Eur J Pharmacol. 2026 Mar 6;1019:178715. doi: 10.1016/j.ejphar.2026.178715. Online ahead of print.
ABSTRACT
L-theanine (Thea), a non-protein amino acid derived from Camellia sinensis (green tea) has emerged as a promising nutraceutical for the prevention and treatment of cardiovascular diseases (CVDs) and their comorbidities, thanks to its favorable safety profile, oral bioavailability, and natural origin. While extensive literature exists on green tea polyphenols, this review provides the first comprehensive synthesis of Thea's protective functions in specific cardiovascular contexts: attenuation of myocardial ischemia/reperfusion injury and heart failure, reduction of blood pressure, improvement of the lipid profile, inhibition of atherosclerotic plaque formation, promotion of adipose tissue browning, and modulation of glucose metabolism. This review also details the current evidence on Thea's cardioprotective mechanisms, with particular attention to its modulation of oxidative stress, inflammation, and apoptosis. We examined its regulatory effects on key molecular targets, including transcription factors such as Nrf2, PPARα, PPARγ, and NF-κB, as well as proteins involve in mitochondrial integrity (BCL-2, BAX), and metabolic homeostasis (AMPK, SREBP-1c, eNOS). Furthermore, this review advances the field by integrating pharmacokinetic data, safety assessments, recent advances in delivery systems, such as nanoencapsulation and co-formulation strategies, and connects mechanistic insights from preclinical models with potential clinical applications. We also identify critical gaps in research, such as the need for studies in chronic disease models, dose optimization, and evaluation in complex conditions like hypertrophic and dilated cardiomyopathy. Given the growing preclinical evidence and pending clinical validation, Thea represents a natural and compelling candidate for comprehensive cardiovascular prevention and treatment strategies.
PMID:41796839 | DOI:10.1016/j.ejphar.2026.178715