Study on the Ameliorative Effect of Icariin Mediating NO/cGMP/PKGI Signalling Pathway in Alzheimer's Disease.

ABSTRACT

Objective: To investigate the effect of icariin (ICA) on cognitive function and NO/cGMP/PKGI signaling pathway in mice with Alzheimer's disease (AD). Methods: Wild-type C57BL/6 mice were used as the Control group, and APP/PS1 double transgenic mice were used to establish the AD model. The mice were randomly divided into AD group, AD+L-icariin group (10 mg/kg), and AD+H-icariin group (40 mg/kg), with 10 mice in each group. Water maze and Y-maze tests were used to evaluate the learning and memory abilities of mice. ELISA was used to measure the levels of serum Aß and cGMP. Tunel staining was used to determine the apoptosis of neurons in the hippocampus. Immunohistochemistry was used to measure the expression of Brdu, Dcx, and NeuN in the hippocampus. The protein expressions of iNOS, sGC, PKGI, Caspase3, Bax, and Bcl-2 in brain tissue were determined by Western blot. Results: Compared with the control group, the learning and memory ability of the AD group was significantly decreased, the serum levels of Aß and cGMP were increased, the neuronal apoptosis was increased, the contents of Brdu, Dcx and NeuN were decreased, the expression of iNOS, sGC, PKGI, Caspase-3 and Bax proteins was increased, and the expression of Bcl-2 protein was decreased (P < .05). Compared with the AD group, the AD mice treated with icariin (40mg/kg) showed improved learning and memory abilities, decreased serum Aß and cGMP contents, decreased neuronal apoptosis, increased Brdu, Dcx, and NeuN contents, and decreased iNOS, sGC, PKGI, Caspase-3, and Bax protein expressions. The expression of Bcl-2 protein was increased (P < .05). Conclusion: Icariin improves AD in mice by activating the NO/cGMP/PKGI signaling pathway.