More than just caffeine: psychopharmacology of methylxanthine interactions with plant-derived phytochemicals

Schuster, Julius; Mitchell, Ellen Siobhan

doi:10.1016/j.pnpbp.2018.09.005

Cited by 43 publications

(25 citation statements)

References 81 publications

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“…Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem responsible for processing motor and sensory information, functioning in the CNS similarly to, and simultaneously with GABA [57,58]. In addition to the anxiolytic effects normally attributed to inhibitory neurotransmitters, glycine also induces the release of dopamine (DA) [59], which may explain at least part of the reported mood-enhancing effects of L-theanine [60]. In the pathway described above, L-theanine acts on AMPA receptors, causing the release of glycine, which subsequently acts on glycine receptors, triggering the release dopamine.…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

“…Unno et al [41] elucidated the importance of low relative caffeine content in mediating the ability of tea consumption to improve sleep and reduce bodily systemic responses to everyday stress. It is worthwhile to note, however, that, although caffeine may reduce anti-stress effects of tea, some studies show that certain tea compounds, such as polyphenols, theobromine and L-theanine, can enhance mood and cognitive effects of caffeine and alleviate negative psychophysiological effects of caffeine [60], which may confer added benefits to university students, among whom 92% reported to have consumed caffeine in the past year in a geographically-dispersed sample of United States university students [69].…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

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Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption

2019

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This article is a comprehensive review of the literature pertaining to the antidepressant effects and mechanisms of regular tea consumption. Meta-data supplemented with recent observational studies were first analyzed to assess the association between tea consumption and depression risk. The literature reported risk ratios (RR) were 0.69 with 95% confidence intervals of 0.62–0.77. Next, we thoroughly reviewed human trials, mouse models, and in vitro experiments to determine the predominant mechanisms underlying the observed linear relationship between tea consumption and reduced risk of depression. Current theories on the neurobiology of depression were utilized to map tea-mediated mechanisms of antidepressant activity onto an integrated framework of depression pathology. The major nodes within the network framework of depression included hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, inflammation, weakened monoaminergic systems, reduced neurogenesis/neuroplasticity, and poor microbiome diversity affecting the gut–brain axis. We detailed how each node has subsystems within them, including signaling pathways, specific target proteins, or transporters that interface with compounds in tea, mediating their antidepressant effects. A major pathway was found to be the ERK/CREB/BDNF signaling pathway, up-regulated by a number of compounds in tea including teasaponin, L-theanine, EGCG and combinations of tea catechins and their metabolites. Black tea theaflavins and EGCG are potent anti-inflammatory agents via down-regulation of NF-κB signaling. Multiple compounds in tea are effective modulators of dopaminergic activity and the gut–brain axis. Taken together, our findings show that constituents found in all major tea types, predominantly L-theanine, polyphenols and polyphenol metabolites, are capable of functioning through multiple pathways simultaneously to collectively reduce the risk of depression.

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Section: Mechanistic Considerationsmentioning

confidence: 99%

Section: Mechanistic Considerationsmentioning

confidence: 99%

Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption

2019

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“…Several authors (Dueñas et al, 2016;Innerhofer and Bernhardt, 2011;Patiño, 1968;Wise and Santander, 2018) reported the history and traditional use of I. guayusa leaves as a beverage used in ritual ceremonies in the northwest Amazon region. Three recent critical review article (Gan et al, 2018;Schuster and Mitchell, 2019;Wise and Negrin, 2019), focus the phytochemical composition, the bioactivity and the nutritional content of the I. guayusa leave extracts in order to empathize the history of safe traditional use of the species.…”

Section: Introductionmentioning

confidence: 99%

Optimisation of ultrasound-assisted extraction of phenolic antioxidants from Ilex guayusa Loes. leaves using response surface methodology

Crespo

Radice

Sánchez

et al. 2020

Heliyon

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The present study carried out the optimisation of the total polyphenol content (TPC) extraction assisted by ultrasound in Ilex guayusa leaves applying response surface methodology (RSM). Also, the evaluation of the antioxidant activity of the extract obtained under the optimal extraction conditions was performed. The effect of the variables like, time of sonication, temperature, ethanol/water ratio and solid/liquid relationship and the interactions between them were analysed through the use of a factorial design 2^4. The significant factors were considered for the optimisation, employing a Box-Behnken Design, and the TPC as response variables. It was found that a quadratic model was adequate, with an adjusted R 2 value of 0.9367. The optimal conditions proposed, by the response surface model were: an extraction temperature of 60 C, sonication time of 29.9 min and ethanol/water ratio of 76.8/23.2. The optimised leaves extract of I. guayusa show a TPC of 3.46 (AE0.17) g gallic acid equivalents/100 g d.w. Radical scavenger activity of the obtained extract at optimum conditions, was performed through the FRAP and ABTS methods, given as result: 0.080 mmol TROLOX equivalents/100 g d.w. and 40.71 μmol TROLOX equivalents/g d.w., respectively. Due to the present findings, I. guayusa extracts can be proposed as a promising component for functional beverages, cosmetic and pharmaceutical formulation.

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“…Methylxanthines are phytochemicals found at high concentrations in tea, coffee, and chocolate. Among them, theophylline, theobromine, and caffeine are the best known and are often described as mild psychostimulants [1][2][3]. In fact, caffeine is used daily as a somnolytic by millions of consumers, and as a result, methylxanthines are among the most widely consumed natural medicines, alongside polyphenols, alkaloids, and terpenes.…”

Section: Introductionmentioning

confidence: 99%

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

et al. 2020

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Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.

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More than just caffeine: psychopharmacology of methylxanthine interactions with plant-derived phytochemicals

Cited by 43 publications

References 81 publications

Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption

Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption

Optimisation of ultrasound-assisted extraction of phenolic antioxidants from Ilex guayusa Loes. leaves using response surface methodology

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

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