title: Allicin protects spinal cord neurons from glutamate-induced oxidative stress through regulating the heat shock protein 70/inducible nitric oxide synthase pathway.
abstract: Allicin, the main biologically active compound derived from garlic, exerts a broad spectrum of pharmacological activities and is considered to have therapeutic potential in many neurological disorders. Using an in vitro spinal cord injury model induced by glutamate treatment, we sought to investigate the neuroprotective effects of allicin in primary cultured spinal cord neurons. We found that allicin treatment significantly attenuated glutamate-induced lactate dehydrogenase (LDH) release, loss of cell viability and apoptotic neuronal death. This protection was associated with reduced oxidative stress, as evidenced by decreased reactive oxygen species (ROS) generation, reduced lipid peroxidation and preservation of antioxidant enzyme activities. The results of western blot analysis showed that allicin decreased the expression of inducible nitric oxide synthase (iNOS), but had no effects on the expression of neuronal NOS (nNOS) following glutamate exposure. Moreover, allicin treatment significantly increased the expression of heat shock protein 70 (HSP70) at both mRNA and protein levels. Knockdown of HSP70 by specific targeted small interfere RNA (siRNA) not only mitigated allicin-induced protective activity, but also partially nullified its effects on the regulation of iNOS. Collectively, these data demonstrate that allicin treatment may be an effective therapeutic strategy for spinal cord injury, and that the potential underlying mechanism involves HSP70/iNOS pathway-mediated inhibition of oxidative stress.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China. hexijing_xjtu@163.com.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Liu
authors.forename: Peng-Yu
authors.initials: PY
authors.lastname: Ren
authors.forename: Guo-Yu
authors.initials: GY
authors.lastname: Wang
authors.forename: Shu-Xin
authors.initials: SX
authors.lastname: Yao
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: He
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004220:Disulfides; D004622:Embryo, Mammalian / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000506:poisoning; D018840:HSP70 Heat-Shock Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D064209:Phytochemicals / Q000494:pharmacology*; D034622:RNA Interference; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013441:Sulfinic Acids / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004220:Disulfides; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D064209:Phytochemicals; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids; C006452:allicin; D018698:Glutamic Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat