Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response

摘要

Abstract Silymarin is a polyphenolic flavonoid of Silybum marianum , exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique. Wistar rats were administered with silymarin at a dose of 100 mg/kg and 200 mg/kg, by per oral in OBX and sham operated rats. Behavioral (ambulatory and rearing activity and immobility time), neurochemical [serotonin (5-HT), dopamine (DA), norepinephrine (NE) and brain derived neurotrophic factor (BDNF) level], biochemical (MDA formation, IL-6, TNF-α and antioxidants) changes in hippocampus and cerebral cortex along with serum corticosterone were investigated. Rats subjected to OBX elicited significant increase in immobility time, ambulatory and rearing behaviors, reduced BDNF level, 5-HT, DA, NE and antioxidant parameters along with increased serum corticosterone, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex compared to sham operated rats. Administration of with silymarin significantly attenuated immobility time, ambulatory and rearing behaviors, serum corticosterone and improved BDNF expression, 5-HT, DA, NE and antioxidant paradigms in cerebral cortex as well as hippocampus. In addition, silymarin attenuated IL-6, and TNF-α significantly in hippocampus and cerebral cortex in OBX rats. Thus, silymarin exhibits anti-depressant-like activity in OBX rats due to alterations in several neurotransmitters, endocrine and immunologic systems, including BDNF, 5-HT, DA, NE, MDA formation, IL-6, and TNF-α in hippocampus and cerebral cortex as well as serum corticosterone. Graphical abstract Display Omitted Highlights ? OBX-induced behavioral, biochemical and neurochemical alterations in rats ? Impaired monoamines, BDNF, antioxidants activity due to OBX in hippocampus and cortex ? Silymarin attenuate behavioral changes along with improved monoamines, BDNF and antioxidants ? Silymarin reduced TNF-α, IL-6, MDA in hippocampus, cortex and serum corticosterone ? Silymarin exhibit antidepressant like activity by its effects on monoamines, BDNF level, TNF-α, IL-6 and reduce oxidative stress. ]]>