Whole grain metabolite 3,5-dihydroxybenzoic acid is a beneficial nutritional molecule with the feature of a double-edged sword in human health: a critical review and dietary considerations

Wagner, Waldemar; Sobierajska, Katarzyna; Pułaski, Łukasz; Stasiak, Anna

doi:10.1080/10408398.2023.2203762

Critical Reviews in Food Science and Nutrition

2023

DOI: 10.1080/10408398.2023.2203762

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Whole grain metabolite 3,5-dihydroxybenzoic acid is a beneficial nutritional molecule with the feature of a double-edged sword in human health: a critical review and dietary considerations

Waldemar Wagner

Katarzyna Sobierajska

Łukasz Pułaski

et al.

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Cited by 2 publications

References 152 publications

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Alkylresorcinols trap malondialdehyde in whole grain crackers

Alcon,

Hidalgo,

Zamora

2025

Food Chemistry

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Alkylresorcinols trap malondialdehyde in whole grain crackers

Alcon,

Hidalgo,

Zamora

2025

Food Chemistry

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Orthosteric and allosteric modulation of human HCAR2 signaling complex

Mao,

Gao,

Zang

et al. 2023

Nat Commun

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Hydroxycarboxylic acids are crucial metabolic intermediates involved in various physiological and pathological processes, some of which are recognized by specific hydroxycarboxylic acid receptors (HCARs). HCAR2 is one such receptor, activated by endogenous β-hydroxybutyrate (3-HB) and butyrate, and is the target for Niacin. Interest in HCAR2 has been driven by its potential as a therapeutic target in cardiovascular and neuroinflammatory diseases. However, the limited understanding of how ligands bind to this receptor has hindered the development of alternative drugs able to avoid the common flushing side-effects associated with Niacin therapy. Here, we present three high-resolution structures of HCAR2-Gi1 complexes bound to four different ligands, one potent synthetic agonist (MK-6892) bound alone, and the two structures bound to the allosteric agonist compound 9n in conjunction with either the endogenous ligand 3-HB or niacin. These structures coupled with our functional and computational analyses further our understanding of ligand recognition, allosteric modulation, and activation of HCAR2 and pave the way for the development of high-efficiency drugs with reduced side-effects.

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Whole grain metabolite 3,5-dihydroxybenzoic acid is a beneficial nutritional molecule with the feature of a double-edged sword in human health: a critical review and dietary considerations

Cited by 2 publications

References 152 publications

Alkylresorcinols trap malondialdehyde in whole grain crackers

Alkylresorcinols trap malondialdehyde in whole grain crackers

Orthosteric and allosteric modulation of human HCAR2 signaling complex

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