Health benefits of methylxanthines in neurodegenerative diseases

Oñatibia-Astibia, Ainhoa; Franco, Rafael; Martínez‐Pinilla, Eva

doi:10.1002/mnfr.201600670

Cited by 70 publications

(49 citation statements)

References 140 publications

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“…In humans, the plasma concentration of theobromine has been reported to be as high as 63 µM following the consumption of chocolate (Oñatibia‐Astibia et al, ). The relationship between Ki and inhibitor concentration for a noncompetitive inhibitor is given by equation 1:

V m a x a p p = \frac{Vmax}{1 + \frac{I}{Ki}}

…”

Section: Discussionmentioning

confidence: 99%

“…The longer half-life of theobromine may mean its effects will be more prolonged than those of caffeine. It is also important to note that theobromine may be formed from caffeine breakdown in vivo (Oñatibia-Astibia, Franco, & Martínez-Pinilla, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Oñatibia-Astibia et al, 2017). The relationship between Ki and inhibitor concentration for a noncompetitive inhibitor is given byequation 1: Equation 1.…”

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confidence: 99%

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Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

Shanahan¹,

O'Sullivan

Tipton

et al. 2018

J Food Biochem

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Methylxanthines are among the most widely consumed drugs in the world and evidence of their health benefits has been growing in recent years. Primary Amine Oxidase (PrAO) has been recognized as a therapeutic target for the amelioration of inflammatory, vascular, and neurodegenerative diseases. Previous work in our laboratories showed that caffeine inhibited Bovine PrAO with a Ki of 1.0 mM using benzylamine as substrate. This study aimed to extend our previous work and explore the possibility that related methylxanthines might influence PrAO activity. While paraxanthine, theophylline, and 7‐methylxanthine had little effect on PrAO, theobromine was a noncompetitive inhibitor with a Ki of 276 ± 44 µM. The specific structural elements of methylxanthines that are required for inhibition allow us to suggest that their binding site on PrAO may be a target for therapeutics. The health benefits associated with dietary methylxanthine consumption could involve PrAO inhibition. Practical applications Inhibition of PrAO by methylxanthines may be significant in conferring health benefits. The design of PrAO inhibitors based on the structural motifs identified in this study (N‐methylation at specific locations) is indicated. Existing therapeutics based on a core xanthine structure can be evaluated for their effects on PrAO. PrAO inhibition must be considered as a potential mediator of the beneficial health effects of some methylxanthines. If inhibition in human tissues is comparable to, or greater than, that found in these studies it points to an important role for these compounds in human health.

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V m a x a p p = \frac{Vmax}{1 + \frac{I}{Ki}}

…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

Shanahan¹,

O'Sullivan

Tipton

et al. 2018

J Food Biochem

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“…One of the hypothesis behind the benefits of sustained methylxanthine intake for the CNS, also backed up by the fact that virtually all societies have methylxanthinecontaining beverages, is that active neurons are less prone to death. Adenosine receptor antagonism produces neuronal activation and, eventually, active neurons have more tools to cope with environmental factors leading to oxidative stress (Franco et al, 2013;Oñatibia-Astibia et al, 2017).…”

Section: Caffeine and Other Methylxanthinesmentioning

confidence: 99%

Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson’s Disease

Franco

Rivas‐Santisteban

Reyes‐Resina

et al. 2020

Front. Aging Neurosci.

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The exact cause of Parkinson's disease (PD), the second most prevalent neurodegenerative disease in modern societies, is still unknown. Many scientists point out that PD is caused by a complex interaction between different factors. Although the main risk factor is age, there are other influences, genetic and environmental, that individually or in combination may trigger neurodegenerative changes leading to PD. Nowadays, research remains focused on better understanding which environmental factors are related to the risk of developing PD and why. In line with the knowledge on evidence on exposures that prevent/delay PD onset or that impact on disease progression, the aims of this review were: (i) to comment on the non-genetic risk factors that mainly affect idiopathic PD; and (ii) to comment on seemingly reliable preventive interventions. We discuss both environmental factors that may affect the central nervous system (CNS) or the intestinal tract, and the likely mechanisms underlying noxious or protective actions. Knowledge on risk, protective factors, and mechanisms may help to envisage why nigral dopaminergic neurons are so vulnerable in PD and, eventually, to design new strategies for PD prevention and/or anti-PD therapy. This article reviews the variety of the known and suspected environmental factors, such as lifestyle, gut microbiota or pesticide exposition, and distinguishes between those that are harmful or beneficial for the PD acquisition or progression. In fact, the review covers one of the most novel players in the whole picture, and we address the role of microbiota on keeping a healthy CNS and/or on preventing the "side-effects" related to aging.

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“…stimulation of the central nervous system and gastric secretion, diuresis, bronchodilation, and stimulation of skeletal muscles in high doses . They also display health benefits in diseases involving cell death in the nervous system (Oñatibia Astibia, Franco, & Martínez Pinilla, 2017).…”

Section: Introductionmentioning

confidence: 99%

Application of Infrared Spectroscopy and Chemometrics to the Cocoa Industry for Fast Composition Analysis and Fraud Detection

Vásconez¹

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Resum amb un contingut de pellofa inferior al 5% (considerat el límit de acceptació en pols de cacau pel Codex Alimentarius) i continguts de pellofa entre 5 i 40%. A l'estudi d'adulteració de cacau en pols amb farina de garrofa, el 100% de les mostres es classifiquen correctament en tres grups: cacau, farina de garrofa i mescles. En ambdós estudis, s'ha pogut calcular el percentatge d'adulterant o material no desitjat present a les mostres mitjançant la construcció de models de regressió PLS. En relació amb la pellofa de cacau, el millor model de predicció PLS s'ha obtingut amb 1 variable latent (LV), amb R 2 de 0,975 i 0,967, i un error quadràtic medi d'1,91 i 2,43%, per als conjunts de calibratge i validació externa, respectivament. Per a l'estudi d'adulteració amb farina de garrofa, el model de regressió PLS s'obté amb una variable latent (LV) amb un R 2 de 0.980 i 0.974, i un error correcte mitjà de 2,9 i 3,2% per als conjunts de calibració i validació externa, respectivament.En el segon capítol, l'anàlisi composicional del cacau en pols s'orientà al control dels canvis produïts en el contingut de flavanols i metilxantines a causa del procés d'alcalinització al que se sotmet el cacau en pols. Es va determinar el contingut de catequina, epicatequina, cafeïna i teobromina mitjançant cromatografia líquida d'alta resolució (HPLC), i es van correlacionar els continguts obtinguts per a cadascun d'estos composts amb les determinacions NIR. Es van obtindré bons models per a la predicció dels composts mitjançant regressió PLS amb valors superiors a 3 per a la relació entre el rendiment i la desviació (RDP), la qual cosa demostra que els models obtinguts poden ser emprats per a la ràpida i fiable predicció del contingut de flavanols i metilxantines en cacaus naturals o amb diferents nivells d'alcalinització. Abstract AbstractCocoa is a product of high value, not only because of its sensory characteristics, but also because it has a high content of antioxidants and stimulating alkaloids with health effects. Due to the high demand, the cocoa powder industry has the challenge of ensuring the quality of large volumes of production in a fast and accurate way, avoiding the presence of contaminants or adulterants in the raw material, offering products where the healthy properties are preserved. The near infrared spectroscopy (NIR) is a rapid and non-destructive technology useful in the analysis of food products. The present doctoral thesis focuses on evaluating the potential use of NIR as a quality control tool in order to solve problems that arise in the cocoa industry powdered. The problems to solve include the detection of unwanted materials or adulterants in the cocoa powder, and the rapid and accurate monitorization of the flavanols and methylxanthines content in the cocoa powder during the alkalization process. The first chapter evaluates the viability of the NIR, in combination with chemometric analysis, in the detection of presence of unwanted materials or adulterants such as cocoa shell or carob flour. For this, diff...

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Health benefits of methylxanthines in neurodegenerative diseases

Cited by 70 publications

References 140 publications

Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson’s Disease

Application of Infrared Spectroscopy and Chemometrics to the Cocoa Industry for Fast Composition Analysis and Fraud Detection

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