title: Tetrandrine protects against oxygen-glucose-serum deprivation/reoxygenation-induced injury via PI3K/AKT/NF-κB signaling pathway in rat spinal cord astrocytes.
abstract: Tetrandrine (TET) is a bis-benzylisoquinoline alkaloid, which is isolated from a Chinese medicinal herb with antioxidant and anti-inflammatory activities. In this study, we investigated the effects of TET on oxygen-glucose-serum deprivation/reoxygenation (OGSD/R)-induced injury in rat spinal cord astrocytes, which mimics hypoxic/ischemic conditions in vivo. MTT and LDH assays indicated that cell viability was distinctly reduced and LDH leakage was elevated after OGSD/R exposure, which were dose-dependently reversed by pretreatment with TET (0.1, 1, 10, 20μM). Western blot analysis showed that OGSD/R exposure resulted in an enhanced expression of Bax and Caspase-3 proteins, and Bcl-2 reduction; whereas these effects were dose-dependently restored by TET pretreatment. TET pretreatment also dose-dependently inhibited the elevated Caspase-3 activity in OGSD/R-treated astrocytes. The oxidative stress status was evaluated using commercial kits, and the results demonstrated that OGSD/R exposure induced obvious oxidative stress, accompanied by elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reduced superoxide dismutase (SOD) activity, which were dose-dependently restored by TET pretreatment. In addition, TET pretreatment diminished the accumulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) induced by OGSD/R. Moreover, TET pretreatment dose-dependently suppressed Akt phosphorylation and nuclear factor-kappaB (NF-κB) activity augmented by OGSD/R. Similarly, both PI3K inhibitor LY294002 and NF-κB inhibitor PDTC notably attenuated OGSD/R-induced Akt phosphorylation, NF-κB activation, ROS generation, and TNF-α secretion. Taken together, these data demonstrated that TET protected against OGSD/R-induced injury in rat spinal cord astrocytes, which may be attributed to its antioxidant and anti-inflammatory activities via PI3K/AKT/NF-κB signaling pathway.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China. Electronic address: baogang1973@aliyun.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China.
authors.forename: Chuankun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, PR China.
authors.forename: Baixiang
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000473:pathology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D007249:Inflammation / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D044182:Benzylisoquinolines; D016328:NF-kappa B; D018696:Neuroprotective Agents; C009438:tetrandrine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D010100:Oxygen
keywords: Inflammatory response; Oxidative stress; Oxygen-glucose-serum deprivation/reoxygenation; Spinal cord astrocytes; Tetrandrine