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Title
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Exploring the therapeutic potential of French maritime pine bark extract in attention-deficit hyperactivity disorder and arterial stiffness
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Author
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Abstract
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| Exploring the therapeutic potential of French Maritime Pine Bark Extract in Attention-Deficit Hyperactivity Disorder and Arterial Stiffness Non-communicable diseases (NCDs) including neurodevelopmental diseases such as Attention-Deficit Hyperactivity Disorder (ADHD) and cardiovascular diseases, represent a growing global health problem that impacts the quality of life. Polyphenols, found in dietary sources like fruits and vegetables, offer promising health benefits, notably antioxidant and anti-inflammatory properties, potentially alleviating NCD’s burden, associated with oxidative stress and inflammation. This PhD thesis explores a patented polyphenol-rich extract from the French Maritime Pine bark (PBE; Pinus pinaster) as a potential novel treatment option for NCDs due to its antioxidant and anti-inflammatory activities. Firstly, PBE assesses the role in ADHD, a prevalent neurodevelopmental disorder with implicated dopaminergic dysfunction and immune and oxidant-antioxidant imbalances. Since methylphenidate, the first-choice medication for ADHD, is linked to adverse effects, novel treatment options are highly warranted. A 10-week double-blind, randomised clinical trial compared PBE to placebo and methylphenidate, and revealed that both methylphenidate and PBE significantly improved hyperactivity/impulsivity, and proved that PBE is a good alternative for methylphenidate. Besides, loss of appetite, indicated by the neurochemical parameter neuropeptide Y, and weight loss were observed for methylphenidate, whereas a significant weight gain was established for PBE. Moreover, a potential prebiotic effect of PBE was explored by investigating its impact on the gut microbiota via amplicon sequencing of the full length 16s rRNA ribosomal subunit. Though no clear prebiotic effects were observed, subtle changes emerged. Secondly, PBE’s therapeutic potential in cardiovascular diseases, particularly arterial stiffness, was studied. Both oxidative stress and inflammation appear to play a role in arterial stiffness and can lead to structural and functional changes in the arterial wall, impair endothelial function, and thus promote the development of cardiovascular diseases. PBE was tested in an array of in vitro assays on oxidative and inflammatory mechanisms contributing to arterial stiffness and results showed PBE’s inhibition of cyclooxygenase enzymes and NF-κB activity and alterations in protein expression levels associated with pathways underlying arterial stiffness. Lastly, PBE was subjected to in vitro gastrointestinal biotransformation, which mimics the gastric, intestinal and colonic phase, including faecal fermentation in an anaerobic environment. Samples were taken at different timepoints and analysed with UHPLC-ESI-QTOF-MS. Extensive biotransformation of PBE was observed and various biotransformation products could be identified. To conclude, our study provides valuable insights into the complex interplay between polyphenols, biotransformation, and potential health benefits, contributing to the ongoing efforts to address the global burden of NCDs. |
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Language
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English
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Publication
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Antwerp
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Universiteit Antwerpen, Faculteit Farmaceutische, Biomedische en Diergeneeskundige Wetenschappen, Departement Farmaceutische Wetenschappen
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2024
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DOI
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10.63028/10067/2051630151162165141
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Volume/pages
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389 p.
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Note
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Hermans, N. [Supervisor]
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Pieters, L. [Supervisor]
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Full text (open access)
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