title: Hydroxy-safflor yellow A attenuates Aβ₁₋₄₂-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway.
abstract: Beta-amyloid (Aβ)-mediated inflammation plays a critical role in the initiation and progression of Alzheimer׳s disease (AD). Anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of hydroxy-safflor yellow A (HSYA) on Aβ1-42-induced inflammation in AD mice was investigated and the underlying mechanisms were explored. Aβ1-42 was injected into bilateral hippocampi of mice to induce AD models in vivo. Spatial learning and memory of mice were investigated by the Morris water maze test. Activated microglia and astrocytes were examined by immunofluorescence staining for ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). The mRNA of inflammatory cytokines were measured using real-time PCR. NF-κB p65 translocation was analyzed by western blotting and immunostaining. IκB and phosphorylation of JAK2 and STAT3 were tested by western blotting. The results showed that HSYA ameliorated the memory deficits in Aβ1-42-induced AD mice. HSYA suppressed Aβ1-42-induced activation of microglia and astrocytes and reduced the mRNA expression of pro-inflammatory mediators. HSYA up-regulated the JAK2/STAT3 pathway and inhibits the activation of NF-κB signaling pathways. Pharmacological inhibition of STAT3 by AG490 reversed the inactivation of p65 and anti-inflammatory effects of HSYA. In conclusion, these results suggest that HSYA protects Aβ1-42-induced AD model through inhibiting inflammatory response, which may involve the JAK2/STAT3/NF-κB pathway.
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China; Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221006, PR China.
authors.forename: Zuo-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Lin-Jie
authors.initials: LJ
authors.lastname: Yu
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China; School of Clinical Medicine, South East University, Nanjing, Jiangsu 210008, PR China.
authors.forename: Xin-Chen
authors.initials: XC
authors.lastname: Hui
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Yin
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China; Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China; School of Clinical Medicine, South East University, Nanjing, Jiangsu 210008, PR China; Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing, Jiangsu 210008, PR China. Electronic address: xuyun20042001@aliyun.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D011809:Quinones / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D016328:NF-kappa B; D010446:Peptide Fragments; D011809:Quinones; D050796:STAT3 Transcription Factor; C075222:amyloid beta-protein (1-42); C085278:hydroxysafflor yellow A; D002599:Chalcone; D053614:Janus Kinase 2
keywords: Alzheimer׳s disease; Beta-amyloid; Hydroxy-safflor yellow A; Inflammation; JAK2/STAT3; NF-κB pathway