Icariside II, a novel phosphodiesterase-5 inhibitor, attenuates streptozotocin-induced cognitive deficits in rats.
Beta-amyloid (Aβ) deposition and neuroinflammation are involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and Aβ levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive deficits, Aβ levels and neuroinflammation induced by intracerebroventricular-streptozotocin (ICV-STZ) in rats. The results demonstrated that ICV-STZ exhibited cognitive deficits and neuronal morphological damage, along with Aβ increase and neuroinflammation in the rat hippocampus. ICS II improved cognitive deficits, attenuated neuronal death, and decreased the levels of Aβ1-40, Aβ1-42 and PDE5 in the hippocampus of STZ rats. Furthermore, administration of ICS II at the dose of 10mg/kg for 21days significantly suppressed the expression of beta-amyloid precursor protein (APP), beta-secretase1 (BACE1) and increased the expressions of neprilysin (NEP) together with inhibited interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) and transforming growth factor-β1 (TGF-β1) levels. In addition, ICS II exerted a beneficial effect on inhibition of IκB-α degradation and NF-κB activation induced by STZ. Taken together, the present study demonstrated that ICS II was a potential therapeutic agent for AD treatment.
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Caixia
C
Yin
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Yuanyuan
Y
Deng
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Jianmei
J
Gao
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Xiaohui
X
Li
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Yuangui
Y
Liu
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China. Electronic address: gqh@zmc.edu.cn.
Qihai
Q
Gong
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D005419:Flavonoids; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D058986:Phosphodiesterase 5 Inhibitors; C060988:baohuoside I; D013311:Streptozocin
Alzheimer’s disease; beta-amyloid; icariside II; neuroinflammation; phosphodiesterase-5; streptozotocin