A review of the traditional uses, pharmacology, and toxicology of areca nut

Background: Areca nut, the fruit of A. catechu, is an important Chinese herbal medicine and is the first of China's "four southern medicines". The main chemical components are alkaloids, phenols, polysaccharides, amino acids, and terpenoids. The flowers, leaves, fruits and seeds of A. catechu contain high medicinal value. However, with the emergence of adverse reactions in people who chew areca nut, people have doubts about the safety of the use of areca nut. Purpose: In view of the two sides of pharmacology and toxicology of areca nut, this study comprehensively reviewed the components of different parts of A. catechu, the mechanism of pharmacology and toxicology, and the relationship between dosage and pharmacology and toxicology, in order to provide a new reference for the safe application of areca nut. Methods: We used "Areca nut", "Betel nut", and known biologically active ingredients in areca nut, combined with "natural active ingredients", "pharmacological activity", and "toxicological effect" as keywords to search in PubMed, Web of Science, Science Direct and CNKI up to March 2024. Results: A large number of studies have shown that low-dose areca nut has pharmacological effects such as deworming, anti-inflammatory, improving gastrointestinal function, lowering blood lipids, preventing atherosclerosis, anti-depression properties. The important mechanism involved in these effects is to reduce the generation of ROS, inhibit the activation of NADPH oxidase, increase the activity of antioxidant enzymes, affect MAPK, AKT, TLR, NF-kappa B, Nrf-2, PI3 K, STAT3 signaling pathway, reduce COX-2, IL-1 beta m RNA, MCP-1 and ICAM1 mRNA gene expression, reduce IL-6, IL-8, IGE levels, activate AMPK signaling pathway, change the ion level in cells, and increase Bax/Bcl-2 ratio. It interferes with the biochemical metabolic process of bacteria. Long-term consumption of areca nut in large quantities will cause some adverse reactions or related malignant diseases to the human body. Conclusion: We reviewed the pharmacological and toxicological effects and related mechanisms of areca nut, revealed the relationship between dose and pharmacological and toxicological effects, and discussed how to reduce the toxicity of areca nut and improve the comprehensive utilization of areca nut. It provides a reference for the study of the relationship between areca nut and human health, as well as the safe and rational use and full development and utilization of areca nut.