Baicalin alleviates hyperglycemia-induced endothelial impairment via Nrf2
Autor: | Litai Jin, Gen Chen, Jia Sun, Weitao Cong, Xiangjuan Chen, Ning An, Santie Li, Weijian Ye, Huang Xiaozhong, Jiaojiao Liang, Shuai Huang, Chao Niu, Yingjie Shen |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
chemistry.chemical_classification medicine.medical_specialty Reactive oxygen species Angiogenesis Chemistry Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism medicine.disease Streptozotocin medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology Internal medicine medicine Endothelial dysfunction Protein kinase B Baicalin PI3K/AKT/mTOR pathway Oxidative stress medicine.drug |
Zdroj: | Journal of Endocrinology. 240:81-98 |
ISSN: | 1479-6805 0022-0795 |
Popis: | Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine, which exhibits strong anti-inflammatory, anti-viral and anti-tumor activities. The present work was devoted to elucidate the molecular and cellular mechanisms underlying the protective effects of Baicalin against diabetes-induced oxidative damage, inflammation and endothelial dysfunction. Diabetic mice, induced by streptozotocin (STZ), were treated with intraperitoneal Baicalin injections. Human umbilical vein endothelial cells (HUVECs) were cultured either in normal glucose (NG, 5.5 mM) or high glucose (HG, 33 mM) medium in the presence or absence of Baicalin for 72 h. We observed an obvious inhibition of hyperglycemia-triggered oxidative damage and inflammation in HUVECs and diabetic aortal vasculature by Baicalin, along with restoration of hyperglycemia-impaired nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway activity. However, the protective effects of Baicalin almost completely abolished in HUVECs transduced with shRNA against Nrf2, but not with nonsense shRNA. Mechanistic studies demonstrated that HG decreased Akt and GSK3B phosphorylation, restrained nuclear export of Fyn and nuclear localization of Nrf2, blunted Nrf2 downstream target genes and subsequently induced oxidative stress in HUVECs. However, those destructive cascades were well prevented by Baicalin in HUVECs. Furthermore, LY294002 and ML385 (inhibitor of PI3K and Nrf2) attenuated Baicalin-mediated Nrf2 activation and the ability of facilitates angiogenesis in vivo and ex vivo. Taken together, the endothelial protective effect of Baicalin under hyperglycemia condition could be partly attributed to its role in downregulating reactive oxygen species (ROS) and inflammation via the Akt/GSK3B/Fyn-mediated Nrf2 activation. |
Databáze: | OpenAIRE |
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