Andrographolide Protects against HG-Induced Inflammation, Apoptosis, Migration, and Impairment of Angiogenesis via PI3K/AKT-eNOS Signalling in HUVECs

• Published in: Mediators of inflammation Vol. 2019; no. 2019; pp. 1 - 15
• Main Authors: Tang, Qi-Zhu, Xiao, Yang, Liu, Chen, Wu, Qing-Qing, Zhou, Heng, Duan, Ming-Xia, Deng, Wei
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2019; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Angiogenesis; Apoptosis; Apoptosis - drug effects; Bioengineering; Blotting, Western; Cardiomyopathy; Cell adhesion & migration; Cell cycle; Cell growth; Cell migration; Cell Movement - drug effects; Diabetes; Disease; Diterpenes - pharmacology; Endothelium; Gene expression; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; IL-1β; Immunofluorescence; In Situ Nick-End Labeling; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - prevention & control; Interleukin 6; Kinases; L-Lactate Dehydrogenase - metabolism; Malondialdehyde - metabolism; NG-Nitroarginine methyl ester; Nitric Oxide Synthase Type III - metabolism; Oncology; Oxidative stress; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Toxicology; Tumor necrosis factor-α; Vascular endothelial growth factor; China; United States > US; Germany
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2019/6168340

Andrographolide (Andr) is a major component isolated from the plant Andrographis paniculata. Inflammation, apoptosis, and impaired angiogenesis are implicated in the pathogenesis of high glucose (HG)-induced injury of vascular endotheliocytes. Our study is aimed at evaluating the effect of Andr on HG-induced HUVEC injury and the underlying mechanism. HUVECs were exposed to HG levels (33 mM) and treated with Andr (0, 12.5, 25, and 50 μM). Western blot analysis, real-time PCR, immunofluorescence staining, the scratch test, and the tube formation assay were performed to assess the effects of Andr. We discovered that Andr inhibited the inflammatory response (IL-1β, IL-6, and TNFα), decreased the apoptosis ratio and cell migration, and promoted tube formation in response to HG stimulation. Andr ameliorated the levels of phosphorylated PI3K (p-PI3K), phosphorylated AKT (p-AKT), and phosphorylated eNOS (p-eNOS). The expression of vascular endothelial growth factor (VEGF) protein, a vital factor in angiogenesis, was improved by Andr treatment under HG stimulation. LY294002 is a blocker of PI3K, MK-2206 2HCI (MK-2206) is a highly selective AKT inhibitor, and L-NAME is a suppressor of eNOS, all of which significantly reduce Andr-mediated protective effects in vitro. Hence, Andr may be involved in regulating HG-induced injury by activating PI3K/AKT-eNOS signalling in HUVECs.