Comparative Metabolomics Reveals L-Theanine as a Candidate Contributor to Cultivar-Specific Differences in PTZ-Induced Hyperactivity in Zebrafish

Foods. 2026 Nov 7;15(21):3992. doi: 10.3390/foods15213992.

ABSTRACT

Hyperactivity and excessive neuronal excitation may lead to sleep disturbances and affect neurological health and overall quality of life, highlighting the need for safe, natural remedies. L-theanine, a natural bioactive compound in tea, has attracted interest for its potential effects on behavioral activity, although its effects on PTZ-induced locomotor responses in zebrafish remain unclear. Given the substantial variation in L-theanine accumulation among tea cultivars, we compared the metabolomic profiles of Camellia sinensis cultivars ‘Baiye 1’ (BY) and ‘Longjing 43’ (LJ43) and found that BY accumulated higher levels of L-theanine than LJ43. BY tea infusion exhibited stronger effects on pentylenetetrazole (PTZ)-induced hyperactivity in zebrafish, while LJ43 showed limited efficacy. Administering exogenous L-theanine, either alone or in combination with GABA or melatonin, alleviated hyperactivity and partially modulated the expression of gabra1 and mtnr1aa in zebrafish. Molecular docking revealed putative structural interactions of L-theanine with both GABRA1 and MTNR1AA, suggesting that GABA- and melatonin-related receptors may be involved in its attenuation of PTZ-induced hyperactivity. These findings highlight L-theanine as a potential contributor to the attenuation of PTZ-induced hyperactivity. Considering the complex composition of tea infusions, the distinct behavioral responses between BY and LJ43 may reflect the combined effects of multiple bioactive constituents, among which L-theanine may be one plausible contributor.

PMID:43027623 | DOI:10.3390/foods15213992