Antidepressant-like effects of dietary gardenia blue pigment derived from genipin and tyrosine

• Published in: Food & function Vol. 1; no. 8; pp. 4533 - 4545
• Main Authors: Li, Kuang-Dai, Yan, Kuo, Wang, Qiang-Song, Tian, Jun-Sheng, Xu, Dong, Zhang, Wen-Yan, Cui, Yuan-Lu
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01.08.2019
• Subjects: Adrenal glands; Adrenocorticotropic hormone; Amino acids; Animal behavior; Animal models; Animals; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - chemistry; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Corpus striatum; Corticosterone; Corticosterone - metabolism; Corticotropin-releasing hormone; Depression - drug therapy; Depression - genetics; Depression - metabolism; Depression - psychology; Diet; Dopamine; Food dyes; Gardenia - chemistry; Gardens & gardening; Genipin; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Iridoids - chemistry; Lipopolysaccharides; Male; Metabolomics; Mice; Mice, Inbred C57BL; Mitochondria; Monoamines; Neostriatum; Neurotransmitter release; Neurotransmitters; Norepinephrine; Oxidative metabolism; Pigments; Pigments, Biological - administration & dosage; Pigments, Biological - chemistry; Pituitary; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - metabolism; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Rats; Rats, Sprague-Dawley; Restoration; Serotonin; Serotonin - metabolism; Structural integrity; Testosterone; Tumor necrosis factor-α; Tyrosine; Tyrosine - chemistry
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo00480g

Gardenia blue pigments derived from genipin reacting with amino acids have been used as natural food colorants for nearly 30 years in East Asia. However, their pharmacological effects, especially antidepressant-like effects, have not been reported so far. In this study, one of the gardenia blue pigments, was obtained from the reaction of genipin with tyrosine (genipin-tyrosine derivant (GTD)), and its antidepressant-like effects were investigated in lipopolysaccharide (LPS) or chronic unpredictable mild stress (CUMS) models. The results showed that GTD could attenuate depressive-like behaviors in both animal models. GTD reversed the LPS-induced cytokine increase of TNF-α, IL-6, and corticosterone (CORT) in mice plasma and hippocampus. In CUMS rats, GTD treatment significantly reduced hypothalamic-pituitary-adrenal (HPA) axis-related stress hormone levels in plasma including those of CORT, adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH). Besides, GTD increased plasma testosterone and hippocampal brain-derived neurotrophic factor (BDNF) levels in CUMS rats. GTD increased serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in rat hippocampus and corpus striatum. Consistently, hippocampal metabolomic analysis demonstrated that GTD restored monoamine neurotransmitter metabolism, mitochondrial oxidative function, and membrane structural integrity. Our data suggested that GTD produced antidepressant-like activity through the restoration of the HPA axis hormone balance and the regulation of neurotransmitter release. Gardenia blue pigments derived from genipin reacting with amino acids have antidepressant effect.