# Evaluation of Callistemon citrinus Compounds to Reduce Brain Oxidative Stress in Rats Fed High-Fat-Sucrose Diet

**Authors:** Aram Josué García-Calderón, Oliver Rafid Magaña-Rodríguez, Luis Alberto Ayala-Ruiz, José Armando Hernández-Soto, Jonathan Saúl Piñón-Simental, Luis Gerardo Ortega-Pérez, Asdrubal Aguilera-Méndez, Patricia Ríos-Chávez

PMC · DOI: 10.3390/metabo16010024 · 2025-12-25

## TL;DR

This study shows that compounds from Callistemon citrinus can reduce brain oxidative stress and inflammation in rats on a high-fat-sucrose diet.

## Contribution

Identifies specific bioactive compounds in Callistemon citrinus responsible for neuroprotective effects against diet-induced oxidative stress.

## Key findings

- Callistemon citrinus compounds modulated antioxidant enzymes and reduced oxidative biomarkers in rat brains.
- The compounds decreased pro-inflammatory enzyme activities despite a high-fat-sucrose diet.
- Both individual and mixed compounds showed neuroprotective effects against oxidative stress.

## Abstract

Background: The association between oxidative stress and inflammation in obesity motivates investigation of the effects of d-limonene, gallic acid, ellagic acid, p-coumaric acid, and their mixture, which are major compounds of Callistemon citrinus, on oxidative stress and inflammation in the brains of rats fed a high-fat-sucrose diet. This study aimed to identify the specific bioactive compounds in C. citrinus leaf extract responsible for its neuroprotective effects against diet-induced oxidative stress and neuroinflammation. Methods: Forty-eight male Wistar rats were randomly divided into eight groups (n = 6). Group 1 (control) received a standard diet, while group 2 received a high-fat, high-sucrose diet (HFSD). Groups 3, 4, 5, 6, 7, and 8 were also fed HFSD supplemented with C. citrinus extract, its main compounds, and a mixture of these compounds administered once daily via oral cannula for 23 weeks. The antioxidant and pro-inflammatory enzymes, along with oxidative biomarkers, were evaluated in the brains of the rats. Results:
C. citrinus leaf extract and its four main components, both separately and together, modulated the activities of catalase, superoxide dismutase, glutathione peroxidase, and paraoxonase-1. They also affected levels of reduced glutathione while decreasing the amounts of advanced oxidative protein products, malondialdehyde, and 4-hydroxynonenal. Additionally, they decreased the activities of cyclooxygenase (COX-1 and COX-2), 5-lipoxygenase, xanthine oxidase, and myeloperoxidase in the brains of rats, despite a high-fat-sucrose diet. Conclusions: These results show that the main compounds in C. citrinus leaf extract are essential for its antioxidant and anti-inflammatory effects, which help protect against oxidative stress in the brains of rats on a high-calorie diet.

## Linked entities

- **Proteins:** COX1 (cytochrome c oxidase subunit I), COX2 (cytochrome c oxidase subunit II), Cat (Catalase), GPX2 (glutathione peroxidase 2)
- **Chemicals:** d-limonene (PubChem CID 440917), gallic acid (PubChem CID 370), ellagic acid (PubChem CID 5281855), p-coumaric acid (PubChem CID 637542), malondialdehyde (PubChem CID 10964), 4-hydroxynonenal (PubChem CID 5283344), reduced glutathione (PubChem CID 745)
- **Diseases:** obesity (MONDO:0011122), neuroinflammation (MONDO:0004466)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Alox5 (arachidonate 5-lipoxygenase) [NCBI Gene 25290] {aka 5-LOX, LOX5A}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, Pon1 (paraoxonase 1) [NCBI Gene 84024], Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, COX1 (cytochrome c oxidase subunit I) [NCBI Gene 26195] {aka COI}, Mpo (myeloperoxidase) [NCBI Gene 303413]
- **Diseases:** inflammation (MESH:D007249), neuroinflammation (MESH:D000090862), obesity (MESH:D009765)
- **Chemicals:** d-limonene (MESH:D000077222), malondialdehyde (MESH:D008315), gallic acid (MESH:D005707), 4-hydroxynonenal (MESH:C027576), Sucrose (MESH:D013395), Fat (MESH:D005223), C. citrinus extract (-), p-coumaric acid (MESH:C495469), glutathione (MESH:D005978), ellagic acid (MESH:D004610)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12844200/full.md

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Source: https://tomesphere.com/paper/PMC12844200