A pair of common phenolic compounds that turn up everywhere from cosmetics to pharmaceutical synthesis have now been put head to head in a laboratory model of allergic asthma, and only one of them delivered. The findings, drawn from a murine model of ovalbumin-induced allergic asthma in Balb/c mice, show how two structurally related molecules produced divergent immunological outcomes in this model.
The research team, whose author list includes Masoud Hassanzadeh Makoui as first author and Seyyed Shamsadin Athari as last author, set out to address a gap that has persisted despite the industrial ubiquity of both compounds. Hydroxybenzoic acids, which consist of a benzene ring bearing one or more hydroxyl groups, are widely used as preservatives in food and cosmetics, as intermediates in pharmaceutical synthesis, and as ingredients in skincare products prized for their anti-inflammatory and exfoliating properties. Salicylic acid, the 2-hydroxy form of the molecule, is perhaps the best known member of the family. Peroxybenzoic acid, by contrast, is a powerful oxidizing agent whose reactive peroxy group allows it to transfer oxygen atoms to other molecules, making it a workhorse for converting alkenes into epoxides in the synthesis of pharmaceuticals, natural products and fine chemicals. Yet, as the authors note, little has been known about the impact of either compound on the immune system or on allergic asthma specifically.
To probe that question, the investigators randomly divided forty female Balb/c mice, aged six to eight weeks, into four groups of ten. Three of the groups were sensitized to chicken ovalbumin through intraperitoneal injections on days 1 and 14, each containing 20 micrograms of ovalbumin mixed with 50 microliters of alum adjuvant. Aerosol challenges with a 1 percent ovalbumin solution followed on days 24, 26, 28 and 30, delivered by ultrasonic nebulization. One group of asthmatic mice then inhaled a 1 percent peroxybenzoic acid aerosol on days 25, 27 and 29, while another asthmatic group inhaled a 1 percent hydroxybenzoic acid aerosol under identical conditions on the same days. A fourth group of healthy mice served as controls. All animals were euthanized on day 31, and serum, bronchoalveolar lavage fluid and lung tissue were collected for analysis.
The histological work focused on two standard staining techniques. Lung sections were cut at 3 micrometers and stained with hematoxylin and eosin to visualize inflammatory cells, and with periodic acid Schiff to reveal mucus production and goblet cell hyperplasia. Two pathologists who were blinded to group assignment scored mucus production across ten randomly chosen microscopic fields per slide. The results were striking for one compound and unremarkable for the other. In mice treated with hydroxybenzoic acid, the peribronchial inflammation score fell by 36 percent, from 3.6 plus or minus 0.3 in untreated asthmatic animals to 2.3 plus or minus 0.1, a difference the authors report as statistically significant at p less than 0.05. Perivascular inflammation dropped even more dramatically, by 68 percent, from 3.8 plus or minus 0.1 to 1.2 plus or minus 0.2, significant at p less than 0.01.
Not every measure responded to the treatment, however. Mucus hypersecretion, scored at 3.9 plus or minus 0.1 in treated mice versus 3.8 plus or minus 0.2 in untreated asthmatic controls, showed no significant difference, with a p value of 0.45. Goblet cell hyperplasia was similarly unchanged, at 3.7 plus or minus 0.3 versus 3.7 plus or minus 0.2, with a p value of 0.88. Peroxybenzoic acid, meanwhile, failed to move any histopathological parameter at all, with all comparisons yielding p values above 0.05. The authors also report that neither compound produced noticeable adverse effects at the doses studied: the animals maintained normal activity levels, gained weight consistently, and showed no significant organ abnormalities during necropsy.
The immunological readouts told a complementary story. Asthmatic mice displayed marked elevations of the Th2 cytokines IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared with healthy controls, consistent with the type I hypersensitivity model driven by Th2 cells described in the study. Total IgE, the antibody hallmark of allergic sensitization, reached 1,000 plus or minus 100 nanograms per milliliter in asthmatic animals compared with just 5 plus or minus 2 in controls, a difference significant at p less than 0.001.
What explains the divergence between two molecules that share the same benzene ring? The authors argue that the ring itself is not the obstacle, and that the substituents attached to it determine biological behavior. Hydroxybenzoic acid carries a hydroxyl group on the ring, which they suggest is probably responsible for its anti-inflammatory properties, and they note that as a precursor to salicylate it may enhance the established anti-inflammatory mechanisms of aspirin through the inhibition of prostanoids. Peroxybenzoic acid, on the other hand, bears a peroxy group that confers pro-oxidant properties, which the authors suggest may diminish its therapeutic potential. The discussion also situates the findings in a wider literature: a methoxylated hydroxybenzoic acid derivative, 3,5-dimethoxy-4-hydroxybenzoic acid, has previously been shown to dose-dependently suppress ovalbumin-induced inflammation, lending support to the idea that this chemical family can modulate allergic responses.
The picture is not without complications. Aspirin, a close chemical relative through its salicylate core, has been reported to activate eosinophils in some contexts, which differs from the IL-5 and eosinophil suppression the authors observed for hydroxybenzoic acid in this study. The authors attribute the discrepancy to the unique acetyl group in aspirin or to dose-dependent effects that may produce opposing responses in different asthmatic subgroups. They also point to documented respiratory reactions associated with benzoate in aspirin-allergic patients, and they contrast this with their data from a murine asthma model, a distinction that highlights the need to stratify patients by endotype, separating aspirin-exacerbated respiratory disease from non-AERD phenotypes, and the fact that bioactivity can vary significantly even among structurally similar compounds.
The authors are candid about the limits of what this mouse study can establish. The sample was small and drawn from a single center, which constrains statistical power and generalizability, and they call for larger, multi-center trials to validate efficacy and safety. The precise molecular mechanisms by which hydroxybenzoic acid exerts its anti-inflammatory action remain unclear, requiring detailed in vitro and molecular pathway analyses. The study focused primarily on IL-5 and eosinophilic inflammation without assessing other critical asthma mediators such as leukotrienes or airway hyperresponsiveness, so broader immunophenotyping and functional airway studies are needed. Future clinical work, they argue, should stratify patients by aspirin sensitivity, eosinophilic endotype and relevant genetic polymorphisms to identify the subgroups most likely to benefit while minimizing adverse reactions.
Subject of Research: Effects of hydroxybenzoic acid and peroxybenzoic acid on airway inflammation and Th2 cytokines in a murine model of allergic asthma
Article Title: Effect of peroxybenzoic acid and hydroxybenzoic acid on allergic asthma
Article References: Hassanzadeh Makoui, M., Koushki, M., Amiri-Dashatan, N., Khaleghi Khorrami, A., Biglari, F., Borji, M., & Athari, S. S. (2025). Effect of peroxybenzoic acid and hydroxybenzoic acid on allergic asthma. BMC Biomedical Engineering, 7(1), Article 13. https://doi.org/10.1186/s42490-025-00099-z
Image Credits: AI Generated
DOI: 10.1186/s42490-025-00099-z
Keywords: allergic asthma, hydroxybenzoic acid, peroxybenzoic acid, IL-5, eosinophils, Balb/c mice, ovalbumin model, Th2 cytokines, IgE, airway inflammation, histopathology, preclinical study
News Source: Gregory Coleman. (November 6, 2026). Research report: Effect of peroxybenzoic acid and hydroxybenzoic acid on allergic asthma. Scienmag.
