Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice.
Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Aβ aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation-induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders.
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Ge
G
Jin
The Eleventh People's Hospital of Shenyang, Shenyang 110101, PR China.
Dafeng
D
Bai
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Shiliang
S
Yin
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Zhihang
Z
Yang
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Dan
D
Zou
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Zhong
Z
Zhang
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Xiaoxiu
X
Li
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China.
Yan
Y
Sun
Department of Pharmacology Shenyang Medical Colleges, Shenyang 110034, PR China. Electronic address: qwzhu18@163.com.
Qiwen
Q
Zhu
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004660:Encephalitis / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage*; D065852:Spatial Memory / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015850:Interleukin-6; C490665:Mapk8ip protein, mouse; D018696:Neuroprotective Agents; D012838:Silymarin; D015847:Interleukin-4; D000077385:Silybin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
Alzheimer’s disease; Microglia; Neuroinflammatory; SAMP8 mice; Silibinin