title: Ginsenoside Rg1 suppressed inflammation and neuron apoptosis by activating PPARγ/HO-1 in hippocampus in rat model of cerebral ischemia-reperfusion injury.
abstract: Generally accepted, inflammation and neuron apoptosis are two characterized pathological features of cerebral ischemia-reperfusion (IR) injury. Ginsenoside Rg1 was reported showing distinct neuroprotective effect in cerebral IR injury but the underlying mechanisms are still unclear. PPARγ/Heme oxygenase-1 (HO-1) signaling was proved effective in suppressing both apoptosis and inflammation. This study was aimed to investigate whether PPARγ/HO-1 signaling was involved in cerebral IR injury and ginsenoside Rg1's neuroprotective effect in cerebral IR injury. Cerebral IR injury was induced by middle cerebral artery occlusion in rats. The PPARγ agonist rosiglitazone (ROZ) and the HO-1 inhibitor zinc protoporphyrin-IX (ZnPP) and ginsenoside Rg1 at various concentrations were used to treat the modeled rats. Neurological deficits, apoptosis and inflammation in hippocampus were evaluated. Furthermore, HO-1 enzymatic activity, expression levels of apoptosis-related and inflammation-related proteins, concentrations of inflammatory cytokines were also determined. The results showed that PPARγ activation by ROZ significantly attenuated neurological deficits, apoptosis and inflammation in hippocampus in cerebral IR rats. However, the neuroprotective effect of ROZ was then impaired by HO-1 inhibitor ZnPP. This effect was evidenced by changes of expression levels of PPARγ, bcl-2, cleaved caspase-3, cleaved caspase-9, IL-1β, TNF-α, HMGB1, and RAGE in hippocampus of modeled animals. Ginsenoside Rg1 showed similar effect to ROZ in activating PPARγ/HO-1 in protecting against apoptosis and inflammation but also impaired by ZnPP administration. In conclusion, PPARγ/HO-1 signaling was critical in mediating apoptosis and inflammation, which was also the therapeutic target of ginsenoside Rg1 in cerebral IR injury.
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
authors.forename: Yuandong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
authors.forename: Lingmin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Jing
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China ; Department of Surgery, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D036145:Ginsenosides / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D036145:Ginsenosides; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D047495:PPAR gamma; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C035054:ginsenoside Rg1
keywords: Cerebral ischemia-reperfusion injury; PPARγ; apoptosis; inflammation