Pharmacological investigation of taxifolin for its therapeutic potential in depression

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 mu g/Kg) for 14 alternative days. Rats (n = 6/group) were randomly assigned to four groups: (i) Saline/Control, (ii) Disease (LPS 500 mu g/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- alpha, NF- kappa b, IL -6 and COX -2, while significantly upregulating and activating the protective PPAR- gamma 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- gamma pathway.