Effects Of Areca Nut Research Articles

Oral Submucous Fibrosis - Case Series

Oralsubmucous fibrosis is regarded as a collagen metabolic disorder with an overall increased collagen production and decreased collagen degradation resulting in increased collagen deposition in the oral tissues, and fibrosis due to alkaloid exposure. We report three case reports of oral submucous fibrosis. Clinical findings and histopathologic findings were consistent with the diagnosis of stage 2 oral submucous fibrosis. The patient was educated on the effects of areca nut and chances of malignant transformation. Keywords Malignant Transformation, Oral Submucous Fibrosis, Pathogenesis, Management

Biological Effects and Biomedical Applications of Areca Nut and Its Extract.

The dried, mature fruit of the palm tree species Areca catechu L. is known as the areca nut (AN) or betel nut. It is widely cultivated in the tropical regions. In many nations, AN is utilized for traditional herbal treatments or social activities. AN has historically been used to address various health issues, such as diarrhea, arthritis, dyspepsia, malaria, and so on. In this review, we have conducted a comprehensive summary of the biological effects and biomedical applications of AN and its extracts. Initially, we provided an overview of the constituents in AN extract. Subsequently, we summarized the biological effects of AN and its extracts on the digestive system, nervous system, and circulatory system. And we elucidated the contributions of AN and its extracts in antidepressant, anti-inflammatory, antioxidant, and antibacterial applications. Finally, we have discussed the challenges and future perspectives regarding the utilization of AN and its extracts as emerging pharmaceuticals or valuable adjuncts within the pharmaceutical field.

Chemical Composition of Areca Nut and Its Adverse Effects on Human Health.

Areca nut (AN) is one of the addictive substances consumed widely in the world. The composition of AN is very complex, and each component has variable properties. This study aimsto review the composition of AN and its adverse effects on humans. For this review, the literature search was performed by an electronic search of the Pubmed/Medline, Scopus, and Google Scholar databases using proper MESH headings and retrieved the articles published from 1997 to 2022. The eligibility criteria included human studies, a form of AN, the composition of AN, harmful effects of AN, the effect of AN on the oral cavity,the effect of AN on vital organs, and articles published in English. Data were extracted regarding the composition of AN, forms of AN, and harmful effects of AN on the oral cavity and on other systems. A total of 449 articles were identified from various databases, and 36 studies were selected that met the inclusion criteria. The active components of AN, which produce harmful effects, are primarily alkaloids, polyphenols, tannins, and certain trace elements. AN is consumed in different forms, and based on the form, its composition also varies. AN is known to cause deleterious effects on the oral cavity as well as various body organs. The most dangerous and widely reported impacts of AN on the oral cavity are the development of oral submucous fibrosis, a premalignant condition, and oral malignancy.However, during the chewing process, excretory products of AN are released and circulate in the body of "chronic habitual" and affect the other body parts. Thus, AN consumption may contribute to cardiac, liver, endocrinal, metabolic, respiratory, and reproductive system disorders also. AN composition is complex, and its consumption is harmful to human health. In regard to controlling the issue of the harmful effects of this habit, preventive measures should be established.

The Controversial Roles of Areca Nut: Medicine or Toxin?

Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was used as early as about A.D. 25-220 as a remedy. Traditionally, AN was applied for several medicinal functions. However, it was also reported to have toxicological effects. In this review article, we updated recent trends of research in addition to acquire new knowledge about AN. First, the history of AN usage from ancient years was described. Then, the chemical components of AN and their biological functions was compared; arecoline is an especially important compound in AN. AN extract has different effects caused by different components. Thus, the dual effects of AN with pharmacological and toxicological effects were summarized. Finally, we described perspectives, trends and challenges of AN. It will provide the insight of removing or modifying the toxic compounds of AN extractions for enhancing their pharmacological activity to treat several diseases in future applications.

Prevalence, Habit Pattern, and Awareness on Harmful Effects of Tobacco/Areca Nut Use among Patients Visiting a Tertiary Care Center in Sri Lanka.

S.P. Kalpana Jeewanthi SubasingheBackground The carcinogenicity of tobacco and areca nut is well established worldwide. Areca nut is the fourth most common psychoactive substance identified recently. The effects of areca nut on the autonomic nervous system make the users dependent on the habit which has been an emerging health issue among Sri Lankan adults and adolescents. This study aimed to evaluate the prevalence and patterns of these risk habits among the patients attending a tertiary care center in Sri Lanka, and their awareness of the harmful effects of the habit. Method A hospital-based cross-sectional study was conducted among 512 patients using an interviewer-administered questionnaire. Results The sample consisted of 167 (33%) tobacco consumers. The average age of the initiation of tobacco consumption was 23.66 years (standard deviation ± 8.04). Age ( p = 0.001), gender ( p = 0.001), income ( p = 0.005), and educational level ( p = 0.001) are significantly associated with tobacco consumption. There is a strong likelihood for tobacco consumers to consume areca nut (odds ratio [OR] 30.58, 95% confidence interval [CI] 17.05-54.88) and alcohol (OR 11.16, 95% CI 6.91-17.98) at any stage in their lives. The majority of the tobacco consumers (61%) were smokeless tobacco users. Areca nut consumers are 0.44 times more likely to know its carcinogenic effects than nonconsumers (95% CI 0.28-0.69). Tobacco consumers are more likely to be aware of the harmful effects of tobacco consumption than nonconsumers (OR 1.11, 95% CI 0.45-2.74). Sixty percent have made at least one attempt to quit the habit. Sixty-two percent of the unsuccessful quitters reported the reason as "addiction." Conclusion Prevalence of smokeless tobacco consumption prevails at a high level among Sri Lankans. Tobacco and areca nut users are more likely to be aware of its harmful effects than the nonconsumers but unable to quit the habit due to the psychoactive properties of tobacco and areca nut.

Oral submucous fibrosis: A case report and contemporary review of pathogenesis

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder characterized by fibroelastic changes in the juxta-epithelial layer leading to trismus. Areca nut and its metabolites contribute to the etiopathogenesis. We report a case of a 53-year-old male patient with burning sensation and reduced mouth opening. Clinical findings and histopathologic findings were consistent with the diagnosis of OSF – intermediate stage. The patient was conservatively managed with lycopene 4 mg twice daily for 3 months and also advised oral physiotherapy. The patient was educated on the effects of areca nut and chances of malignant transformation.

Knowledge and Attitudes of Nursing Students Towards Smokeless Tobacco and Areca Nut Control in Central Province of Sri Lanka

Background: Use of smokeless tobacco (SLT) and areca nut (AN) is widespread in Sri Lanka. Several workshops to train healthcare workers on SLT/ AN cessation programmes (SLT/AN-CP) were carried out. Objective of the study was to evaluate the enhancement of knowledge and attitudes related to SLT/AN-CP among nursing students following a workshop. Methods: A cross sectional study was conducted with the use of two questionnaires. A total of 212 nursing students were assessed and the study group included 184 females (86.8%). Results: Results were analyzed according to the 3 main areas of the assessment, i.e knowledge related to Oral cancer, knowledge related to SLT, its effects and cessation practices and attitudes regarding SLT cessation counselling. Out of the eight questions to assess the knowledge related to oral cancer, five questions demonstrated a statistically significant difference (P<0.05) following the workshop when compared to the pre workshop knowledge. Even though, majority had a good knowledge on harmful effects of SLT and AN, it was interesting to note that 14.15 % of the participants were unaware about the fact that the oral cancer is the commonest cancer among Sri Lankan males. 96.7% agreed that proper counseling would lead patient to quit the habit. Conclusions: This preliminary study showed that the knowledge and attitude towards SLT/AN-CP among nursing students were satisfactory and effective workshops can be used to improve their knowledge and attitudes towards SLT/AN-CP especially in low economical settings

Smokeless tobacco ‘sadagura’ and areca nut extract exposure induces extensive embryotoxicity in chick embryo, Gallus gallus domesticus

Areca nut (AN) and sadagura (SG, homemade smokeless tobacco) are often consumed alone or in combination irrespective of gender including pregnant women in the southern region of Assam, India. However, very few studies have been carried out so far to evaluate its ill effect during embryogenesis. The present study aims to determine the effects of AN, SG, and combination of both (AN + SG) in developing chick embryos as it serves as an excellent model for teratogenic and developmental toxicity study owing to its similarity with the human embryo. Fertile White Leghorn chicken eggs (Gallus gallus domestucus) were exposed to different concentrations of 0.125, 0.25, 0.5, and 1 mg/egg of AN, SG, and AN + SG extract, respectively. The eggs were divided into four groups: control, AN extract-, SG extract-, and AN + SG-treated group. Three different parameters, viz. mortality rate, morphometric measurements, and qualitative anomalies, were studied to observe teratogenic effects. Results indicated a dose-dependent increase in mortality rate in all the treatment groups. Also, quantitative measures suggested significant decrease (p < 0.001) in wet body weight, crown–rump length, anterior–posterior head length, and eyeball diameter in all the concentration of AN, SG and AN + SG of treatment groups when compared to control group. Compared to control, anomalies like microcephaly, microphthalmia, deformed beak, hemorrhage, omphalocele, flexed limbs, and ectopia cordis were prominent in treated groups. Our findings depict organ-specific as well as systemic defects in the developing embryos. Our results suggest that exposure to AN, SG, and AN + SG causes adverse developmental abnormalities and embryo mortality in the chick embryo.

Barriers to Quitting Areca Nut Consumption and Joining a Cessation Program as Perceived by Chewer and Nonchewer Populations in Guam

Background: Areca nut (AN) is a carcinogenic substance consumed by roughly 600 million individuals worldwide with increasing popularity in Guam. In response, a cessation program was developed and implemented in Guam and Saipan. However, to improve its delivery, it is necessary to understand the reasons influencing recruitment and participation, such as why a chewer may not want to quit or join a cessation program. Objective: To explore barriers inhibiting chewers from quitting AN chewing and from participating in a cessation program. Methods: Nine individual and group discussions were facilitated with a convenience sample of 17 chewers and nonchewers in Guam in 2017. The mean age of the participants was 36.4 years. Recurring themes relating to reasons for not quitting and not joining a cessation program were extracted. Results: Results produced three general categories—Sociocultural, Behavioral, and Accessible. Each category encompasses different attributes concerning reasons not to quit chewing (e.g. addiction, enabling community, or belief that AN is harmless), and reasons influencing lack of participation in a cessation program (e.g. time, transportation, or relatability). Conclusions: Current findings suggest chewers are unaware of the harmful effects of AN. Also, they may not comprehend the purpose of a cessation program. In addition, the likelihood of chewers participating in a cessation program is influenced by their level of comfort with the program and personnel, and whether a program addresses their time and transportation limitations.

Areca nut trade, globalisation and its health impact: perspectives from India and South-east Asia.

Areca nut (AN) is consumed globally by 600 million people, and 10%-20% of the world population uses betel quid, a preparation containing areca nut. India and other South-east Asian countries are the largest consumers of AN in the world. The aim of this article is to review the economic impact and oral health effects of the consumption of AN. It will also discuss the role of dentists and auxiliary healthcare providers for increasing public awareness and the need for a strong public health policy. To address the concerned area, PubMed, Scopus and Google Scholar databases were explored from the year 1965 until 2017. Studies focusing on various aspects of AN only, and articles published in English were included. Anecdotal reports, case reports and unpublished data were excluded. This narrative review suggests India is the world's largest producer of AN along with the largest AN consuming population followed by other South-east Asian countries. AN chewing causes oral submucous fibrosis (OSF) and it is most commonly observed in people of India and South-east Asia. AN use is associated with various social and unsocial aspects. Dentists and dental auxiliaries can increase the knowledge and awareness of a health issue (OSF) among the target audience as well as the detrimental effects of AN chewing. There is a need for more aggressive public health measures and dentists and dental auxiliaries should be employed to bring awareness to the general public regarding AN use.

The Substance Basis Research of Stir-Baking to Dark Brown Could Enhance the Promoting Effects of Areca Nut on Gastrointestinal Motility

The promoting effects of areca nut (AN) and charred areca nut (CAN) on gastrointestinal motility were compared. The HPLC analysis was used to compare the constituents in AN and CAN and the new produced constituents in CAN were isolated and identified. Then the promoting effects of the identified constituents on gastrointestinal motility were investigated in vivo. In the results, CAN showed stronger promoting effect on gastrointestinal motility than that of AN (P < 0.05) in vivo and in vitro. Three new constituents in CAN were identified as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone (DDMP), 5-hydroxymethyl-2-furfural (5-HMF) and 3-hydroxy-2-methyl-γ-pyrone (maltol). Interestingly, AN combined with the constituents (DDMP : 5-HMF : maltol = 30:355:21) showed a synergistic effect on promoting gastrointestinal motility. In conclusion, the results indicated that Maillard reaction products (MRPs) might be the substance basis of stir-baking to dark brown enhances the promoting effects of AN on gastrointestinal motility. Practical Applications Stir-baking to dark brown is a common processing technique of Traditional Chinese Medicine (TCM) in China. AN is usually processed by stir-baking to dark brown to CAN before clinical use, because CAN was considered to be specialized in treating digestive disorders. The present study proved that stir-baking to dark brown could enhance the promoting effects of AN on gastrointestinal motility. Furthermore, our investigation provided substance basis for clinical application of CAN regarding the digestive activity and will be conducive to further development of this drug.

Abstract 824: A novel mechanism of areca nut-induced oral cancer is through the conversion of cancer stem cells to acquire malignant phenotypes

Abstract Areca nut is one of the most commonly used psychoactive substance worldwide. It is has been identified as a primary carcinogen of oral cancer in Southeast Asia. Previous studies to examine the effects of this carcinogen often used short-term and high-dose treatment of area nut extract (ANE) as a research model. To elucidate the molecular effects of areca nut and mimic patient chronic exposure situation, we established four areca nut extract (ANE)-trained oral cancer sublines by treating cells with low-dose of ANE (IC30, dose for 30% growth inhibition) for 2 months. Without evidence of cellular senescence, these sublines exhibited significant increases in invasive ability, along with the up-regulation of MMP1 and the reversed expression of epithelial-mesenchymal transition markers. These sublines also showed more resistant to chemotherapeutics and irradiation, which was associated with the over-expression of ABCG2 transporters, increased production of anti-oxidative enzymes, and insensitive to ROS induction. Furthermore, these chronically treated cells possessed characteristics of cancer stem cells, as indicated by enrichment of CD24-/CD44+ population, enhancing spheroid cell formation, and increasing expressions of stemness associated molecules, including Slug, Twist1, Sox9, and Grp78. Thus, we concluded that chronic areca nut exposure induces a pleotropic effect on stemness regulators that facilitates the conversion of cancer stem cells to acquire malignant transformation in oral cancer. This novel finding provides valuable knowledge on areca nut-induced oral carcinogenesis. Citation Format: Yi-Chen Li, Ann-Joy Cheng. A novel mechanism of areca nut-induced oral cancer is through the conversion of cancer stem cells to acquire malignant phenotypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 824. doi:10.1158/1538-7445.AM2015-824

Modulation of Phagocytosis, Chemotaxis, and Adhesion of Neutrophils by Areca Nut Extracts

A higher prevalence of periodontal diseases among areca chewers than non-areca chewers has been demonstrated. Neutrophils, representing the first line of the host defense mechanism against microbial infection, play important roles in maintaining periodontal health. This study determined the possible effects of areca nut on phagocytosis, chemotaxis, and adhesion of human neutrophils. Aqueous extracts of ripe areca nut without husk (rANE) and fresh and tender areca nut with husk (tANE) were examined for their effects on neutrophil phagocytosis using flow cytometry and confocal laser scanning microscopy. The effects of rANE and tANE on chemotaxis and adhesion of neutrophils to human aortic endothelial cells were examined using fluorescence-labeled neutrophils. Both rANE and tANE inhibited the phagocytic activity of neutrophils in a dose-dependent manner. The levels of internalized fluorescent bacteria in neutrophils decreased after ANE treatment. However, exposure of neutrophils to rANE and tANE stimulated the chemotaxis activity of neutrophils to N-formyl-Met-Leu-Phe (fMLP) and enhanced adhesion of neutrophils to human aortic endothelial cells in a dose-dependent manner. Moreover, treatment of neutrophils with rANE was more effective than incubation with tANE. Components of areca nut inhibited phagocytosis activity of neutrophils but enhanced chemotaxis and adhesion of neutrophils. Alterations in functions of neutrophils may lead to signs of clinical diseases associated with areca chewing. The components in ANEs that are responsible for these observations remain to be elucidated.

Areca nut, energy metabolism and hunger in Asian men

Background : The nut of the Areca catechu palm has long been attributed effects on hunger and the digestive process. Objectives : The objectives were to assess experimentally effects of areca nut on fasting and postprandial energy metabolism, substrate utilization and hunger. Subjects and methods : Two randomized, placebo-controlled, double-blind studies were undertaken. In study 1, eight Indian men received bioadhesive gels delivering 0, 5, 10 or 20 mg arecoline to the buccal sulcus after an overnight fast. Resting energy expenditure and substrate utilization were determined by ventilated hood calorimetry over 6 h during which hunger was rated on five occasions. In study 2, 15 Indian men received gels delivering 0 or 10 mg arecoline after consuming a 2.5 MJ meal, and the same protocol was then applied as in study 1. Results : Fasting resting energy expenditures exceeded basal metabolic rate (BMR) by 5.4 - 0.8% (Mean - SE) after placebo, and 5.1 - 0.7% after 20 mg arecoline, but by 0.9 - 0.8% and 0.7 - 0.5% following 5 mg and 10 mg arecoline, respectively. Carbohydrate (CHO) utilization rates rose after areca nut compared to placebo (F 3,252 = 7.3, p < 0.001). Hunger varied across doses ( h 2 = 10.5, p < 0.02), being lowest after 10 mg and highest after 20 mg, and was influenced by interaction of dose with delta resting energy expenditure. In study 2, areca dose interacted with fat-free mass (FFM) to lower by 5.4 - 11.2% the thermic effect of a meal (F 1,28 = 4.9, p = 0.05), and retarded peak 'digestive-phase' thermogenesis by 60 min (F 1,58 = 5.7, p = 0.02). Postprandial delta CHO utilization was greater (F 1,28 = 4.5, p = 0.05), and hunger was lower ( h : 2 = 3.8, p = 0.05), after areca nut. The areca nut altered relationships of hunger to thermic effects of the meal, and to delta substrate utilization, in ways consistent with appetite suppression. Conclusion : Areca nut constituents modulate metabolic signals regulating appetite in man. This concurs with customary belief.

Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase

There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B 2 (TXB 2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB 2 and prostaglandin-D 2 (PGD 2) production. PBL extract also inhibited platelet TXB 2 and PGD 2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O 2 •− and OH, and inhibits xanthine oxidase activity and the OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB 2 production. Indomethacin, genistein, and PBL extract inhibited only TXB 2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB 2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB 2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB 2 and PGD 2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.

Areca nut extract inhibits the growth, attachment, and matrix protein synthesis of cultured human gingival fibroblasts.

Betel quid chewing is a popular oral habit in India, South Africa, and many Southeast Asian countries. The effects of areca nut (AN) extract on the growth, attachment, and protein synthesis of healthy human gingival fibroblasts (GF) were investigated to determine why betel quid (BQ) chewers have higher prevalence of periodontal disease than non-chewers. Twenty-four hour exposure of human GF to AN extract (> 200 microg/ml) in culture led to the formation of numerous intracellular vacuoles. As analyzed by modified MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay, AN extract significantly suppressed the growth of GF over 5 days of incubation in a dose-dependent manner. At concentrations of 50 and 300 microg/ml, AN extract suppressed the growth of GF with 30% and 57% (P < 0.05), respectively. AN extract also significantly suppressed the synthesis of [3H]proline incorporation into trichloroacetic acid (TCA) precipitated proteins. At concentrations of 200, 400, and 600 microg/ml, AN extract suppressed the protein synthesis with 33%, 58%, and 63% of inhibition (P < 0.05), respectively. Preincubation of cells in a medium containing AN extract for 2 hours inhibits the subsequent attachment of cultured GF to type I collagen at the 50% inhibitory concentration (IC50) which is about 720 to 798 microg/ml. Considering the frequent consumption of BQ throughout the day, impairment of sequential fibroblast functions by BQ ingredients is a potential mechanism through which BQ chewing exert a deleterious effect to the gingival tissues.

Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells.

Because the high incidence of oral cancers in South-East Asia is causally linked to the common habit of betel quid chewing, the effects of an aqueous extract of areca nut, one of the main ingredients of the quid, on growth, differentiation, morphology and DNA damage were studied in cultured human buccal epithelial cells. An acute exposure (3 hr) of the cells to the extract altered their morphology and induced ridges in the plasma membrane, with indications of internalization of extract particles. Such exposure also caused formation of DNA single-strand breaks which accumulated during post-treatment culture, indicating continuous exposure to residual particles and/or the possibility of inhibited DNA repair. The extract accelerated terminal differentiation of the cells, measured as involucrin expression at relatively non-toxic levels. The extract caused similar loss of colony-forming efficiency in normal cells and in a buccal carcinoma cell line (SqCC/YI) which was defective in its ability to undergo differentiation, indicating that extract toxicity could occur independently from this response. Finally, the genotoxicity of the salivary areca-nut-specific carcinogen 3-(N-nitrosomethyl-amino)propionaldehyde, was demonstrated by the formation of DNA protein cross-links and DNA single-strand breaks in normal buccal epithelial cells. These findings in vitro suggest that betel quid carcinogenesis in the human oral cavity may involve cytopathic alterations of normal cell morphology, growth and differentiation, as well as formation of DNA damage by areca-nut-related agents extracted or formed in saliva.