# Antioxidant and neuromodulatory effect of gallic acid prevents anxiety-like symptoms of omeprazole

**Authors:** Noreen Samad, Natasha Manzoor, Shehreen Saleem, Saima Khaliq, Umer Ejaz, Mahwish Arshad, Sadaf Ahmad, Bakar Bin Khatab Abbasi, Ali Irfan, Yousef A. Bin Jardan

PMC · DOI: 10.1039/d5ra09924b · RSC Advances · 2026-02-17

## TL;DR

Gallic acid reduces anxiety and neurological issues caused by omeprazole in rats through antioxidant and neuromodulatory effects.

## Contribution

Gallic acid is shown to mitigate omeprazole-induced anxiety and oxidative stress in a rat model.

## Key findings

- Gallic acid improved locomotion and reduced anxiety-like behaviors in omeprazole-treated rats.
- Gallic acid decreased oxidative stress and normalized serotonin metabolism in the hippocampus.
- Gallic acid reduced 5-HT1A receptor expression in omeprazole-administered rats.

## Abstract

This research focuses on the protective impacts of gallic acid (GAL) on OMP-instigated anxiety. In this experiment, 48 male Sprague-Dawley rats were grouped into 6 (n = 8): (I) VEH + VEH (1 mL kg−1), (II) VEH + GAL [low dose; (50 mg kg−1)] (III) VEH + GAL [high dose; (100 mg kg−1)] (IV) VEH + OMP (20 mg kg−1), (V) GAL (low dose) + OMP V) GAL (high dose) + OMP. The animals were administered their corresponding drugs intraperitoneally (IP) for four weeks, once daily. Subsequently, during the treatment period, behavioral tests were performed, including open field activity (OFA) and home cage activity (HCA) to assess locomotion and elevated plus maze (EPM), and light-dark activity (LDA) for anxious-like symptoms, respectively. Following behavioral assessments, the rats were decapitated, and their hippocampus was removed. The hippocampus was utilized for biochemical, neurochemical, and histopathological examinations. The results revealed that OMP produced hypolocomotion, anxiety-like behavior, elevated oxidative-stress biomarkers and inflammatory-cytokines, and reduced the activity of antioxidant enzymes and serotonin metabolism. Administration of GAL (both doses) increased (p < 0.05) locomotor activity, reduced (p < 0.05) anxiety, decreased (p < 0.05) oxido-neuroinflammation, and normalized (p < 0.05) 5-HT metabolism and histopathological alteration, followed by OMP. 5-HT1A receptor analysis exhibited OMP-administration sensitized relative expression of 5-HT1A receptors, while GAL at both doses (p < 0.05) decreased 5-HT1A receptor expression in VEH and OMP-administered rats. It is proposed that GAL, as an antioxidant and neuromodulator, can be used for reducing OMP-induced hypolocomotion, anxiety, and associated neurological problems.

This research focuses on the protective impacts of gallic acid (GAL) on OMP-instigated anxiety.

## Linked entities

- **Chemicals:** gallic acid (PubChem CID 370), omeprazole (PubChem CID 4594)
- **Diseases:** anxiety (MONDO:0005618)

## Full-text entities

- **Genes:** Gal (galanin and GMAP prepropeptide) [NCBI Gene 29141] {aka Galn}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Actb (actin, beta) [NCBI Gene 81822] {aka Actx}, CAT [NCBI Gene 100541757], IL-6 [NCBI Gene 100548599], Omp (olfactory marker protein) [NCBI Gene 24612], Gast (gastrin) [NCBI Gene 25320] {aka Gas, PPG34}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Htr2c (5-hydroxytryptamine receptor 2C) [NCBI Gene 25187] {aka 5-HT2C, 5-HTR2C, 5HT-1C}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Gal (galanin and GMAP prepropeptide) [NCBI Gene 14419] {aka Galn}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Htr1a (5-hydroxytryptamine receptor 1A) [NCBI Gene 24473] {aka 5HT1A, RAT5HT1A}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}
- **Diseases:** anxious-like symptoms (MESH:D012816), anemia (MESH:D000740), ulcer (MESH:D014456), pathological abnormalities (MESH:D005598), depression (MESH:D003866), neuronal degeneration (MESH:D009410), anxiogenic drug (MESH:D000081015), OMP (MESH:C562589), cognitive adverse effects (MESH:D003072), gastric ECL hyperplasia (MESH:D006965), gastric reflux (MESH:D005764), gastric ulceration (MESH:D013276), neurodegeneration (MESH:D019636), Inflammatory (MESH:D007249), Anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), Behavioral deficits (MESH:D019958), diabetes (MESH:D003920), cancers (MESH:D009369), behavioral abnormalities (MESH:D001523), neurotoxicity (MESH:D020258), neurobehavioral disorders (MESH:D019954), anxiolytic effects (MESH:D065606), obese (MESH:D009765), weight gain (MESH:D015430), sedative (MESH:C535788), neurological problems (MESH:D009461)
- **Chemicals:** Hematoxylin (MESH:D006416), Disodium Hydrogen Phosphate (MESH:C018279), 5-HIAA (MESH:D006897), H2O2 (MESH:D006861), Sodium-Bicarbonate (MESH:D017693), Dithio-bis-nitrobenzoic acid (-), superoxide (MESH:D013481), MDA (MESH:D008315), TCA (MESH:D014238), tannins (MESH:D013634), Omeprazole (MESH:D009853), NBT (MESH:D009580), Hydroxylamine-Hydrochloride (MESH:D019811), Na2CO3 (MESH:C005686), chloroform (MESH:D002725), lipid (MESH:D008055), GSH (MESH:D005978), polyphenol (MESH:D059808), 5-HT (MESH:D012701), glucose (MESH:D005947), ellagic acid (MESH:D004610), TBARS (MESH:D017392), Eosin (MESH:D004801), acetate (MESH:D000085), dopamine (MESH:D004298), GA (MESH:D005708), oxygen (MESH:D010100), GAL (MESH:D005707), Phosphate (MESH:D010710), saline (MESH:D012965), fat (MESH:D005223), lipid peroxides (MESH:D008054), adrenaline (MESH:D004837), triglycerides (MESH:D014280), EDTA (MESH:D004492), TRIzol (MESH:C411644), Sodium-Azide (MESH:D019810), ellagitannins (MESH:D047348), water (MESH:D014867), digallic acid (MESH:C067648), ethanol (MESH:D000431), Acetic-Acid (MESH:D019342), Potassium-Dichromate (MESH:D011192), benzimidazole (MESH:C031000), noradrenaline (MESH:D009638)
- **Species:** Emblica officinalis (amla, species) [taxon 296036], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12910346/full.md

## References

74 references — full list in the complete paper: https://tomesphere.com/paper/PMC12910346/full.md

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Source: https://tomesphere.com/paper/PMC12910346