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Background <p>Depression is associated with oxidative stress and neurochemical imbalances, highlighting the need for novel therapeutic strategies. Berberine (BBR) has potential antidepressant effects but suffers from poor bioavailability. This study aimed to develop and evaluate BBR-loaded phytosomes (BBR-PS) as an advanced delivery system targeting reactive oxygen species (ROS) in a chronic stress model.</p> Research Design and Methods <p>BBR-PS was prepared using thin-film hydration with varying drug-lipid-cholesterol ratios. The optimized formulation was characterized for vesicle size, zeta potential, entrapment efficiency(%EE), drug loading (%DL) and in-vitro drug release. Morphology was assessed via FESEM and HRTEM. Antidepressant efficacy was evaluated in Wistar rats using the Chronic Unpredictable Mild Stress (CUMS) model. Biochemical markers (corticosterone, MDA, GSH, CAT) were analyzed, and statistical comparisons were made between treatment groups.</p> Results <p>The optimized BBR-PS formulation exhibited a vesicle size of 107&#xa0;nm, zeta potential of -33.2 mV, %EE of 73% and %DL i.e., 14.6%, with sustained in-vitro release. In-vivo studies demonstrated that BBR-PS significantly reduced serum corticosterone (23.035 ng/ml) and hippocampal MDA levels (MDA: 0.35 ± 0.01 nmoles/mg) while increasing GSH ( 0.0017 ± 0.0009 nM/mg) and CAT activity (1.24 ± 0.04 U/mg) compared to pure BBR-solution, indicating enhanced neuroprotection and ROS modulation.</p> Conclusions <p>BBR-PS improved bioavailability, antioxidant activity, and antidepressant efficacy in a chronic stress model. While promising, further clinical studies are needed to validate these findings and assess long-term safety. This delivery system presents a potential breakthrough in depression therapy via targeted ROS regulation.</p> Graphical Abstract <p></p>

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Exploring the Therapeutic Potential of Berberine Loaded Phytosomes Against Depression Through Preclinical Studies: Evidences from Behavioural & Biochemical Studies Using CUMS Model in Wistar Rats

  • 期刊论文

  • 发表日期：

    2025年10月17日

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  • Shivani Sharma,
  • Sunil Bharti,
  • Pemal Preet Kaur,
  • Namarta Thakur,
  • Amita Sarwal

摘要

Background

Depression is associated with oxidative stress and neurochemical imbalances, highlighting the need for novel therapeutic strategies. Berberine (BBR) has potential antidepressant effects but suffers from poor bioavailability. This study aimed to develop and evaluate BBR-loaded phytosomes (BBR-PS) as an advanced delivery system targeting reactive oxygen species (ROS) in a chronic stress model.

Research Design and Methods

BBR-PS was prepared using thin-film hydration with varying drug-lipid-cholesterol ratios. The optimized formulation was characterized for vesicle size, zeta potential, entrapment efficiency(%EE), drug loading (%DL) and in-vitro drug release. Morphology was assessed via FESEM and HRTEM. Antidepressant efficacy was evaluated in Wistar rats using the Chronic Unpredictable Mild Stress (CUMS) model. Biochemical markers (corticosterone, MDA, GSH, CAT) were analyzed, and statistical comparisons were made between treatment groups.

Results

The optimized BBR-PS formulation exhibited a vesicle size of 107 nm, zeta potential of -33.2 mV, %EE of 73% and %DL i.e., 14.6%, with sustained in-vitro release. In-vivo studies demonstrated that BBR-PS significantly reduced serum corticosterone (23.035 ng/ml) and hippocampal MDA levels (MDA: 0.35 ± 0.01 nmoles/mg) while increasing GSH ( 0.0017 ± 0.0009 nM/mg) and CAT activity (1.24 ± 0.04 U/mg) compared to pure BBR-solution, indicating enhanced neuroprotection and ROS modulation.

Conclusions

BBR-PS improved bioavailability, antioxidant activity, and antidepressant efficacy in a chronic stress model. While promising, further clinical studies are needed to validate these findings and assess long-term safety. This delivery system presents a potential breakthrough in depression therapy via targeted ROS regulation.

Graphical Abstract