Mitigation of oxidative stress with dihydroactinidiolide, a natural product against scopolamine-induced amnesia in Swiss albino mice.

The present work describes the neuroprotective efficacy of DHAc under escalated oxidative stress condition in scopolamine-induced amnesic mice. During the toxicity test of DHAc in mice, the acute dose (LD50) is found to be 3.468 mg/kg bw and the sub-acute dose is 0.68 mg/kg bw. Improved cognitive and learning abilities are observed in Morris water maze and Y-maze test in 10 days DHAc (0.68 mg/kg bw) treated scopolamine-induced male Swiss albino mice. In the molecular level these changes are monitored as reduced oxidative load followed by significantly lower lipid peroxidation and protein carbonylation, increased superoxide dismutase, catalase, acetylcholinesterase, caspase-3 activity and glutathione content followed by higher expression of anti apoptotic protein bcl-2 in mice brain as compared to scopolamine (1 mg/kg bw) treated mice. Meanwhile real time PCR shows higher expression of brain derived neurotrophic factor (BDNF) and synaptophysin in DHAc pretreated scopolamine treated mice brain. HPLC analysis suggested its possible blood brain barrier crossing ability. Overall DHAc reversed behavioral anomalies in the scopolamine treated mice via oxidative stress quenching, enhancing antioxidative enzyme activity, enhancing BDNF and synaptophysin mRNA levels and reducing expression of apoptotic protein Bax.