Amaryllidaceae Alkaloids as Anti-inflammatory Agents Targeting Cholinergic Anti-inflammatory Pathway: Mechanisms and Prospects

Amaryllidaceae alkaloids are well-known for inhibiting acetylcholine esterase and for its representative galanthamine to treat Alzheimer’s disease in clinical practice. Recently galanthamine is known for modulating the cholinergic anti-inflammatory pathway (CAP), in which the parasympathetic vagus nerve inhibits the release of pro-inflammatory cytokine and protects against systemic inflammation during immune challenge. This cholinergic modulation of inflammation involves with the neurotransmission of acetylcholine in the vagus nerve, acetylcholine esterase, alpha 7 subunit of nicotinic acetylcholine receptors (α7nAChR) in macrophages, and pro-inflammatory cytokines in the immune system. All of these involved factors are possible targets for the potential anti-inflammatory action of amaryllidaceae alkaloids. In addition, amaryllidaceae alkaloids inhibit p-38 MAP kinase, NFκB activation, cyclooxygenases, and nitric oxide, all of which are key inflammatory mediators. This chapter focuses on the mechanisms and prospects of four amaryllidaceae alkaloids, galanthamine, lycorine, narciclasine (lycoricidinol), and crinamine for their anti-inflammatory potential targeting CAP. It discusses their molecular and cellular action on the acetylcholine esterase, the vagus nerve, α7nAChR, pro-inflammatory cytokines, p-38 MAP kinase, NFκB, cyclooxygenases, and nitric oxide. Following the discussion, it is clear that amaryllidaceae alkaloids are not only a useful tool for studying the cholinergic anti-inflammatory pathway but also offer a potential as a new class of anti-inflammatory natural products, acting on multiple targets to combat inflammatory disorders and having different modes of action from the classical nonsteroidal anti-inflammatory drugs.