Mechanism of Icariin in Ameliorating Neuronal and Dendritic Damage in Alzheimer's Disease by Regulating RhoA/ROCK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of icariin on the recombinant Ras homolog family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway in rats with Alzheimer's disease （AD）， and to explore the mechanism of icariin in ameliorating the neuronal and dendritic damage. MethodThe β-amyloid 1-42 （Aβ1-42， 2.5 g·L-1） was used to induce AD in rats via lateral ventricle injection， and the rats were divided into a model group， a low-dose icariin group （0.03 g·kg-1）， a middle-dose icariin group （0.06 g·kg-1）， a high-dose icariin group （0.09 g·kg-1）， and a control group. The control group and the model group were given an equal volume of normal saline at a dose of 10 mL·kg-1. The cognitive function of rats was assessed by the Morris water maze. The pathological morphology of the rat hippocampal CA1 area was observed by Nissl staining. Dendritic spine density and dendritic length in the CA1 region of the hippocampus were observed by Golgi-Cox staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. Western blot assay was used to detect the protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus. ResultAs compared with the control group， the escape latency of the rats in the model group was increased （P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were decreased （P<0.01）. As compared with the model group， the escape latency of the rats in the middle and high-dose icariin groups was decreased （P<0.05， P<0.01）， while the number of crossing the platform and the dwelling time in the target quadrant were increased （P<0.05， P<0.01）. As compared with the control group， the number of neurons， dendritic spine density， and dendritic length in the hippocampal CA1 area of the rats in the model group were decreased （P<0.01）. As compared with the model group， the number of neurons， dendritic spine density， and dendritic length in the hippocampus of the rats in the middle and high-dose icariin groups were increased （P<0.05， P<0.01）. As compared with the control group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the model group were increased （P<0.01）. As compared with the model group， the mRNA and protein expression levels of TNF-α， IL-1β， IL-6， RhoA， ROCK1， and ROCK2 in the hippocampus of the rats in the middle and high-dose icariin groups were decreased （P<0.05， P<0.01）. ConclusionIcariin improves cognitive function and neuronal and dendritic damage in AD by inhibiting the RhoA/ROCK signaling pathway.

Important role of Rho/ROCK2 pathway in the development of Alzheimer′s disease / 国际药学研究杂志

Rho/ROCK pathway is a ubiquitous singling pathway in organisms,and is involved in many biological processes. In the brain of Alzheimer′s patients,the activities of Rho and Rho associated coiled coil forming protein kinase(ROCK)are up-regulat?ed,which is accompanied by the elevation of Aβ42 level,and the abnormal change of the morphology and function of neuronal process?es,suggesting that the occurrence and development of Alzheimer′s disease(AD)is associafed with the overexpression and excessive activation of Rho or ROCK. Rho/ROCK2 pathway is considered a target pathway for the prevention and treatment of AD,and Rho or ROCK2 also becomes an important target for AD drug development. Numerous studies have revealed that suppressing the expression or decreasing the activity of Rho or ROCK2 can reduce Aβ42-induced neurotoxicity,protect neurons,and slow down the occurrence and de?velopment of AD. Therefore,specific inhibition of ROCK2 has an important significance for the repair of central nervous system dam?age and the treatment of AD. This article reviews several effects of Rho/ROCK2 pathway on the development of AD.

Important role of Rho/ROCK2 pathway in the development of Alzheimer’s disease / 国际药学研究杂志

Rho/ROCK pathway is a ubiquitous singling pathway in organisms, and is involved in many biological processes. In the brain of Alzheimer’s patients, the activities of Rho and Rho associated coiled coil forming protein kinase(ROCK)are up-regulated, which is accompanied by the elevation of Aβ42 level, and the abnormal change of the morphology and function of neuronal processes, suggesting that the occurrence and development of Alzheimer’s disease(AD)is associafed with the overexpression and excessive activation of Rho or ROCK. Rho/ROCK2 pathway is considered a target pathway for the prevention and treatment of AD, and Rho or ROCK2 also becomes an important target for AD drug development. Numerous studies have revealed that suppressing the expression or decreasing the activity of Rho or ROCK2 can reduce Aβ42-induced neurotoxicity, protect neurons, and slow down the occurrence and de velopment of AD. Therefore, specific inhibition of ROCK2 has an important significance for the repair of central nervous system damage and the treatment of AD. This article reviews several effects of Rho/ROCK2 pathway on the development of AD.