Intranasal Pretreatment with Z-Ligustilide, the Main Volatile Component of Rhizoma Chuanxiong, Confers Prophylaxis against Cerebral Ischemia via Nrf2 and HSP70 Signaling Pathways.
Z-Ligustilide (Z-LIG) is a major component in Rhizoma Chuanxiong, which has been traditionally used as a health food supplement for the prevention of cerebrovascular disease in China. This study investigates the ability of intranasal Z-LIG pretreatment to enhance protection against neuronal damage in rats with middle cerebral artery occlusion (MCAO) and the role of cellular stress response mechanisms Nrf2 and HSP70. Z-LIG significantly mitigated infarct volume, neurological dysfunction, blood-brain barrier disruption, and brain edema (p < 0.01). Moreover, Z-LIG prevented the loss of collagen IV, occludin, and ZO-1 (p < 0.05) and decreased MMP-2 and -9 levels (p < 0.01). Meanwhile, Z-LIG up-regulated NQO1 and HSP70. Notably, blockage of Nrf2-driven transcription or down-regulation of HSP70 remarkably attenuated the preventive effect of Z-LIG (p < 0.05). Together, intranasal delivery of Z-LIG enhanced protection against ischemic injury via Nrf2 and HSP70 signaling pathways and has prophylactic potential in the population at high risk of stroke.
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Juan
J
Li
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Jie
J
Yu
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Hui
H
Ma
Institute of Laboratory Animals, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital , Chengdu 610212, Sichuan, China.
Na
N
Yang
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Li
L
Li
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Ding-Ding
DD
Zheng
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Ming-Xia
MX
Wu
Institute of Laboratory Animals, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital , Chengdu 610212, Sichuan, China.
Zhi-Long
ZL
Zhao
College of Pharmaceutical Sciences, Southwest University , 2 Tiansheng Road, Beibei District, Chongqing 400716, China.
Hong-Yi
http://orcid.org/0000-0003-0564-3892
HY
Qi
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*
D004365:Drugs, Chinese Herbal; D018840:HSP70 Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C027820:ligustilide; D015107:4-Butyrolactone
HSP70; Nrf2; Z-ligustilide; intranasal delivery; ischemic stroke