4-hydroxybenzoic acid

Overview

4-Hydroxybenzoic acid (4-HBA; p-hydroxybenzoic acid) is a phenolic benzoic acid derivative characterized by a hydroxyl group in the para position relative to the carboxylic acid. It occurs naturally in a range of plant-derived matrices and is frequently detected in phytochemical profiling studies alongside related phenolics such as ferulic acid, syringic acid, and 3,4-dihydroxybenzoic acid. In biomedical and analytical contexts, 4-hydroxybenzoic acid is of interest both as a bioactive plant metabolite and as a measurable small molecule in biological and food samples.

Recent research has also highlighted 4-hydroxybenzoic acid as a molecule with translational relevance. It has been investigated as a biosynthetic precursor in coenzyme Q (CoQ) metabolism, particularly in the setting of COQ2 deficiency, where substrate supplementation may help restore endogenous CoQ10 production. In parallel, it has been explored as a potential disease-associated biomarker, including work on non-invasive detection of gastric cancer-associated 4-HBA. These studies place 4-hydroxybenzoic acid at the intersection of natural products chemistry, metabolic disease, and biomarker research.

Focus of Latest Publications

Several recent studies used 4-hydroxybenzoic acid as an analytically detected phytochemical in plant extracts. In Salvia heldreichiana, HPLC analysis identified 4-hydroxybenzoic acid, rosmarinic acid, p-coumaric acid, and chrysin as major bioactive constituents. This work linked the compound to a broader phytochemical profile examined in the framework of antioxidant activity, enzyme inhibition, molecular docking studies, and CAVER tunnel analysis. Similarly, in rice straw lignocellulosic residues, LC-ESI/LTQ-Orbitrap-HRMS/MS profiling identified 4-hydroxybenzoic acid as one of the major phenolic contributors after microwave-assisted extraction. In lentil hulls, UHPLC-QTOF-MS/MS analysis detected p-hydroxybenzoic acid among phenolic compounds distributed across free, esterified, glycosylated, and insoluble-bound fractions after steam explosion pretreatment. These studies reinforce its common occurrence in plant phenolic fractions and its relevance in extraction and profiling workflows.

Beyond phytochemistry, 4-hydroxybenzoic acid has been studied as a metabolic therapeutic candidate. In preclinical and first-in-human evidence for mitochondrial COQ2 deficiency, 4-hydroxybenzoic acid was described as a biosynthetic precursor of CoQ and a substrate enhancement treatment for pathogenic COQ2 variants. The study reported that patient-derived fibroblasts treated in vitro with 4-HBA showed a marked increase in endogenous CoQ10 levels, supporting its potential to bypass impaired CoQ biosynthesis. The authors concluded that 4-HBA is a promising targeted metabolic treatment for COQ2-related CoQ deficiency and emphasized the need for further clinical investigation.

The compound has also been investigated in diagnostic and analytical applications. A ZIF/CDs-based fluorescent sensor was developed for the selective and sensitive detection of 4-hydroxybenzoic acid, described in that study as a potential gastric cancer biomarker. This indicates interest in 4-HBA not only as a metabolite but also as a measurable marker in disease-related sample analysis.

Additional studies contextualized 4-hydroxybenzoic acid among phenolic inhibitors and chromatographic analytes. In Candida boidinii XM02G, resistance testing included phenolic inhibitors such as benzoic acid, syringic acid, p-hydroxybenzoic acid, and ferulic acid, reflecting the compound’s relevance in microbial tolerance studies. In chromatographic research using a temperature-responsive ionic liquid hydrogel coating on silica, the retention behavior of both benzoic acid and 4-hydroxybenzoic acid was examined, and the retention factor did not follow the Van’t Hoff equation. Together, these studies show that 4-hydroxybenzoic acid is used as a reference analyte in separation science, a phenolic compound in plant chemistry, and a biologically relevant substrate or biomarker in translational research.

Key Publications

• Jun Exploring the biotechnological potential of Candida boidinii XM02G: High xylitol production efficiency and high tolerance to inhibitory compounds. (Fungal biology, 2026, PMID 42191238): "The yeast's resistance was tested against phenolic inhibitors: benzoic acid, syringic acid, p-hydroxybenzoic acid, and ferulic acid."
• Jun Evaluation of the Phytochemical Composition, Antioxidant Activity, and Enzyme Inhibitory Potential of Salvia heldreichiana Within the Framework of Molecular Docking and CAVER Tunnel Analysis. (ChemistryOpen, 2026, PMID 42220228): "HPLC analysis identified 4-hydroxybenzoic acid, rosmarinic acid, p-coumaric acid, and chrysin as the major bioactive constituents."
• May Temperature-responsive ionic liquid hydrogel coating silica used for multi-mode chromatographic stationary phase. (Journal of chromatography. A, 2026, PMID 41865735): "It was noteworthy that the retention factor (k) for both benzoic acid and 4-hydroxybenzoic acid didn't adhere to the Van't Hoff equation."
• May Green optimisation of microwave-assisted extraction of phenolic compounds from rice straw lignocellulosic residues and LC-HRMS-based cultivar profiling. (Food chemistry, 2026, PMID 41825384): "LC-ESI/LTQ-Orbitrap-HRMS/MS enabled detailed profiling of phenolic compounds, with 4-hydroxybenzoic acid and quercetin-3-glucoside as major contributors."
• May Non-invasive detection of gastric cancer biomarker 4-HBA via a ZIF/CDs-based fluorescent sensor. (Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 2026, PMID 41650924): "...for the selective and sensitive detection of 4-hydroxybenzoic acid (4-HBA), a potential gastric cancer biomarker."
• May Preclinical and first-in-human evidence of 4-hydroxybenzoic acid for mitochondrial COQ2 deficiency. (Brain : a journal of neurology, 2026, PMID 40929079): "These findings support 4-HBA as a promising targeted metabolic treatment for COQ2-related CoQ deficiency and highlight the need for further clinical investigation."
• May Sustainable valorization of Eston lentil hulls: steam explosion as a green technology to enhance the phenolic compounds release and their potential health benefits. (Food chemistry, 2026, PMID 41762877): "UHPLC-QTOF-MS/MS analysis identified 21 phenolic compounds, including catechin, protocatechuic acid, and p-hydroxybenzoic acid, across free, esterified, glycosylated, and insoluble-bound fractions."