Aging is caused by an imbalance between antioxidants and ROS. Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates antioxidant genes. Under normal conditions, Nrf2 will bind keap1 and cause degradation of Nrf2. Nrf2 activation can be stimulated by secondary metabolites, such as glucosinolate (glucoraphanin and sulforaphane) and phenolic (kaempferol and quercetin) groups found in broccoli (Brassica oleracea). The purposes of this study were to analyze the interaction of the four compounds with Keap1 through molecular docking, to identify interactions that inhibit Keap1, and also to know the bioactivity scores, drug-likeness, and bioactivity prediction of each compound. The Nrf2-Keap1 protein (ID: 2FLU) structure was retrieved from the protein database, whereas the quercetin (CID: 5280343); kaempferol (CID: 5280863), sulforaphane (CID: 5350), and glucoraphanin (CID: 656556) were obtained from the PubChem Database. Molecular docking was done with HEX 8.0. The docking results were visualized with Discovery Studio 2020. Drug-likeness and bioactivity scores of the compounds were identified using mollinspiration. Prediction of bioactivity was carried out with PASS Online. The results showed that the binding energy of quercetin with Keap1 was -268.72 kcal.mol -1 , and glucoraphanin with Keap1 was -318.01 kcal.mol -1 . We found that quercetin from the phenolic group and glucoraphanin from the glucosinolate group had a strong interaction with Keap1, indicated by the number of interactions occurred and the smaller energy needed. Hence both compounds could inhibit the interaction of Keap1-Nrf2. Consequently, Nrf2 could transcribe antioxidant genes. The interaction between Keap1 and quercetin may play a role related to ROS reduction activities, such as enhancing HMOXI expression. This study indicates that quercetin has more potential in drug development as peroxidase inhibitors.
Restraint stress causes changes in the brain parameters. Little research has been done on the impact of restraint stress on other tissues, including adrenal glands and kidneys. This study aimed to determine the effect of restraint stress on eating behaviors, depressive-like, anxiety-like behaviors, weight gain as well as histopathological changes in the kidneys and adrenal glands. Twenty adult BALB/c mice were assigned into control male, stressed male, control female, and stressed female. Restraint stress was applied two hours/day for 14 days. Tail suspension and open field tests were carried out to perform behavior analyses. Adrenal and kidney histological slides were observed under an Olympus CX-31 microscope and visualized using an Olympus E330 camera. The two-way ANOVA test was used for statistical analysis using GraphPad Prism 9.0.0 software. We found that restraint stress defeat appetite and reduces weight gain particularly in stressed female. However, depressive- and anxiety-like behavior were demonstrated in both sexes. Adrenal and kidney tissues of stressed mice demonstrated a higher number of necrotic cells than control. The pyknosis phase was more common than the karyorrhexis and karyolitic phases. Interestingly, male mice were more receptive to stress than female mice. These findings indicate that restraint stress leads to behavioral changes and cellular defects in the adrenal glands and kidneys, particularly in male mice. The sympathetic activation and hypothalamus-pituitary-axis stimulation are assumed as the underlying stress effect of the restraint procedure. The restraint stress method has the potential to be used in future research on stress-responsive target organs.
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