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

<b>Background</b>: 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 <i>Callistemon citrinus</i>, 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 <i>C. citrinus</i> leaf extract responsible for its neuroprotective effects against diet-induced oxidative stress and neuroinflammation. <b>Methods:</b> 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 <i>C. citrinus</i> 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. <b>Results:</b><i>C. citrinus</i> 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. <b>Conclusions:</b> These results show that the main compounds in <i>C. citrinus</i> 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.