The Relieving Effect of Isorhynchophylline on Learning and Memory Impairment Induced by Aluminum Chloride(AlCl3) in Mice
Refereed conference paper presented and published in conference proceedings



摘要Alzheimer’s disease (AD) is the most common form of dementia in elderly people with huge health and economic burden to the society. So far, the treatment for AD is largely unsatisfactory. Isorhynchophylline (IRN) is a c-22 oxindole alkaloid that was isolated from Uncaria. rhynchophylla (Gou-Teng in Chinese). Recent studies in our laboratory have shown that IRN has potent neuroprotective effects in different in vivo and in vitro models of AD. To provide more scientific rationale and justification for future clinical study on this anti-AD alkaloid, the present project aimed to investigate the cognitive deficit ameliorating effects of IRN on aluminum chloride (AlCl3)-induced AD mice.
Methods: To induce AD model, four-month-old male Balb-c mice were subcutaneously injected with AlCl3 (50 mg/kg) daily for 8 consecutive weeks. At the same time, mice were intragastrically given IRN (20 and 40 mg/kg) or donepezil (5 mg/kg, positive control) 30 min before each AlCl3 injection. The spatial learning and memory function was assessed with radial eight-arm maze. The mechanism underlying the anti-AD action of IRN was examined by measuring the parameters of oxidative stress, cholinergic system, apoptosis and nuclear factor kappa B (NF-ĸB) pathway in the brain tissues of AlCl3-treated mice.
Results: The results showed that treatment with IRN could significantly ameliorate the cognitive deficits induced by AlCl3 in mice. In addition, it was found that IRN treatment also enhanced the activities of superoxide dismutases (SOD) and catalase (CAT) and the level of glutathione (GSH), but markedly inhibited the activity of acetylcholinesterase (AChE) and level of malondialdehyde (MDA) in the brain tissues of the AlCl3-treated mice. Moreover, IRN could significantly inhibit the phosphorylation of NF-ĸB p65 and IĸBα in the brain tissues of AlCl3-treated mice. However, IRN did not show significant effect on the activity of BuChE or the protein levels of Bcl-2/Bax.
Conclusion: Our findings indicated that IRN has therapeutic effects on AlCl3-induced AD mice. The protective effect of IRN against AlCl3-induced AD is probably mediated, at least in part, through inhibiting the AChE activity and enhancing the antioxidant status of brain tissue via suppression the NF-ĸB pathway. These results suggested that IRN is a potential anti-AD drug and contributed to a better understanding of the in vivo anti-AD mechanism of IRN.
著者Li HQ, Lin ZX
會議名稱The 10th Pong Ding Yuen International Symposium on Traditional Chinese Medicine
會議地點Hong Kong

上次更新時間 2018-20-06 於 11:35