2,3,4',5-tetrahydroxystilbene-2-O-β-d-glucoside exerts anti-inflammatory effects on lipopolysaccharide-stimulated microglia by inhibiting NF-κB and activating AMPK/Nrf2 pathways.
2,3,4',5-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) affects neuroinflammation-related neurodegenerative diseases and inhibits neuroinflammatory mediators. However, the detailed impacts and underlying mechanisms of THSG on neuroinflammatory responses are still unclear. The aim of this study was to investigate the anti-neuroinflammatory mechanism of THSG via AMPK/Nrf2 signaling pathways. This study showed that THSG attenuated LPS-induced iNOS, COX-2, TNF-α, and IL-6 activation in microglia. Furthermore, it was observed that activation of IκBα and NF-κB was significantly increased upon LPS stimulation, and suppressed by THSG treatment in a dose-dependent manner. The expression of HO-1 and NQO1, as well as Nrf2 activation, was induced by THSG in microglia. The promoter activity of ARE and HO-1 also increased in a dose-dependent manner following THSG treatment. Nrf2/HO-1/NQO1 has anti-inflammatory properties; the knock-down of Nrf2/HO-1/NQO1 by specific siRNA prevented the THSG-mediated inhibition of iNOS and COX-2 promoter activity. Consistent with this concept, the phosphorylation of LKB1, CaMKII, and AMPK were elevated after THSG treatment. The blockade of AMPK by a pharmacological inhibitor prevented THSG-induced HO-1 and NQO1 expression. The anti-inflammatory properties of THSG were also reversed by treatment with an AMPK inhibitor. In conclusion, we demonstrated that THSG attenuates the LPS-induced neuroinflammatory response mediated by AMPK/Nrf2 signaling pathways.
Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
Sun Young
SY
Park
Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
Mei Ling
ML
Jin
Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, Republic of Korea.
Ziyu
Z
Wang
Department of Nanomaterials Engineering, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: gtpark@pusan.ac.kr.
Geuntae
G
Park
Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, Republic of Korea. Electronic address: ywchoi@pusan.ac.kr.
Young-Whan
YW
Choi
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005960:Glucosides; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D012333:RNA, Messenger; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D009569:Nitric Oxide; D055372:AMP-Activated Protein Kinases
AMPK; Anti-Neuroinflammation; Microglia; Nrf2; THSG