title: Hydroxy-safflor yellow A inhibits neuroinflammation mediated by Aβ₁₋₄₂ in BV-2 cells.
abstract: Inflammation is an important contributor to the development of Alzheimer's disease (AD). Anti-inflammatory medication may offer promising treatment for AD. Hydroxy-safflor yellow A (HSYA), a chemical component of the safflower yellow pigments, has been reported to exert potent immunosuppressive effects. This study examined the anti-inflammatory effects of HSYA in Aβ₁₋₄₂-treated BV-2 microglia cells. The mRNA levels of IL-1β, IL-4, IL-10, TNF-α, COX-2 and iNOS were detected by real-time PCR. Western blotting was used to determine the protein expression of COX-2, TNF-α, iNOS, Janus Kinase 2 (JAK2), p-JAK2, signal transducers and activators of transcription 3 (STAT3) and p-STAT3. BV2-conditioned medium was used to treat SH-SY5Y cells and primary neuronal cells in indirect toxicity experiments. Cell viability and apoptosis were assessed using MTT assay and Annexin V/PI staining respectively. The results demonstrated that HSYA significantly reduced the expression of the pro-inflammatory mediators and inhibited Aβ₁₋₄₂-induced neuroinflammation. Moreover, HSYA protected primary cortical neurons and SH-SY5Y cells against microglia-mediated neurotoxicity. HSYA also enhanced the phosphorylation of JAK2/STAT3 pathway and inhibition of JAK2 by AG 490 attenuated the anti-inflammatory effects of HSYA. Overall, our findings suggested that HSYA inhibited Aβ₁₋₄₂-induced inflammation and conferred neuroprotection partially through JAK2/STAT3 pathway, indicating that HSYA could be a potential drug for the treatment of AD.
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: Zuohui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
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: Xinchen
authors.initials: X
authors.lastname: Hui
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
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; 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 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone
keywords: Beta-amyloid; Hydroxy-safflor yellow A; Inflammation; Microglia; STAT