In Silico profiling of the Angiotensin converting enzyme binding affinities, toxicity and Pharmacokinetics of compounds from the nuts of Areca Catechu, Linn. and its bioisosteres

Background@#Hypertension is a worldwide epidemic that has been recognized as the most leading global risk for mortality, with its prevalence associated with increased blood pressure, concomitant risks of cardiovascular and kidney diseases, and major commonality in individuals advanced in age. With the current treatment options for hypertension management, there is still a need to develop therapies that directly target receptors that aid in hypertension treatment.@*Methodology@#The study focused on the in-silico profiling of the reported compounds from Areca catechu L. (fam. Arecaceae) towards the n-domain and c-domain angiotensin converting enzyme (ACE) receptor models. Bioisosteric replacement was used to create bioisosteres investigated for similar binding affinity.@*Results@#Some A. catechu compounds exhibited favorable binding energies towards the n- and c-domain receptor models of ACE, binding in the same ACE ligand binding site as lisinopril, benazepril, and sampatrilat via similar interactions and amino acid residues. The majority of A. catechu compounds with favorable ACE binding energies belong to the phytochemical classes of flavonoids, polyphenols and phenolics, glycosides, and steroids. After in silico toxicity and pharmacokinetic profiling, the bioisosteres Leuco-DM02-39, Leuco-DM02-66, Leuco-DM05-60, Querc-DM09-63, and Querc-DM14-31 with binding energies higher than their parent compounds and comparable to lisinopril, benazepril, and sampatrilat were deemed the best.@*Conclusion@#A. catechu compounds have the potential to target ACE n-domain and c-domain receptor models. Three leucocyanidin and two quercetin bioisosteres exhibited favorable binding to the n-domain and c-domain ACE receptor models and could be further optimized to derive a promising antihypertensive agent through ACE inhibition.

Water migration and kinetics of Arecae Semen during moistening process / 中国中药杂志

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.

Anti-hypoxic pharmacological effects of betelnut polyphenols / 中南大学学报(医学版)

Areca catechu L. medicinal materials and their preparations are widely used in clinical practice. Betelnut polyphenol is one of the main chemical components with antioxidant, anti-inflammatory, and antibacterial effects. With continuous increase of high altitude activities, tissue oxidative damage caused by high altitude hypoxia seriously affects the ability to work, and the studies on anti-hypoxia drugs are particularly important. Recent studies have shown that betelnut polyphenols have protective effects on oxidative stress injury caused by hypoxia via improving blood gas index of hypoxic organism, increasing superoxide dismutase glutathione catalase activity, and scavenging excessive free radicals. The effects of betelnut polyphenols against hypoxia and oxidative damage protection suggest that betelnut polyphenols can be used as potential anti-hypoxia drugs and posses clinical prospects.

Investigation of anti-Alzheimer's activity of aqueous extract of areca nuts (Areca catechu L): in vitro and in vivo studies / Investigación de la actividad anti-Alzheimer del extracto acuoso de nueces de areca (Areca catechu L): estudios in vitro e in vivo

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Sever cognitive and memory impairments, huge increase in the prevalence of the disease, and lacking definite cure have absorbed worldwide efforts to develop therapeutic approaches. Since many drugs have failed in the clinical trials due to multifactorial nature of AD, symptomatic treatments are still in the center attention and now, nootropic medicinal plants have been found as versatile ameliorators to reverse memory disorders. In this work, anti-Alzheimer's activity of aqueous extract of areca nuts (Areca catechu L.) was investigated via in vitro and in vivo studies. It depicted good amyloid ß (Aß) aggregation inhibitory activity, 82% at 100 µg/mL. In addition, it inhibited beta-secretase 1 (BACE1) with IC50 value of 19.03 µg/mL. Evaluation of neuroprotectivity of the aqueous extract of the plant against H2O2-induced cell death in PC12 neurons revealed 84.5% protection at 1 µg/mL. It should be noted that according to our results obtained from Morris Water Maze (MWM) test, the extract reversed scopolamine-induced memory deficit in rats at concentrations of 1.5 and 3 mg/kg.

La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo relacionado con la edad. Los severos deterioros cognitivos y de la memoria, el enorme aumento de la prevalencia de la enfermedad y la falta de una cura definitiva han absorbido los esfuerzos mundiales para desarrollar enfoques terapéuticos. Dado que muchos fármacos han fallado en los ensayos clínicos debido a la naturaleza multifactorial de la EA, los tratamientos sintomáticos siguen siendo el centro de atención y ahora, las plantas medicinales nootrópicas se han encontrado como mejoradores versátiles para revertir los trastornos de la memoria. En este trabajo, se investigó la actividad anti-Alzheimer del extracto acuoso de nueces de areca (Areca catechu L.) mediante estudios in vitro e in vivo. Representaba una buena actividad inhibidora de la agregación de amiloide ß (Aß), 82% a 100 µg/mL. Además, inhibió la beta-secretasa 1 (BACE1) con un valor de CI50 de 19,03 µg/mL. La evaluación de la neuroprotección del extracto acuoso de la planta contra la muerte celular inducida por H2O2 en neuronas PC12 reveló una protección del 84,5% a 1 µg/mL. Cabe señalar que, de acuerdo con nuestros resultados obtenidos de la prueba Morris Water Maze (MWM), el extracto revirtió el déficit de memoria inducido por escopolamina en ratas a concentraciones de 1,5 y 3 mg/kg.

Domestic and international research progress of edible and medicinal Arecae Semen / 中国中药杂志

Arecae Semen, as the first place among "Four South Medicines" in China, has great dual-use value of medicine and food. The research of Arecae Semen was mainly focused on the active ingredients and efficacy value, and its potential safety hazards were also concerned. Until now, there is still a lack of clear boundaries between medicine and food, resulting in its safety cannot be guaranteed. Therefore, it is of great significance to establish clear boundaries of medicine and food use and health risk assessment. In this paper, the differences of pretreatment and application methods of Arecae Semen were analyzed, and the research progress of Arecae Semen in chemical composition identification and toxicology research and safety evaluation were reviewed emphatically. Finally, the differences of quality control and safety evaluation of Arecae Semen in pharmacopoeias or standards were analyzed at home and abroad. It was expected to provide reference value for quality control, safety evaluation and international standardization research of Arecae Semen.

Comparative anthelmintic efficacy of Arundo donax, Areca catechu, and Ferula assa-foetida against Haemonchus contortus / Eficácia anthelmíntica comparativa de Arundo donax, Areca catechu e Ferula assa-foetida contra Haemonchus contortus

Abstract In the present study, anthelmintic activities of Arundo (A.) donax L., Areca (Ar.) catechu L., and Ferula (F.) assa-foetida L. were determined. Leaves of A. donax L., latex of F. assa-foetida L. and seeds of Ar. catechu L. in different solvent fractions were subjected to in vitro (egg hatch assay; EHA, and adult motility assay; AMA) and in vivo (faecal egg count reduction test; FECRT) tests of anthelmintic activity using Haemonchus contortus model. In the AMA, crude aqueous methanol extracts (CAME) and ethyl acetate fractions of F. assa-foetida at 10 hr post-treatment showed maximum mortality of H. contortus at 12.5-50 mg mL-1. In the EHA, CAME of F. assa-foetida was identified as a potent ovicide based on its low LC50 (16.9 µg mL-1), followed in order by Ar. catechu and A. donax. Results from the FECRT also showed the extract of F. assa-foetida L. to be more effective than those of Ar. catechu L. and A. donax L., against the gastrointestinal parasitic nematodes. Chloroform and ethyl acetate fractions showed better anthelmintic activities against the adult worms in vitro, while CAME of these plants were better than their crude powders in vivo. It is recommended to document and investigate indigenous knowledge of possible medicinal plants to plan scientific trials that may justify their endorsement.

Resumo No presente estudo, as atividades anti-helmínticas de Arundo (A.) donax L., Areca (Ar.) Catechu L. e Ferula (F.) assa-foetida L. foram determinadas. Folhas de A. donax L., látex de F. assa-foetida L. e sementes de Ar. catechu L. em diferentes frações de solvente foram submetidos a testes in vitro (teste de eclosão de ovos, EHA e ensaio de motilidade em adultos, AMA); e in vivo (teste de redução da contagem de ovos fecais, FECRT) de atividade anti-helmíntica, usando-se Haemonchus contortus. Na AMA, extratos aquosos brutos de metanol (CAME) e frações de acetato de etila de F. assa-foetida. Dez horas pós-tratamento, apresentaram mortalidade máxima de H. contortus em 12,5-50 mg mL-1. No EHA, CAME de F. assa-foetida foi identificado como um ovicida potente baseado em seu baixo LC50 (16,9 µg mL-1), seguido em ordem por Ar. catechu e A. donax. Os resultados do FECRT também mostraram que o extrato de F. assa-foetida L. é mais eficaz do que o de Ar. catechu L. e A. donax L., contra nematoides parasitas gastrointestinais. As frações clorofórmio e acetato de etila mostraram melhores atividades anti-helmínticas contra vermes adultos in vitro, enquanto o CAME dessas plantas foi melhor do que o pó bruto in vivo. Recomenda-se documentar e investigar o conhecimento indígena de possíveis plantas medicinais para planejar ensaios científicos que possam justificar seu endosso.

Effect of Acacia catechu and alum hot sitzbath on post-operative pain in patients treated with herbal seton / Efeito do banho quente de assento com Acacia catechu e alume na dor pós-operatória em pacientes tratados com seton à base de plantas

ABSTRACT Background Post-operative pain is the major consequence of Ksarasutra, Seton technique employed in Ayurvedic management of Low anal fistula. Surgeons are forced to prescribe Opioids and NSAIDs with pronounced untoward effects. Non pharmacological measures like Balneotherapy are used to improve circulation and relieve spasm in contemporary sciences. Aim To compare the efficacy of Khadira (Acacia catechu) and Sphatika (Potash alum) hot sitzbath with plain hot sitzbath in patients of low anal fistula treated with Ksarasutra. Method The study was single blind, double armed; prospective, randomized control clinical trial in which 30 patients were randomly allocated into two groups of 15 each on the basis of inclusion and exclusion criteria. Group A received hot sitzbath using Acacia catechu and alum infusion twice daily for 21 days. Group B received hot sitzbath using warm water for 21 days. The assessments were made on pain, post-surgical satisfaction burning sensation, tenderness, discharge, constipation, itching and incontinence. Result The disease was prevalent in the 4th decade of life, more in males (86.67%) involved in sedentary work (53.33%) residing in urban domicile, consuming mixed diet (100%). Both groups showed statistically significant improvement in outcome measures like pain, burning sensation, tenderness, discharge, constipation and itching. Conclusion On comparative analysis Acacia and Alum hot sitzbath was more effective in outcomes like pain, surgical satisfaction, burning sensation and discharge. There was no difference in the effect of both interventions with respect to outcome measures like constipation, itching and incontinence.

RESUMO Justificativa A dor pós-operatória é a principal consequência da técnica que utiliza seton de Ksarasutra no tratamento ayurvédico de fístula anal baixa. Os cirurgiões são impelidos a prescrever opiáceos e AINEs que possuem efeitos indesejáveis pronunciados. Medidas não farmacológicas como a balneoterapia são usadas nas ciências contemporâneas para melhorar a circulação e aliviar o espasmo. Objetivo Comparar a eficácia do banho quente de assento com Khadira (Acacia catechu) e Sphatika (Potash alum) com apenas banho de assento em pacientes com fístula anal baixa tratados com Ksarasutra. Método Estudo clínico prospectivo, cego e controlado de dois braços randomizados, no qual 30 pacientes foram alocados aleatoriamente em dois grupos de 15 pacientes cada com base nos critérios de inclusão e exclusão. O Grupo A recebeu banho de assento com Acacia catechu e infusão de alume duas vezes ao dia por 21 dias. O Grupo B recebeu banho de assento com água morna por 21 dias. Os desfechos avaliados foram dor, satisfação pós-cirúrgica, sensação de queimação, sensibilidade, corrimento, constipação, prurido e incontinência. Resultado A doença foi prevalente na 4ª década de vida, mais frequente no sexo masculino (86,67%), nos envolvidos em trabalho sedentário (53,33%), nos residentes em domicílios urbanos e nos que consumiam dieta mista (100%). Ambos os grupos apresentaram melhora estatisticamente significativa na avaliação dos resultados, tais como dor, sensação de queimação, sensibilidade, corrimento, constipação e prurido. Conclusão Na análise comparativa, o banho quente de assento com acácia e alume foi mais eficaz nos desfechos de dor, satisfação cirúrgica, sensação de queimação e corrimento. Não houve diferença em relação ao efeito de ambas as intervenções sobre os desfechos de constipação, prurido e incontinência.

Relationship among areca nut, intracellular reactive oxygen species, and autophagy / 华西口腔医学杂志

The relationship between areca nut as a primary carcinogen and oral cancer has been widely concerned. Areca can change the levels of reactive oxygen species (ROS) and autophagy in cells, and the levels of ROS and autophagy are closely related to the occurrence and development of tumors. This paper reviewed the relationships among areca nut, intracellular ROS, and autophagy.

wareness and knowledge of oral cancer among 1 483 residents in Beijing / 北京大学学报(医学版)

OBJECTIVE@#To investigate the oral cancer awareness, its related knowledge among residents in Beijing.@*METHODS@#A questionnaire survey was conducted among Beijing residents (non-medical related personnel) on the knowledge of oral cancer and its prevention and treatment.@*RESULTS@#A total of 1 483 questionnaires were completed, including 663 males (44.6%) and 820 females (55.3%), ranging from 15 to 91 years. Lung cancer was the most mentioned as heard of (94.3%), followed by liver cancer (92.5%) and gastric cancer (92.4%), while oral cancer was the least heard of (47.7%). Family account (P=0.015), residence (P=0.028), income (P=0.024), frequency of brushing teeth (P<0.001), frequency of mouth self-examination (P<0.001) and chew betel nut chewing (P=0.015) were significantly associated with oral cancer awareness. Most respondents learned about oral cancer from TV programs (24.3%), phone news (22.0%), WeChat (11.3%) and chatting with friends or people around (14.6%). Only 34.9% knew that smoking was a risk factor of oral cancer, and this knowledge was associated with age (P=0.011), education level (P=0.007), frequency of brushing teeth (P<0.001), and frequency of mouth self-examination (P=0.002). Only 23.5% knew that drinking was a risk factor of oral cancer, and this knowledge was associated with education level (P=0.002), residence (P=0.022), frequency of brushing teeth (P=0.009), and frequency of mouth self-examination (P=0.005). Only 35.1% knew that betel nut chewing was a risk factor for oral cancer, and this knowledge was associated with age (P=0.040), education level (P=0.002), family account (P=0.002), income (P=0.005), frequency of brushing teeth (P=0.001), frequency of mouth self-examination (P<0.001), and betel nut chewing (P=0.002). Only 35.7%, 21.6% and 16.9%, respectively, knew that long-term unhealed ulcers, white plaques and red plaques in the mouth were the early signs of oral cancer.@*CONCLUSION@#This survey demonstrates a general lack of public awareness and knowledge about signs and symptoms of oral cancer, and its risk factors and treatment. Some residents have not formed good oral hygiene habits. Specific measures should be taken to improve the public awareness of oral cancer and related knowledge about prevention and treatment, such as the use of various new media for the public to promote their oral health knowledge, in order to reduce the incidence of oral cancer, improve early attendance rates and the patients' survival rates.

Anatomical and histochemical comparison of the primary and adventitious roots of Attalea microcarpa (Arecaceae) at the initial growth stage

We describe the anatomical structure of roots originating from the apocole of Attalea microcarpa compared to the primary root, by means of usual methods for optical microscopy. The adventitious roots are differentiated in the apocole associated to vascular bundles, and can remain as a single structure or branch. They have the basic root structure characteristic of Arecoideae palms, without schizogenous spaces, which are observed in the primary root, in addition to few air spaces. Mucilages, starch and proteins were present in both types of roots. Adventitious roots of the apocole are described for the first time in Arecaceae. (AU)

Correlation of Betel Quid with Oral Cancer from 1998 to 2017: A Study Based on Bibliometric Analysis / 中华医学杂志(英文版)

Background@#Betel quid chewing has been a major risk factor for oral cancer (OC) in southern China. This study aimed to analyze the scientific publications on the relationship between betel quid chewing and OC and construct a model to quantitatively and qualitatively evaluate pertinent publications from 1998 to 2017.@*Methods@#The publications from 1998 to 2017 were retrieved from the Web of Science Core Collection database. Microsoft Excel, Thomson Data Analyzer, VOSviewer, and CiteSpace software were used to analyze the publication outcomes, journals, countries/regions, institutions, authors, research areas, and research frontiers.@*Results@#A total of 788 publications on the relationship between betel quid chewing and OC published until October 25, 2017, were identified. The top 4 related journals were Journal of Oral Pathology Medicine, Oral Oncology, Plos One, and International Journal of Cancer. The top five countries engaged in related research included China, India, the United States, the United Kingdom, and Malaysia. The corresponding disciplines, such as oncology, oral surgery, pathology, environmental and occupational health, and toxicology, were mainly concentrated in three disciplines. The subject terms squamous cell carcinoma, OC, betel quid, expression, oral submucous fibrosis, India, and p53 ranked first among research hotspots. The burst terms squamous cell carcinoma, OC, betel quid, and expression ranked first in research frontiers.@*Conclusions@#Research in this area emphasized hotspots such as squamous cell carcinoma, OC, oral submucosal fibrosis, betel quid, and tobacco. The annual number of publications steadily decreased from 1998 to 2017, with a lack of a systematic study from interdisciplinary perspectives, inadequate pertinent journals, limited regions with the practice of betel quid chewing, and insufficient participation of researchers, which indicate that as the prevalence of OC increases, particularly in China, research in this area warrants further expansion.

Areca Nut Chewing and the Risk of Re-hospitalization and Mortality Among Patients With Acute Coronary Syndrome in Pakistan / 예방의학회지

OBJECTIVES: Areca nut is widely consumed in many parts of the world, especially in South and Southeast Asia, where cardiovascular disease (CVD) is also a huge burden. Among the forms of CVD, acute coronary syndrome (ACS) is a major cause of mortality and morbidity. Research has shown areca nut chewing to be associated with diabetes, hypertension, oropharyngeal and esophageal cancers, and CVD, but little is known about mortality and re-hospitalization secondary to ACS among areca nut users and non-users. METHODS: A prospective cohort was studied to quantify the effect of areca nut chewing on patients with newly diagnosed ACS by categorizing the study population into exposed and non-exposed groups according to baseline chewing status. Cox proportional hazards models were used to examine the associations of areca nut chewing with the risk of re-hospitalization and 30-day mortality secondary to ACS. RESULTS: Of the 384 ACS patients, 49.5% (n=190) were areca users. During 1-month of follow-up, 20.3% (n=78) deaths and 25.1% (n=96) re-hospitalizations occurred. A higher risk of re-hospitalization was found (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.29 to 3.27; p=0.002) in areca users than in non-users. Moreover, patients with severe disease were at a significantly higher risk of 30-day mortality (aHR, 2.77; 95% CI, 1.67 to 4.59; p < 0.001) and re-hospitalization (aHR, 2.72; 95% CI, 1.73 to 4.26; p < 0.001). CONCLUSIONS: The 30-day re-hospitalization rate among ACS patients was found to be significantly higher in areca users and individuals with severe disease. These findings suggest that screening for a history of areca nut chewing may help to identify patients at a high risk for re-hospitalization due to secondary events.

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer / 한국역학회지

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer / 한국역학회지

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.

Epidemiological investigation of chewing fresh or dried betel nut and oral mucosal disease / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study was conducted to investigate the effect of chewing fresh or dried betel nut on the inci-dence and canceration of oral mucosa disease in Haikou City in Hainan Province.</p><p><b>METHODS</b>Through a survey questionnaire, clinical examination, and regular follow-up, we collected clinical data from 1 722 cases and divided them into two groups, among which 704 of the afflicted people chew dried betel nut, whereas the other 1 018 chew fresh betel nut. The data were 
statistically analyzed using different variables which included age, number, time of onset of the disease, and the cancerous condition associated with common oral mucosa disease, including oral submucous fibrosis (OSF), oral leukoplakia (OLK), and oral Lichen planus (OLP).</p><p><b>RESULTS</b>1) The study found no significant difference in the prevalence of oral mucosa diseases between the dried betel nut group (n=704) and fresh betel nut group (n=1 018) among the 1 722 cases (P>0.05), but the peak age of oral mucosal disease was more advanced in the dried betel nut group (P<0.01). 2) The incidence within 5 years of OSF, OLK, OLP, and oral mucosa diseases in the dried betel nut group was significantly higher than that in the fresh betel nut group (P<0.01). 3) The incidence of cancer for oral mucosa disease in patients included in the dried betel nut group was significantly higher than that in the fresh betel nut group (P<0.01).</p><p><b>CONCLUSIONS</b>Chewing dried betel nut is more pathogenic and carcinogenic than chewing fresh betel nut. The extremely harmful components of the dried betel nut synergistically play a vital role in the occurrence and carcinogenesis of oral mucosal diseases.</p>

Bioassay-Guided Isolation and Identification of Compounds from Arecae Pericarpium with Anti-inflammatory, Anti-oxidative, and Melanogenesis Inhibition Activities

This study describes the anti-inflammatory, anti-oxidant, and melanogenesis inhibition activities of methanol extract and various organic solvent fractions of Arecae Pericarpium. We examined the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells, 1,1-diphenyl-2-picrylhydrazine (DPPH) scavenging activity, mushroom tyrosinase inhibition activity and melanin contents. The study showed that, among all tested fractions, methylene chloride fraction showed the strongest inhibition of LPS-induced NO production in RAW 264.7 cells (IC₅₀ value 8.89 µg/mL) and DPPH radical scavenging activity (EC₅₀ value 21.39 µg/mL). Methylene chloride and ethyl acetate fractions similarly inhibited mushroom tyrosinase activity. Methanol extract exhibited strongest reduction of melanin content in B16F10 melanoma cells. Based on the bioactivity assay results, methylene chloride and ethyl acetate fractions were further separated. Eight phenolic compounds were isolated, which are dimeric syringol (1), catechol (2), 4-hydroxybenzaldehyde (3), vanillin (4), 4-hydroxyacetophenone (5), apocynin (6), protocatechuic acid (7) and 4-hydroxybenzoic acid (8). Among the isolated compounds tested, catechol showed the strongest inhibition of LPS-induced NO production in RAW 264.7 cells. Catechol also showed the concentration-dependent NF-κB inhibition activity. Arecae Pericarpium might have potentials to be developed as anti-inflammatory agent or dermatological product for skin-whitening agent.

Oral Squamous Cell Carcinoma in Background of Oral Submucous Fibrosis: A Case Report.

Oral submucous fibrosis (OSMF) is a well-recognized, potentially malignant disorder of the oral cavity that can affect any part of the oral mucosa, characterized by mucosal rigidity of varying intensity caused by fibro elastic transformation of the juxta epithelial layer of connective tissue. OSMF occurs in Indians and other population of the Indian subcontinent with certain oral habits. Betel quid chewing is a popular oral habit with potential links to the occurrence of oral cancer. In patients with submucous fibrosis, the oral epithelium becomes atrophic and thereby becomes more vulnerable to carcinogens. Since the ingredients of betel quid, tobacco are crucial for tumor initiation, promotion and progression, exposure to these toxicants simultaneously has been shown to markedly potentiate the oral cancer incidence in OSMF patients. The rate of malignant transformation of OSMF has been estimated to be 2-10%. Most cases with malignant transformation in OSMF have occurred gradually over a long period of time. This paper presents a case of oral submucous fibrosis turning into malignancy in a 34-year-old male patient.

Assessment of Salivary Flow Rate and pH Among Areca Nut Chewers and Oral Submucous Fibrosis Subjects: A Comparative Study

BACKGROUND: To assess and compare the salivary flow rate (SFR) and salivary pH among areca nut chewers, oral submucous fibrosis (OSMF) patients and apparently healthy individuals. METHODS: A comparative study was conducted to assess and compare the SFR and pH among 135 outpatients (45 areca nut chewers + 45 OSMF + 45 control) at The Oxford Dental College and Research Hospital, Bangalore, India. Subjects were interviewed using structural proforma and Modified Schirmer strips and pH paper were implemented for assessing SFR and pH respectively. Statistical analysis was done using IBM SPSS ver. 21.0 software. RESULTS: A statistically significant increase in SFR (35.7 mm at 3rd minutes) among areca nut group and a decrease in SFR among OSMF group (23.4 mm at 3rd minutes) when compared to apparently healthy subjects (30.7 mm at 3rd minutes). The mean pH among areca nut, OSMF and control groups was 6.76, 6.82, and 6.74 respectively with no statistical significance. CONCLUSIONS: The observation and findings of the study clearly showed hypersalivation among areca nut group and hyposalivation among OSMF group, with no significant change in salivary pH when compared to healthy subjects.

Association Between Grading of Oral Submucous Fibrosis With Frequency and Consumption of Areca Nut and Its Derivatives in a Wide Age Group: A Multi-centric Cross Sectional Study From Karachi, Pakistan

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic, premalignant condition of the oral mucosa and one of the commonest potentially malignant disorders amongst the Asian population. The objective of this study was to investigate the association of etiologic factors with: age, frequency, duration of consumption of areca nut and its derivatives, and the severity of clinical manifestations. METHODS: A cross-sectional, multi centric study was conducted over 8 years on clinically diagnosed OSMF cases (n = 765) from both public and private tertiary care centers. Sample size was determined by World Health Organization sample size calculator. Consumption of areca nut in different forms, frequency of daily usage, years of chewing, degree of mouth opening and duration of the condition were recorded. Level of significance was kept at P < or = 0.05. RESULTS: A total of 765 patients of OSMF were examined, of whom 396 (51.8%) were male and 369 (48.2%) female with a mean age of 29.17 years. Mild OSMF was seen in 61 cases (8.0%), moderate OSMF in 353 (46.1%) and severe OSMF in 417 (54.5%) subjects. Areca nut and other derivatives were most frequently consumed and showed significant risk in the severity of OSMF (P < or = 0.0001). Age of the sample and duration of chewing years were also significant (P = 0.012). CONCLUSIONS: The relative risk of OSMF increased with duration and frequency of areca nut consumption especially from an early age of onset.

Rising incidence of oral cancer in Ahmedabad city.

CONTEXT: In 1999, an increase in mouth cancer incidence among young men (<50 years) in urban Ahmedabad was reported to be occurring along with decreasing mouth cancer incidence in older age groups and increasing oral submucous fibrosis incidence associated with areca nut consumption among young men in Gujarat. The aim was to investigate whether the increase in the incidence mouth cancer that had started among young men in the 1990s was continuing. SETTINGS AND DESIGN: Ahmedabad urban population, comparison of reported mouth cancer cases in the population across four time period. METHODS: Age‑specific incidence rates of mouth cancer (International Classification of Diseases [ICD]‑9:143–5; ICD‑10:C03–06) in five year age groups among men aged ≥15 years for the city of Ahmedabad for years 1985, 1995, 2007 and 2010 were extracted from published reports. For comparison, lung cancer (ICD‑9:169; ICD‑10:C33–C34) rates were also abstracted. STATISTICAL ANALYSIS USED: A cohort approach was used for further analysis of mouth cancer incidence. Age adjusted incidence rates of mouth and lung cancer for men aged ≥15 years were calculated and compared. RESULTS: The age specific incidence rates of mouth cancer among men increased over the 25‑year period while lung cancer rates showed a net decrease. Using a cohort approach for mouth cancer, a rapid increase in younger age cohorts was found. CONCLUSIONS: Mouth cancer incidence increased markedly among men in urban Ahmedabad between 1985 and 2010, apparently due to increasing consumption of areca nut products, mawa and gutka. Gutka has now been banned all over India, but a more vigorous implementation is necessary.