Current medicinal chemistry · 2026
A functionalized Carbon-based Nano-delivery System for Braintargeted Acteoside: Enhanced Antidepressant Efficacy and Analytical Characterization.
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Huang Liuxuan, Zhang Hongxiu, Tian Haoquan, Yang Wenguang, Fang Xinyu, Ye Han, Ma Ke
Аннотация
INTRODUCTION/OBJECTIVE: The introduction of therapeutics derived from traditional Chinese medicine into the brain is a significant challenge, largely due to the blood- -brain barrier. The authors have assumed that the custom-built delivery system will alter this trend regarding acteoside (ACT). To achieve our purpose, The authors aimed to determine whether conjugation of ACT to a PEGylated nanographene oxide carrier (PEGnGO-ACT) would improve its brain delivery and, subsequently, its antidepressant effect.
METHODS: The authors have synthesized and analyzed the PEG-nGO-ACT composite. The efficacy was subsequently tested on a chemogenetic mouse model of depression, which is based on chronic manipulations of prelimbic cortex activity. Behavioral tests (sucrose consumption, open field, elevated plus maze, forced swim) were used to evaluate outcomes, as well as measures of serum neurotransmitter concentrations and key neuroinflammatory markers.
RESULTS: The PEG-nGO-ACT system demonstrated effective brain targeting. Behavioral test results showed that mice administered PEG-nGO-ACT showed much stronger antidepressant responses compared to mice given free ACT, characterized by a significant reduction in immobility and improvement in anhedonia. On the molecular level, PEG-nGO-ACT therapy was more effective at treating depression-induced imbalances in serum neurotransmitters, particularly by balancing GABA and glutamate levels.
DISCUSSION: The authors have found that the improved performance is not only due to delivery but also to the prolonged, focused release through the nanocarrier. The approach is very effective at converting acteoside into an active drug, which cannot penetrate the brain to a significant degree, into a highly effective treatment that can be applied to a legitimate model of disease.
CONCLUSION: The authors have created a functionalized nanocarrier, PEG-nGO-ACT, that greatly enhances brain-directed delivery and the therapeutic efficacy of acteoside. These results can be interpreted to support PEG-nGO-ACT as a potential nanoplatform for further treatment of depression.
METHODS: The authors have synthesized and analyzed the PEG-nGO-ACT composite. The efficacy was subsequently tested on a chemogenetic mouse model of depression, which is based on chronic manipulations of prelimbic cortex activity. Behavioral tests (sucrose consumption, open field, elevated plus maze, forced swim) were used to evaluate outcomes, as well as measures of serum neurotransmitter concentrations and key neuroinflammatory markers.
RESULTS: The PEG-nGO-ACT system demonstrated effective brain targeting. Behavioral test results showed that mice administered PEG-nGO-ACT showed much stronger antidepressant responses compared to mice given free ACT, characterized by a significant reduction in immobility and improvement in anhedonia. On the molecular level, PEG-nGO-ACT therapy was more effective at treating depression-induced imbalances in serum neurotransmitters, particularly by balancing GABA and glutamate levels.
DISCUSSION: The authors have found that the improved performance is not only due to delivery but also to the prolonged, focused release through the nanocarrier. The approach is very effective at converting acteoside into an active drug, which cannot penetrate the brain to a significant degree, into a highly effective treatment that can be applied to a legitimate model of disease.
CONCLUSION: The authors have created a functionalized nanocarrier, PEG-nGO-ACT, that greatly enhances brain-directed delivery and the therapeutic efficacy of acteoside. These results can be interpreted to support PEG-nGO-ACT as a potential nanoplatform for further treatment of depression.