Chemistry, metabolism and pharmacology of carcinogenic alkaloids present in areca nut and factors affecting their concentration

Gupta, AK; Tulsyan, Sonam; Thakur, Nisha; Sharma, Vishwas; Sinha, Dhirendra N; Mehrotra, Ravi

doi:10.1016/j.yrtph.2019.104548

Cited by 47 publications

(34 citation statements)

References 112 publications

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“…Results from this study imply the association of low SES with chewing habits and late stage presentation supported by different studies. Areca nut is the fourth most common psychoactive substance used in the world [45] and habitual areca nut chewers present with more aggressive cancer phenotypes, high rates of metastasized cancer, recurrence, and poor patient survival [46]. Though the association of areca nut chewing with late stage tumor remains largely unexplored, this is just an observation with no definite answers.…”

Section: Plos Onementioning

confidence: 99%

“…However, it is speculated that people tend to keep areca nut in the mouth for a longer period simply because it is hard wood-like stuff which does take a long time to chew, and in contrast to other products, its extract is sucked. As little as microgram quantity of this extract has shown to be needed for any cytotoxic or genotoxic event resulting in disease progression [45,47]. Patients with low SES are not only at higher risk of developing OSCC, but are also to be diagnosed at late stage [48].…”

Section: Plos Onementioning

confidence: 99%

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Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan

et al. 2020

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Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is the first and second most common cancer in males and females of Pakistan respectively. Major risk factors include peculiar chewing habits like areca nut, betel quid, and tobacco. The majority of OSCC presents at an advanced stage with poor prognosis. On the face of such a high burden of this preventable cancer, there is a relative lack of recent robust data and its association with known risk factors from Pakistan. The aim of this study was to identify the socioeconomic factors and clinicopathological features that may contribute to the development of OSCC. A total of 186 patients diagnosed and treated at a tertiary care hospital, Karachi Pakistan were recruited. Clinicopathological and socioeconomic information was obtained on a structured questionnaire. Descriptive analysis was done for demographics and socioeconomic status (SES) while regression analysis was performed to evaluate the association between SES and chewing habits, tumor site, and tumor stage. The majority of patients were males and the mean age of OSCC patients was 47.62±12.18 years. Most of the patients belonged to low SES (68.3%) and 77.4% were habitual of chewing. Gender (male) and SES were significantly associated with chewing habits (p<0.05). Odds of developing buccal mucosa tumors in chewers (of any type of substance) and gutka users were 2 and 4 times higher than non-chewers respectively. Middle age, chewing habits, and occupation were significantly associated with late stage presentation of OSCC (p<0.05). In conclusion, male patients belonging to low SES in their forties who had chewing habits for years constituted the bulk of OSCC. Buccal mucosa was the most common site in chewers and the majority presented with late stage tumors.

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Section: Plos Onementioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan

et al. 2020

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“…Due to the presence of calcium oxide, arecoline and guvacoline are hydrolyzed to arecaidine and guvacine, respectively, in basic conditions [ 163 , 164 ]. Areca alkaloids mediate the autonomic responses of the parasympathetic nervous system and the synaptic transmission in the peripheral nervous system [ 164 , 165 , 166 ], and impact various aspects of brain function and regulation [ 167 , 168 ]. Arecoline is a partial muscarinic (M) agonist and possesses a higher affinity for M receptors than guvacoline [ 24 , 169 ].…”

Section: Discussionmentioning

confidence: 99%

“…High arecoline doses produce nicotinic cholinergic effects [ 170 ]. As tertiary amines, arecoline and, to a lesser extent, arecaidine have a deep brain penetration [ 165 , 169 ]. It was demonstrated that arecoline enhances cognition and memory and significantly improves several behavioral disorders in patients with Alzheimer’s disease or schizophrenia, through the activation of postsynaptic M1 receptors [ 24 , 162 , 171 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacology of Herbal Sexual Enhancers: A Review of Psychiatric and Neurological Adverse Effects

et al. 2020

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Sexual enhancers increase sexual potency, sexual pleasure, or libido. Substances increasing libido alter the concentrations of specific neurotransmitters or sex hormones in the central nervous system. Interestingly, the same pathways are involved in the mechanisms underlying many psychiatric and neurological disorders, and adverse reactions associated with the use of aphrodisiacs are strongly expected. However, sexual enhancers of plant origin have gained popularity over recent years, as natural substances are often regarded as a safer alternative to modern medications and are easily acquired without prescription. We reviewed the psychiatric and neurological adverse effects associated with the consumption of herbal aphrodisiacs Areca catechu L., Argemone Mexicana L., Citrus aurantium L., Eurycoma longifolia Jack., Lepidium meyenii Walp., Mitragyna speciosa Korth., Panax ginseng C. A. Mey, Panax quinquefolius L., Pausinystalia johimbe (K. Schum.) Pierre ex Beille, Piper methysticum G. Forst., Ptychopetalum olacoides Benth., Sceletium tortuosum (L.) N. E. Brown, Turnera diffusa Willd. ex. Schult., Voacanga africana Stapf ex Scott-Elliot, and Withania somnifera (L.) Dunal. A literature search was conducted on the PubMed, Scopus, and Web of Science databases with the aim of identifying all the relevant articles published on the issue up to June 2020. Most of the selected sexual enhancers appeared to be safe at therapeutic doses, although mild to severe adverse effects may occur in cases of overdosing or self-medication with unstandardized products. Drug interactions are more concerning, considering that herbal aphrodisiacs are likely used together with other plant extracts and/or pharmaceuticals. However, few data are available on the side effects of several plants included in this review, and more clinical studies with controlled administrations should be conducted to address this issue.

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“…Further study reported catechin as the most abundant polyphenols compound in AN from Malaysia 22 . Toxicity of AN are more likely contributed by polyphenols 23 . Several identified polyphenols in AN such as safrole, hydroxychavicol, and catechins have been proven as carcinogens 24 , 25 .…”

Section: Introductionmentioning

confidence: 99%

Distinct phenolic, alkaloid and antioxidant profile in betel quids from four regions of Indonesia

Sari

Prayogo

Loo

et al. 2020

Sci Rep

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Betel quid (BQ) is a chewing mixed package that mainly contains areca nut (AN), betel leaf (Leaf) or betel stem inflorescence (SI), and slaked lime, and is consumed with or without tobacco BQ chewing is common in South East Asia and has been strongly associated with malignant and potentially malignant diseases of the oral cavity. Alkaloids such as arecoline are often accounted for the carcinogenic potential of BQ, however the chemical composition of BQ has not been studied in detail. In the current study, we investigated the total phenolic content (TPC), antioxidant activity (by mean of ferric reducing antioxidant power, FRAP), radical scavenging activity (DPPH test), polyphenolic profile and arecoline content in different components of BQ, namely AN, Leaf or SI, Husk, and blended BQ (BQ mix, containing AN, Leaf or SI and slaked lime). Samples were imported from 4 major regions of Indonesia, namely: Banda Aceh (BA), North Sumatra (NS), West Kalimantan (WK) and West Papua (WP). The highest TPC, FRAP, and DPPH values were detected in AN samples compared to other BQ components, while samples from WP region were of higher values compared to the other regions. High performance liquid chromatography—Mass Spectrometry (LC–MS) analysis showed that Husk contains the widest range of polyphenols, including hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols and stilbenes. Catechin and epicatechin were the main polyphenols detected in BQ, and they were present at the highest concentrations in WP–AN sample. Arecoline was detected in all AN and BQ mix samples and was significantly correlated with catechin and epicatechin, and significantly negatively correlated with p-hydroxybenzoic acid. Notably, arecoline concentration changed significantly when AN was blended in BQ mixtures. The current study is the first to extensively characterise the chemical composition of BQ and provides insight for a better understanding of the interactions of BQ alkaloids and phenolics in the development of oral submucous fibrosis and oral cancer.

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Chemistry, metabolism and pharmacology of carcinogenic alkaloids present in areca nut and factors affecting their concentration

Cited by 47 publications

References 112 publications

Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan

Oral cancer: Clinicopathological features and associated risk factors in a high risk population presenting to a major tertiary care center in Pakistan

Pharmacology of Herbal Sexual Enhancers: A Review of Psychiatric and Neurological Adverse Effects

Distinct phenolic, alkaloid and antioxidant profile in betel quids from four regions of Indonesia

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