Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation

• Published in: International journal of molecular sciences Vol. 23; no. 7; p. 4004
• Main Authors: Kim, So-Ra, Seong, Kyung-Joo, Kim, Won-Jae, Jung, Ji-Yeon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04-04-2022; MDPI
• Subjects: Alzheimer's disease; Antioxidants; Apoptosis; Caspase-3; Catechin - analogs & derivatives; Catechin - pharmacology; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Cytotoxicity; Encephalopathy; Epigallocatechin gallate; GA-binding protein; Humans; Hypoxia; Hypoxia, Brain - metabolism; Hypoxia-inducible factor 1a; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 6; Interleukin-6 - metabolism; Kinases; Lipopolysaccharides; Microglia; Microglia - metabolism; Neonates; NF-kappa B - metabolism; NF-κB; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Poly(ADP-ribose) polymerase; Polyphenols; Prostaglandin endoperoxide synthase; Proteins; Reactive Oxygen Species - metabolism; Ribose; Tea; Traumatic brain injury; Tumor necrosis factor-TNF; NF-κB; hypoxia; epigallocatechin gallate; inflammation; microglia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23074004

Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl
to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl
caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl
. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway.