Advances in research on pharmacological mechanisms of anatabine: from nicotinic modulation to multitarget therapeutic potential.

Anatabine, a characteristic minor alkaloid derived from tobacco byproducts, exhibits unique structural analogy to nicotine but possesses a superior safety profile and lower addictive liability, rendering it a promising natural multi-target therapeutic candidate. Accumulating preclinical evidence has demonstrated that anatabine exerts neuroprotective, anti-inflammatory, and antioxidant effects mainly through modulating α7/α4β2 nicotinic acetylcholine receptors, suppressing NF-κB/STAT3 inflammatory signaling, and activating the Nrf2-mediated antioxidant pathway. It effectively ameliorates typical pathological alterations, including β-amyloid deposition, tau hyperphosphorylation, and microglial overactivation, thereby improving cognitive and behavioral deficits in neurodegenerative disease models. Additionally, anatabine displays broad pharmacological potentials in chronic inflammation, autoimmune thyroiditis, asthma, and hypertension. Differing from previous reviews that merely focused on single receptor regulation, the present work systematically summarizes the multi-target pharmacological characteristics of anatabine, comprehensively collates its preclinical efficacy across multiple disease categories, and highlights its advantages over nicotine in safety and addiction risk. Furthermore, we analyze the current limitations, druggability optimization challenges, and clinical translation prospects, and propose sustainable strategies for high-value utilization of tobacco byproducts. This review provides an updated and systematic theoretical basis for further mechanism exploration and therapeutic development of anatabine.