Tectorigenin attenuates the OGD/R-induced HT-22 cell damage through regulation of the PI3K/AKT and the PPARγ/NF-κB pathways

• Published in: Human & experimental toxicology Vol. 40; no. 8; pp. 1320 - 1331
• Main Authors: Yao, Li, Yang, Meili, Zhang, Juanli, Wang, Fei, Liu, Qing, Xie, Xiaojun, Liu, Zhuo, Guo, Qiang, Su, Hang, Zhai, Jiemin, He, Jianbo, Xue, Sha, Qiu, Zhengguo
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.08.2021; Sage Publications Ltd
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Anti-Inflammatory Agents - pharmacology; Anticancer properties; Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Brain injury; Cell Hypoxia; Cell Line; Cell survival; Cell Survival - drug effects; Cytokines; Cytokines - genetics; Cytokines - metabolism; Damage; Deprivation; Glucose; Glucose - deficiency; Head injuries; IL-1β; Inflammation; Inhibitors; Interleukin 6; Ischemia; Isoflavones - pharmacology; Lipopolysaccharides; Mice; Neuroprotective Agents - pharmacology; NF-kappa B - metabolism; NF-κB protein; Oxidants; Oxidative Stress - drug effects; Oxidizing agents; Oxygen; Phosphatidylinositol 3-Kinases - metabolism; PPAR gamma - genetics; PPAR gamma - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Reperfusion; Signal Transduction - drug effects; Survival; Tumor necrosis factor-α; traditional Chinese medicine; apoptosis; Cerebral ischemia-reperfusion injury; inflammation; ROS production
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327121993213

Tectorigenin (TEC) is an effective compound that derived from many plants, such as Iris unguicularis, Belamcanda chinensis and Pueraria thunbergiana Benth. Evidence suggested that TEC has anti-tumor, anti-oxidant activity, anti-bacterial and anti-inflammatory effects. In addition, there has some evidence indicated that TEC is a potential anti-stroke compound; however, its specific roles and associated mechanism have not yet been elucidated. In the present study, we aimed to investigate the anti-inflammatory, anti-oxidant activity and anti-apoptosis effects of TEC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT-22 cells, and clarified the relevant mechanisms. Here, we observed that TEC significantly promoted cell survival, impeded cell apoptosis, inhibited ROS and inflammatory cytokines IL-1β, IL-6, TNF-α production in OGD/R-induced HT-22 cells. Moreover, TEC activated PI3K/AKT signal pathway, increased PPARγ expression and inhibited NF-κB pathway activation in OGD/R-induced HT-22 cells. Further studies indicated that PPARγ inhibitor GW9662 activated NF-κB pathway after TEC treatment in OGD/R-induced HT-22 cells. Also, PI3K/AKT inhibitor LY294002, PPARγ inhibitor GW9662 and NF-κB activator LPS both reversed the effects of TEC on OGD/R-induced HT-22 cell biology. Taken together, this research confirmed that TEC benefit to HT-22 cell survival and against OGD/R damage through the PI3K/AKT and PPARγ/NF-κB pathways. These results indicated that TEC might be an effective compound in the treatment for ischemic brain injury.