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. 2025 Jun 16;50(4):203.
doi: 10.1007/s11064-025-04447-2.

Assessment of the Therapeutic Potential of Hesperidin and Quercetin Nanoparticles on Oxidative Stress, Enzyme Activities, Trophic Factors, and Monoamines in an Animal Model of Depression

Haitham S Mohammed  1 , Eman N Hosny  2 , Hussein G Sawie  2 , Yasser A Khadrawy  3
Affiliations

Assessment of the Therapeutic Potential of Hesperidin and Quercetin Nanoparticles on Oxidative Stress, Enzyme Activities, Trophic Factors, and Monoamines in an Animal Model of Depression

Haitham S Mohammed et al. Neurochem Res. .

Abstract

Natural remedies have emerged as promising alternative or complementary therapies for combating depression. This study aimed to investigate the effects of hesperidin (HSP-NPs) and quercetin (QUR-NPs) nanoparticles on oxidative stress markers, enzyme activities, brain-derived neurotrophic factor, and monoamine levels in the cortex and hippocampus of a reserpine-induced rat model of depression. The depression model was established by administering reserpine (0.2 mg/kg) to the animals for 25 days. On the 26th, rats were administered i.p. with reserpine (0.1 mg/kg) and oral isotonic saline solution for another 21 days. Following reserpine administration, the animals exhibited a significant reduction in nitric oxide (NO), reduced glutathione (GSH), brain-derived neurotrophic factor (BDNF), serotonin (5-HT), norepinephrine (NE), and dopamine (DA) levels. Additionally, a significant decrease in Na, K,ATPase activity and a significant increase in acetylcholinesterase (AchE) and monoamine oxidase (MAO) activity were observed in the cortex and hippocampus as compared to the control group of animals. Treatment with either HSP-NPs and QUR-NPs for 14 days mitigated the oxidative stress in the cortex and hippocampus. The treatments restored the changes Na, K,ATPase, and MAO, AchE activities in the two brain regions. Notably, QUR-NPs was superior in alleviating the adverse changes induced by reserpine concerning monoamines and BDNF levels. These findings highlight the therapeutic potential of HSP-NPs and QUR-NPs in mitigating the underlying etiology of depressive symptoms rat model. Further investigations are warranted to exploAuthorre the potential synergistic effects of hesperidin and quercetin when used in combination at different doses and treatment durations.

Keywords: BDNF; Depression; Hesperidin; Monoamines; Oxidative stress; Quercetin.

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Conflict of interest statement

Declarations. Ethical Approval: Animal’s care and experimental design were approved by the Proposal Research Ethics Committee, Faculty of Science Ain Shams University and the approval number was ASU-SCI/PHYS/2023/3/1. Competing Interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
TEM image of HSP-NPs and QUR-NPs
Fig. 2
Fig. 2
Effect of HSP-NPs and QUR-NPs on the activity of Na, K,ATPase, acetylcholinesterase (AchE) and monoamine oxidase (MAO) in the cortex of rat model of depression induced by reserpine. Statistically significant means (p-value formula image 0.05) are given different letters and statistically significant means are given similar letters
Fig. 3
Fig. 3
Effect of HSP-NPs and QUR-NPs on the activity of Na, K,ATPase, acetylcholinesterase (AchE) and monoamine oxidase (MAO) in the hippocampus of rat model of depression induced by reserpine. Statistically significant means (p-value formula image 0.05) are given different letters and statistically significant means are given similar letters
Fig. 4
Fig. 4
Effect of HSP-NPs and QUR-NPs on the level of brain derived neurotrophic factor (BDNF) in the cortex and hippocampus of rat model of depression induced by reserpine. Statistically significant means (p-value formula image 0.05) are given different letters and statistically significant means are given similar letters
Fig. 5
Fig. 5
Effect of HSP-NPs and QUR-NPs on the levels of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) in the cortex of rat model of depression induced by reserpine. Statistically significant means (p-value formula image 0.05) are given different letters and statistically significant means are given similar letters
Fig. 6
Fig. 6
Effect of HSP-NPs and QUR-NPs on the levels of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) in the hippocampus of rat model of depression induced by reserpine. Statistically significant means (p-value formula image 0.05) are given different letters and statistically significant means are given similar letters
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