Background: A high fat diet (HFD)is one of the main causes of obesity and is closely linked to metabolic disorders brought on by stress and malfunctioning tissues. Propolis (Trigona Honey) is considered to be helpful in treating inflammatory diseases because it has also been demonstrated to have anti-inflammatory and anti-free radical properties. This study to demonstrate how much propolis supplementation affects BW, NF-κB, CysC, and ACE2 levels in Wistar rats (Rattus norvegicus) fed a HFD. Methods: Post-test and control group designs in an experimental setup. A total of twenty-four rats were randomly assigned to four groups of six. Group I received a normal diet for sixteen weeks (ND), Group II received a high fat diet (HFD) for sixteen weeks (HFD), Group III received an HFD for sixteen weeks plus propolis for eight weeks (HFD-8), and Group IV received an HFD and propolis for sixteen weeks (HFD-16). Using the Enzyme-Linked Immunosorbent Assay (ELISA), body weight (BW), serum NF-κB, Cys C, and ACE2 levels were measured before treatment (week 0), after 8 weeks of HFD (HFD-8) (week 8), and after 16 weeks of HFD (HFD-16). Results: The mean starting weight in the ND, HFD, HFD-8, and HFD-16 groups did not differ significantly (p > 0.001). By week eight, the HFD group's body weight had increased considerably (254.83 grams vs. 202.0 grams) in comparison to the ND group (p<0.001). The HFD and HFD-8 groups' body weight increased significantly at week 16 in comparison to the ND group (334.83 grams and 269.50 grams vs. 208.67 grams) (p<0.001). At week 16, there was no discernible difference in mean BW between ND and HFD-16 (p > 0.001). There was no significant difference found in the mean initial NF-κB levels between the ND, HFD, HFD-8, and HFD-16 groups (p > 0.001). At week 8, NF-κB levels in the HFD group were significantly higher (5,038 ng/ml vs. 3,655 ng/ml) (p<0.001) than in the ND group. At week 16, NF-κB levels in the HFD and HFD-8 groups were notably higher than those in the ND group (p<0.001), at 6,136 ng/ml and 4,378 ng/ml, respectively, compared to 3,775 ng/ml. Between ND and HFD-16, there was no significant distinction in the mean NF-κB levels at week 16 (p>0.001). There was no significant difference observed in the mean CysC and ACE2 between the ND, HFD, HFD-8, and HFD-16 groups (p > 0.001). CysC and ACE2 levels in the HFD group were significantly higher than those in the ND group at week 8, and in the HFD and HFD-8 groups, they were significantly higher than those in the ND group at week 16. When propolis is administered for eight weeks, the rise in BW, NF-κB, CysC, and ACE2 is suppressed until the eighth week, at which point it increases once more until the sixteenth week. Propolis administration, however, will halt the rise in BW, NF-κB, CysC, and ACE2 until the sixteenth week. Conclusion: Propolis administration for 16 weeks can suppress the increase in BW, LI, RI, NF-κB, CysC and ACE2 levels in rats given a high fat diet (HFD).
