L-theanine as a multifunctional neuroprotective and cardiomodulatory agent: Hydroxyl radical scavenging, neurotransmitter modulation, and attenuation of stress-induced cardiac responses

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Oxidative stress, resulting from excessive free radical production, plays a pivotal role in the pathogenesis of neurodegenerative and cardiovascular disorders. L-theanine, a unique non-protein amino acid present in tea (Camellia sinensis), is recognized for its antioxidant, neuroprotective, and anxiolytic properties; however, its direct hydroxyl radical scavenging activity and effects on neurochemical pathways and cardiovascular responses remain inadequately understood. The present study evaluated the in vitro hydroxyl radical (•OH) scavenging capacity of L-theanine and investigated its effects on dopaminergic and cholinergic neurotransmission, as well as stress-induced cardiac chronotropic responses in Swiss albino mice. Hydroxyl radicals were generated using a ferrous–ascorbate–EDTA system in the presence of L-theanine or reference antioxidants (catalase, melatonin, and glutathione), and the hydroxyl radical adducts, 2,3- and 2,5-dihydroxybenzoic acid, were quantified using high-performance liquid chromatography. Mice received intraperitoneal L-theanine (5 mg/kg) twice daily for seven days. Striatal dopamine levels and hippocampal acetylcholinesterase activity were subsequently determined, while heart rate was measured non-invasively using a MouseSTAT® Jr. pulse oximeter under acute stress conditions. L-theanine significantly inhibited hydroxyl radical formation, with greater scavenging activity than glutathione at 0.075 mM. The treatment also significantly increased striatal dopamine levels and reduced hippocampal acetylcholinesterase activity, indicating enhanced dopaminergic neurotransmission and modulation of cholinergic signaling. In addition, L-theanine attenuated the stress-induced increase in heart rate, demonstrating a negative chronotropic effect. These findings demonstrate that L-theanine possesses potent antioxidant, neuroprotective, and cardiomodulatory properties, supporting its potential as a multifunctional therapeutic candidate for oxidative stress-associated neurodegenerative and cardiovascular disorders.