Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus.

Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1ß and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.

Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1ß, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other neuropsychiatric disorders associated with inflammation and oxidative stress.