and the apical junction complex(AJC)of adult grass carp(Ctenopharyngodon idella).Adult grass carp(608to 1512 g)were fed at 6 graded levels of dietary arecoline(0,0.5,1.0,1.5,2.0,and 2.5 mg/kg diet)for 9weeks.The results suggested that appropriate dietary supplementation of arecoline(1.0 mg/kg)increased growth parameters and intestinal growth in adult grass carp(P<0.05),enhanced digestion and absorption capacities(P<0.05),up-regulated muscarinic receptor 3(M3)mRNA level(P<0.05),increased the content of neuropeptide fish substance P(P<0.05),improved antioxidant capacity by activating the Keap1a/Nrf2signaling pathway(P<0.05),reduced intestinal mucosal permeability(P<0.05),and increased m RNA levels of tight junction(TJ)and adherent junction AJ-related proteins in fish by inhibiting the RhoA/ROCK signaling pathway(RhoA/ROCK/MLCK/NMII)(P<0.05).In addition,the appropriate arecoline supplementation for adult grass carp was determined to be 1.20,1.21,1.07,and 1.19 mg/kg based on percentage weight gain,lipase activity,serum diamine oxidase,and protein carbonyl,respectively.Overall,to the best of our knowledge,we investigated for the first time the effects and possible mechanisms of dietary arecoline on intestinal digestive and absorptive capacities and structural integrity in fish and evaluated the appropriate level of supplementation.

Frequency- and state-dependent blockade of human ether-a-go-go-related gene K^＋ channel by arecoline hydrobromide

Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.

银杏外种皮对钉螺的杀灭机理

To study the toxicity of extracts of Ginkgo biloba sarcotesta to Oncomelania hupensis,snails were exposed to 40% and 80% of 24 h LC 50 of the extract of Ginkgo bilba for 24 h,choline esterase(ChE),alanine aminotransferase(ALT),alkaline phosphatase(ALP),lactate dehydrogenase(LDH),succino dehydrogenase(SDH),malic dehydrogenase(MDH)activities in cephalopodium and liver were determined by enzyme kinetic assay.Arecoline and niclosamide were used as reference molluscicides.The results showed that sarcotesta of Ginkgo biloba could inhibit ChE,ALT,ALP and MDH activities both in cephalopodium and liver;arecoline could inhibit ChE,ALP,SDH and MDH activities in cephalopodium and ChE,ALT,ALP,SDH and MDH activities in liver.Niclosamide had inhibitory effects upon ChE,ALT,ALP,SDH and MDH activities in cephalopodium,and ChE,ALT,ALP and SDH activities in liver.All three molluscicides did not inhibite LDH activity in cephalopodium and liver.These results indicate that lethal effects of extracts of sarcotesta of Ginkgo biloba are mediated via inhibition of MDH activitiy,and interference with the NADH respiratory chains.Inhibition of vital enzymic mechanisms causes snails to death.