Post-injury administration of allicin attenuates ischemic brain injury through sphingosine kinase 2: In vivo and in vitro studies.
Allicin, one of the main biologically active compounds derived from garlic, has been shown to exert various pharmacological activities and is considered to have therapeutic potential for many pathologic conditions. In the present study, we investigated the potential post-ischemic neuroprotective effects of allicin and its underlying mechanisms. Using a rat middle cerebral artery occlusion (MCAO) model, we found that intraperitoneal treatment with 50 mg/kg allicin significantly reduced brain infarct volume, attenuated cerebral edema and decreased the neurological deficit score. Allicin treatment also diminished TUNEL positive cells and inhibited the activation of caspase-3 after MCAO. These protective effects could be observed even if the administration was delayed to 6 h after injury. In addition, we evaluated the in vitro protective effects of allicin against oxygen glucose deprivation (OGD) induced neuronal injury in primary cultured cortical neurons. Allicin (50 μM) increased neuronal viability, decreased lactate dehydrogenase (LDH) release and inhibited apoptotic neuronal death after OGD. These protective effects could be observed even if the administration was delayed to 4 h after injury. Furthermore, allicin significantly increased the expression of sphingosine kinases 2 (Sphk2) both in vivo and in vitro. Pretreatment with the Sphk2 inhibitor ABC294640 partially reversed the protective effects of allicin against MCAO and OGD injury, indicating that an Sphk2-mediated mechanism was involved in allicin-induced protection in our models. The combination of findings suggests that post-injury administration of allicin has potential as a neuroprotective strategy for ischemic stroke.
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China.
Jia-Ji
JJ
Lin
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China.
Ting
T
Chang
Department of Cardio-Thoracic Surgery, Kunming General Hospital of Chengdu Military Region, Kunming, Yunnan, 650000, China.
Wen-Ke
WK
Cai
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China.
Zhuo
Z
Zhang
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China.
Yong-Xiang
YX
Yang
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China.
Chao
C
Sun
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China. Electronic address: fmmulizhuyi@126.com.
Zhu-Yi
ZY
Li
Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi, 710004, China. Electronic address: fmmuliweixin@126.com.
Wei-Xin
WX
Li
D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000517:prevention & control*; D002545:Brain Ischemia / Q000201:enzymology* / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004220:Disulfides; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013441:Sulfinic Acids / Q000008:administration & dosage*; D000099157:Sphingosine Kinase
D004220:Disulfides; D017853:Phosphotransferases (Alcohol Group Acceptor); D013441:Sulfinic Acids; D000099157:Sphingosine Kinase; C006452:allicin
Allicin; Apoptosis; Ischemic brain injury; OGD; Sphingosine kinase