title: Tetramethyl Pyrazine Protects Hippocampal Neurons Against Anoxia/Reoxygenation Injury Through Inhibiting Apoptosis Mediated by JNK/MARK Signal Pathway.
abstract: BACKGROUND Tetramethyl pyrazine (TMP) is a typical biologically active alkaloid isolated from the Chinese herb Ligusticum walliichi. It has been reported that TMP shows neuroprotective and stroke injury reductive properties in cerebral ischemia/reperfusion (I/R) animal models. In the present study we sought to investigate the effect and potential intervention mechanism of TMP in anoxia/reoxygenation (A/R) rat hippocampal neurons. MATERIAL AND METHODS After being cultured for 7 days, primary hippocampal neurons were randomly assigned into a normal control group (N), a TMP group (C: 0 ug/ml, L: 60 ug/ml, M: 200ug/ml and H: 800 ug/ml), and a JNK inhibitor group (S: SP600125, 10 μmol/L). A hypoxia/reoxygenation model were prepared 1 h after incubation. Hippocampal neurons were incubated in 90% N2 and 10% CO2 for 2 h, and then reoxygenated for 24 h in an incubator with 5%CO2 at the temperature of 37°C. The apoptosis rate, MKK4 and MKK7 mRNA and JNK kinase protein levels (C-fos, c-jun, and P-JNK) of hippocampal neurons were detected. RESULTS The apoptosis rates of hippocampal neurons induced by A/R showed significant reduction after being pre-treated with JNK inhibitor, TMP 60 µg/ml, 200 µg/ml, and 800 µg/ml. The JNK kinase MKK4mRNA and MKK7mRNA levels, as well as the expressions of C-fos, C-jun, and P-JNK protein levels, were also be reduced. CONCLUSIONS TMP may produce a protective effect in anoxia/reoxygenation-induced primary hippocampal neuronal injury by inhibiting the apoptosis of the hippocampal neurons; the possible mechanism may be inhibition of the JNK signal pathway.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (mainland).
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (mainland).
authors.forename: Wuhua
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (mainland).
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (mainland).
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China (mainland).
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D006624:Hippocampus / Q000473:pathology; D000860:Hypoxia / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D000873:Anthracenes; D018696:Neuroprotective Agents; D011719:Pyrazines; D012333:RNA, Messenger; C432165:pyrazolanthrone; D020929:Mitogen-Activated Protein Kinase Kinases; D010100:Oxygen; C017953:tetramethylpyrazine