β-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in asenescence-accelerated prone 8 mice.
β-Asarone is an active component of the Acori graminei rhizome that is a traditional Chinese medicine clinically used in treating dementia in China. However, the cognitive effect of β-asarone and its mechanism has remained elusive. Here, we used asenescence-accelerated prone 8 (SAMP8) mice, which mimic many of the salient features of Alzheimer׳s disease (AD), to further investigate whether modulation of the ROCK signaling pathway and/or autophagy, synaptic loss is involved in the effects of β-asarone on learning and memory. SAMP8 mice at the age of 6 months were intragastrically administered by β-asarone or a vehicle daily for 2 months. Senescence-accelerated-resistant (SAMR1) mice were used as the control. Our results demonstrate that autophagy and ROCK expression were increased significantly in 8 months SAMP8 mice, which were concomitant with that SAMP8 mice at the same age displayed a significant synaptic loss and cognitive deficits. The up-regulation of ROCK expression and autophage in the hippocampus of SAMP8 were significantly reduced by β-asarone, and prevents synaptic loss and improved cognitive function of the SAMP8 mice. β-asarone decreased neuronophagia and lipofuscin in the hippocampus of SAMP8 mice, but did not reduce Aβ42 levels and malondialdehyde levels and superoxide dismutase activities. Moreover, suppression of ROCK2 by siRNA significantly reduced the effects of β-asarone on the autophage and synaptic proteins expression in PC12 cells damage induced by Aβ1-40. Taken together, β-asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice.
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Yunbo
Y
Chen
Research and Development of New Drugs, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Gang
G
Wei
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Hui
H
Nie
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Yaping
Y
Lin
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Huijuan
H
Tian
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Yu
Y
Liu
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Xuhua
X
Yu
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Shuyi
S
Cheng
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Rong
R
Yan
Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China. Electronic address: wangqi@gzucm.edu.cn.
Qi
Q
Wang
Research and Development of New Drugs, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Dong Hui
DH
Liu
Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Weiye
W
Deng
Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Yingtao
Y
Lai
Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Jian Hong
JH
Zhou
Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Sai Xia
SX
Zhang
Research and Development of New Drugs, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Wei Wei
WW
Lin
Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China. Electronic address: CDF27212@21cn.com.
Dong Feng
DF
Chen
D019588:Aging, Premature / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D000840:Anisoles / Q000494:pharmacology / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D056654:CA3 Region, Hippocampal / Q000737:chemistry / Q000187:drug effects*; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D008062:Lipofuscin / Q000032:analysis; D017774:Long-Term Potentiation / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000032:analysis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000032:analysis; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides; D000840:Anisoles; D004365:Drugs, Chinese Herbal; D008062:Lipofuscin; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); C012195:asarone; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C580818:ROCK2 protein, rat; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases
Autophagy; Dementia; ROCK; Synapse; β-Asarone