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Abstract：
The current study aimed to investigate the influence of taxifolin on depression symptoms alleviation in Male Sprague-Dawley rats by targeting underlying pathways of depression. Molecular docking analyses were conducted to validate taxifolin\'s binding affinities against various targets. In silico analysis of taxifolin revealed various aspects of post docking interactions with different protein targets. Depression was induced in rats via intraperitoneal injection of Lipopolysaccharide (LPS; 500 μ g/Kg) for 14 alternative days. Rats (n = 6/group) were randomly assigned to four groups: (i) Saline/Control, (ii) Disease (LPS 500 μg/kg), (iii) Standard (fluoxetine 20 mg/kg), and (iv) Treatment (taxifolin 20 mg/kg). At the end of the in vivo study, brain samples were used for biochemical and morphological analysis. Taxifolin exhibited neuroprotective effects, as evidenced by behavioral studies, antioxidant analysis, histopathological examination, immunohistochemistry, ELISA and RT PCR, indicating an increase number of surviving neurons, normalization of cell size and shape, and reduction in vacuolization. Taxifolin also decreased inflammatory markers such as TNF-α, NF-κb, IL-6 and COX-2, while significantly upregulating and activating the protective PPAR-γ pathway, through which it reduces the oxidative stress, neuroinflammation, neurodegeneration, thereby ameliorating depression symptoms in experimental rat model of depression. Our finding suggests that taxifolin act as neuroprotective agent partially mediated through PPAR-γ pathway.
摘要：
本研究旨在通过靶向潜在的抑郁途径,探讨花旗松素对雄性SD大鼠抑郁症状缓解的影响。进行了分子对接分析以验证taxifolin对各种靶标的结合亲和力。紫杉素的计算机模拟分析揭示了对接后与不同蛋白质靶标相互作用的各个方面。通过腹膜内注射脂多糖（LPS；500μg/Kg）14天来诱导大鼠抑郁。大鼠（n=6/组）随机分为四组：（i）盐水/对照组，（ii）疾病（LPS500μg/kg），（iii）标准品（氟西汀20mg/kg），和(iv)治疗(紫杉素20mg/kg)。在体内研究结束时，脑样本用于生化和形态学分析.Taxifolin表现出神经保护作用，正如行为研究所证明的那样，抗氧化剂分析,组织病理学检查,免疫组织化学，ELISA和RTPCR，表明存活的神经元数量增加，细胞大小和形状的归一化，并减少空泡化。Taxifolin还降低了炎症标志物，如TNF-α，NF-κb,IL-6和COX-2，同时显著上调和激活保护性PPAR-γ途径，通过它减少了氧化应激，神经炎症，神经变性,从而改善实验性抑郁症大鼠模型的抑郁症状。我们的发现表明，紫杉素部分通过PPAR-γ途径介导作为神经保护剂。
