Journal of Current Pharmacology, ISSN NoIssnPrint print, 0000-0000 online, Open Access
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Original Article

Volume 1, July 2026, e1

Apigenin Mitigates Neurochemical Alterations, Oxidative and Nitrergic Stress Induced in Two-Hit Neurodevelopmental Model of Schizophrenia in Rats

Figures

↓  Figure 1. Effect of APG on locomotor activity of weanling rats subjected to two-hit model of neurodevelopmental psychosis in OFT. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; OFT: open field test; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 1.
↓  Figure 2. Effect of APG on immobility in weanling rats subjected to two-hit model of neurodevelopmental psychosis in FST. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; FST: forced swim test; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 2.
↓  Figure 3. Effect of APG on reduced GSH level in amygdala of weanling rats in two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; GSH: reduced glutathione; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 3.
↓  Figure 4. Effect of APG on GSH level in hippocampus of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; GSH: reduced glutathione; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 4.
↓  Figure 5. Effect of APG on GSH level in Prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; GSH: reduced glutathione; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 5.
↓  Figure 6. Effect of APG on MDA level in amygdala of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; MDA: malondialdehyde; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 6.
↓  Figure 7. Effect of APG on MDA level in hippocampus of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; MDA: malondialdehyde; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 7.
↓  Figure 8. Effect of APG on MDA level in prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; MDA: malondialdehyde; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 8.
↓  Figure 9. Effect of APG on SOD level in amygdala of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; SOD: superoxide dismutase; VEH: vehicle.
Figure 9.
↓  Figure 10. Effect of APG on SOD level in hippocampus of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; SOD: superoxide dismutase; VEH: vehicle.
Figure 10.
↓  Figure 11. Effect of APG on SOD level in Prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; SOD: superoxide dismutase; VEH: vehicle.
Figure 11.
↓  Figure 12. Effect of APG on nitrite level in amygdala of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 12.
↓  Figure 13. Effect of APG on nitrite level in hippocampus of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 13.
↓  Figure 14. Effect of APG on nitrite level in prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 14.
↓  Figure 15. Effect of APG on AChE activity on amygdala of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. AChE: acetylcholinesterase; APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 15.
↓  Figure 16. Effect of APG on AChE activity on hippocampus of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. AChE: acetylcholinesterase; APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 16.
↓  Figure 17. Effect of APG on AChE activity on prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. AChE: acetylcholinesterase; APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 17.
↓  Figure 18. Effect of APG on DA level in Amygdala of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; DA: dopamine; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 18.
↓  Figure 19. Effect of APG on DA level in Hippocampus of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; DA: dopamine; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 19.
↓  Figure 20. Effect of APG on DA level in prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; DA: dopamine; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 20.
↓  Figure 21. Photomicrographs of amygdala showing surviving neurons in weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. APG: apigenin; DN: degenerating neurons; GH: group housed; ISO: isolated; K: karyopyknosis; KET: ketamine; P: pyknosis; RISP: risperidone; VC: vacoulated cytoplasm; VEH: vehicle.
Figure 21.
↓  Figure 22. Neuronal density in amygdala of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 22.
↓  Figure 23. Photomicrographs of hippocampus showing surviving neurons in weanling rats subjected to two-hit model of neurodevelopmental psychosis. APG: apigenin; DN: degenerating neurons; GH: group housed; ISO: isolated; K: karyopyknosis; KET: ketamine; P: pyknosis; RISP: risperidone; VC: vacoulated cytoplasm; VEH: vehicle.
Figure 23.
↓  Figure 24. Neuronal density in hippocampus of weanling rats subjected to Two-Hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 24.
↓  Figure 25. Photomicrographs of prefrontal cortex showing surviving neurons in weanling rats subjected to two-hit model of neurodevelopmental psychosis. APG: apigenin; DN: degenerating neurons; GH: group housed; ISO: isolated; K: karyopyknosis; KET: ketamine; P: pyknosis; RISP: risperidone; VC: vacoulated cytoplasm; VEH: vehicle.
Figure 25.
↓  Figure 26. Neuronal density in prefrontal cortex of weanling rats subjected to two-hit model of neurodevelopmental psychosis. (a) Group-housed animals. (b) Isolated-rearing animals. Bar represents the mean ± SEM of eight animals. *P < 0.05 as compared with KET GH/KET ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. #P < 0.05 as compared with VEH GH/VEH ISO followed by ANOVA and Tukey’s post hoc test for multiple comparisons. APG: apigenin; ANOVA: analysis of variance; GH: group-housed; ISO: isolated; KET: ketamine; RISP: risperidone; SEM: standard error of the mean; VEH: vehicle.
Figure 26.