Neuroprotective effects of tenuigenin on neurobehavior, oxidative stress, and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats

• Main Authors: Xiao-Bo Huang, Yu-Jing Chen, Wen-Qiang Chen, Ning-Qun Wang, Xi-Ling Wu, Yan Liu
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2018-01-01
• Series: Brain Circulation
• Subjects: Intracerebroventricular streptozotocin; oxidative stress; tau hyperphosphorylation; tenuigenin
• Online Access: http://www.braincirculation.org/article.asp?issn=2394-8108;year=2018;volume=4;issue=1;spage=24;epage=32;aulast=Huang
• ISSN: 2394-8108; 2455-4626

BACKGROUND: Tenuigenin (TEN), a major active component of the Chinese herb Polygala tenuifolia root, has been used to improve memory and cognitive function in Traditional Chinese Medicine for centuries. PURPOSE: The present study was designed to explore the possible neuroprotective effect of TEN on the streptozotocin (STZ)-induced rat model of sporadic Alzheimer's disease (sAD). METHODS: STZ was injected twice intracerebroventrically (3 mg/kg, ICV) on alternate days (day 1 and day 3) in Rats. Daily treatment with TEN (2, 4, and 8 mg/kg) starting from the first dose of STZ for 28 days. Memory-related behaviors were evaluated using the Morris water maze test. Hyperphosphorylation of tau proteins in hippocampus were measured by western blot assay. Superoxide dismutase activities, malondialdehyde, glutathione peroxidase and 4-hydroxy-2-nonenal adducts contents were also measured in the hippocampus.RESULTS: Treatment with TEN significantly improved STZ-induced cognitive damage, markedly reduced changes in malondialdehyde and 4-hydroxy-2-nonenal adducts, and significantly inhibited STZ-induced reduction in superoxide dismutase and glutathione peroxidase activities in the hippocampus. In addition, TEN decreased hyperphosphorylation of tau resulting from intracerebroventricular STZ (ICV-STZ) injection, and Nissl staining results showed that TEN has protective effects on hippocampal neurons. CONCLUSION: These results provide experimental evidence demonstrating preventive effect of TEN on cognitive dysfunction, oxidative stress, and hyperphosphorylation of tau in ICV-STZ rats. This study indicates that TEN may have beneficial effects in the treatment of neurodegenerative disorders such as AD.