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.
Peptidyl-Dipeptidase A ; Areca ; Hypertension

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.
Areca ; Arecoline/analysis* ; Drugs, Chinese Herbal/analysis* ; Kinetics ; Seeds/chemistry* ; Water/analysis*

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.
Antioxidants/pharmacology* ; Areca/chemistry* ; Humans ; Hypoxia ; Oxidative Stress ; Polyphenols/pharmacology* ; Superoxide Dismutase/metabolism*

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.
Areca ; China ; Drugs, Chinese Herbal/adverse effects* ; Seeds ; Semen

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.
Areca ; Autophagy ; Humans ; Mouth Neoplasms ; Nuts ; Oral Submucous Fibrosis ; Reactive Oxygen Species

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.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Areca ; Beijing ; Female ; Humans ; Male ; Mastication ; Middle Aged ; Mouth Neoplasms ; Risk Factors ; Smoking ; Young Adult

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 ; adverse effects ; Bibliometrics ; China ; epidemiology ; Humans ; Malaysia ; epidemiology ; Mouth Neoplasms ; epidemiology ; Risk Factors ; United Kingdom ; epidemiology

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.
Acute Coronary Syndrome* ; Areca* ; Asia, Southeastern ; Cardiovascular Diseases ; Cohort Studies ; Esophageal Neoplasms ; Follow-Up Studies ; Humans ; Hypertension ; Mass Screening ; Mastication* ; Mortality* ; Nuts* ; Pakistan* ; Proportional Hazards Models ; Prospective Studies

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.
Activation, Metabolic ; Areca ; Asian Continental Ancestry Group ; Cytochrome P-450 Enzyme System ; Deglutition ; DNA ; DNA Damage ; Epithelium ; Female ; Fibroblasts ; Fibrosis ; Humans ; Incidence ; Lobeline* ; Male ; Mastication ; Mouth ; Mouth Neoplasms* ; Nicotine ; Nitrosamines ; Nuts ; Oral Submucous Fibrosis ; Prevalence* ; Reactive Oxygen Species ; Risk Factors ; RNA ; Tobacco ; Tobacco, Smokeless*

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.
Activation, Metabolic ; Areca ; Asian Continental Ancestry Group ; Cytochrome P-450 Enzyme System ; Deglutition ; DNA ; DNA Damage ; Epithelium ; Female ; Fibroblasts ; Fibrosis ; Humans ; Incidence ; Lobeline ; Male ; Mastication ; Mouth ; Mouth Neoplasms ; Nicotine ; Nitrosamines ; Nuts ; Oral Submucous Fibrosis ; Prevalence ; Reactive Oxygen Species ; Risk Factors ; RNA ; Tobacco ; Tobacco, Smokeless