Chewing areca nuts is a popular hobby in the Asian region, and areca nuts are rich in polyphenols, although some alkaloids are included. In this study, we explored the antioxidant activity of areca nut polyphenols (ANP) in lipopolysaccharides (LPS)-stimulated RAW264.7 cells. The results revealed that ANP reduced the level of reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells and enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). RNA-seq analysis showed that ANP down-regulated the transcription of genes related to the cancer pathway at 160 μg/mL, and the inflammatory pathway as well as viral infection pathway at 320 μg/mL. The cellular signaling analysis further revealed that the expressions of these genes were regulated by the mitogen-activated protein kinase (MAPK) pathway, and ANP downregulated the activation of the MAPK signaling pathway stimulated by LPS. Collectively, our findings showed that ANP inhibited the MAPK pathway and activated the Nrf2/HO-1 antioxidant pathways to reduce ROS generation induced by LPS.

A number of reports of the effects of garlic on gut microbiota revealed that the active garlic organosulfur compounds (OSCs) are destabilized by the action of alliinase during garlic preparation. In this study, garlic alliinase was deactivated to obtain stable garlic OSCs. Experiments with C57BL/6J mice fed with lipid and glucose metabolic disorder-inducing Western diet (WD) revealed that stable garlic OSCs prevented the disorder by increasing the relative abundance of gut Bacteroides acidifaciens. Molecular analysis indicated that garlic OSCs inhibited dyslipidemia and fatty liver by increasing taurine and subsequently promoting hepatic fatty acid β-oxidation. In parallel, garlic OSCs could meliorate glucose homeostasis by inhibiting dipeptidyl peptidase-4 (DPP-4) and hepatic gluconeogenesis. In vitro bacterial culture experiments revealed that garlic OSCs directly increased the growth of gut Bacteroides acidifaciens. The results of this study demonstrate that the molecular mechanism of the preventive effect of garlic OSCs on the WD-induced metabolic disorder is attributed to the enhanced growth of Bacteroides acidifaciens and the consequent increase in taurine.

To analyze oral microbial diversity in the saliva of 8 healthy individuals before and after chewing areca nuts. Saliva samples were collected before chewing areca nuts, after chewing areca nuts for 5 min and after chewing areca nuts for 30 min. DNA was extracted, and microbial diversity was examined using PCR-denaturing gradient gel electrophoresis (PCR-DGGE). When examining DGGE profiles collectively, the bands associated with Streptococcus and Veillonella were the most intense, making them the most prevalent bacteria. Furthermore, the band intensities did not decrease after chewing areca nuts for 5 or 30 min; thus, these bacteria were unaffected. However, when examining some individuals, the band intensities for Streptococcus and Veillonella became more intense after 5 min of chewing and then returned to the pre-chewing level. This difference may be attributed to the mechanical movements of the oral cavity or individual differences. Other bacteria, such as Neisseria, Actinomycetes, and Rothia dentocariosa, were also found to have an increased or decreased prevalence following areca nut-chewing. Since the predominant species that are present following areca nut-chewing include Streptococcus and Veillonella, it would seem likely that these bacteria play an important role in the periodontal diseases associated with areca chewing.

The chewing of areca nut is closely associated with human diseases such as oral submucous fibrosis and immune related diseases. Recent studies have focused on the pharmacological and toxicological effects of areca nut chewing, and have largely overlooked the effects on intestinal microbiota. In this study, we sought to understand how different methods of areca consumption affect intestinal microflora composition. A total of 60 male and 60 female Kunming mice were each randomly divided into six groups and fed different areca preparations to mimic different areca nut chewing habits. The preparations included fresh areca fruit; areca fruit with betel leaf or cured tobacco; brined areca; smoked brined areca; and a control. The fecal microbiota of mice in the 12 groups was compared after 28 days of oral gavage administration. To determine the composition and diversity of the fecal microbiota, we performed high‐throughput sequencing of bacterial 16S rRNA. In both male and female mice, the diversity and abundance of the intestinal microbiota of the experimental groups were higher than those in the control groups. Furthermore, different areca preparations had different effects on the diversity, abundance, and composition of the intestinal flora of Kunming mice. Practical applications The chewing of areca nuts in various forms is widespread in Asia and other areas. This manuscript first explores the effects of different areca nut chewing habits on the gut microbiota of mice. We then further clarify the impact of different areca nut chewing habits on intestinal health and provide a new direction for areca nut research. In addition, our findings will increase public understanding of areca nut usage and provide guidance for the areca nut industry.

The areca nut is often consumed as a chewing food in the Asian region. Our previous study revealed that the areca nut is rich in polyphenols with high antioxidant activity. In this study, we further assessed the effects and molecular mechanisms of the areca nut and its major ingredients on a Western diet-induced mice dyslipidemia model. Male C57BL/6N mice were divided into five groups and fed with a normal diet (ND), Western diet (WD), WD with areca nut extracts (ANE), areca nut polyphenols (ANP), and arecoline (ARE) for 12 weeks. The results revealed that ANP significantly reduced WD-induced body weight, liver weight, epididymal fat, and liver total lipid. Serum biomarkers showed that ANP ameliorated WD-enhanced total cholesterol and non-high-density lipoprotein (non-HDL). Moreover, analysis of cellular signaling pathways revealed that sterol regulatory element-binding protein 2 (SREBP2) and enzyme 3-hydroxy-3-methylglutaryld coenzyme A reductase (HMGCR) were significantly downregulated by ANP. The results of gut microbiota analysis revealed that ANP increased the abundance of beneficial bacterium Akkermansias and decreased the abundance of the pathogenic bacterium Ruminococcus while ARE shown the opposite result to ANP. In summary, our data indicated that areca nut polyphenol ameliorated WD-induced dyslipidemia by increasing the abundance of beneficial bacteria in the gut microbiota and reducing the expressions of SREBP2 and HMGCR while areca nut ARE inhibited this improvement potential.