Recent Advance on Biological Activity and Toxicity of Arecoline in Edible Areca (Betel) Nut: A Review

Areca nut (Areca catechu L. AN), which is the dried, mature seed of the palm species Areca catechu L., is consumed by over 600 million individuals, predominantly in South Asia, East Africa, and certain regions of the tropical Pacific. The International Agency for Research on Cancer (IARC) has classified it as a species carcinogenic to humans and designated it as a Group 1 human carcinogen. Arecoline, which has attracted attention for its therapeutic potential in the treatment of mental illness and the relief of gastrointestinal disorders, is the main active alkaloid in the areca nut. However, in 2020, the IARC said that arecoline might be a “probable human carcinogen”. Arecoline can cause various types of cellular damage, primarily leading to the destruction of cell morphology, reduced survival rates, abnormal physiological functions, and even cell apoptosis. The research on its toxic mechanisms includes several aspects, such as increased levels of reactive oxygen species, autophagy, epigenetic dysregulation, and immune dysfunction, but these research findings are scattered and lack systematic integration. This article summarizes the effect mechanisms of arecoline on the oral cavity, neurological and cardiovascular systems, and other organs, as well as embryogenesis, and provides detailed and valuable insights for the clinical practice and targeted therapy of arecoline.