title: Hydroxysafflor Yellow A Attenuates Neuron Damage by Suppressing the Lipopolysaccharide-Induced TLR4 Pathway in Activated Microglial Cells.
abstract: Microglia activation initiates a neurological deficit cascade that contributes to substantial neuronal damage and impairment following ischemia stroke. Toll-like receptor 4 (TLR4) has been demonstrated to play a critical role in this cascade. In the current study, we tested the hypothesis that hydroxysafflor yellow A (HSYA), an active ingredient extracted from Flos Carthami tinctorii, alleviated inflammatory damage, and mediated neurotrophic effects in neurons by inducing the TLR4 pathway in microglia. A non-contact Transwell co-culture system comprised microglia and neurons was treated with HSYA followed by a 1 mg/mL lipopolysaccharide (LPS) stimulation. The microglia were activated prior to neuronal apoptosis, which were induced by increasing TLR4 expression in the activated microglia. However, HSYA suppressed TLR4 expression in the activated microglia, resulting in less neuronal damage at the early stage of LPS stimulation. Western blot analysis and immunofluorescence indicated that dose-dependently HSYA down-regulated TLR4-induced downstream effectors myeloid differentiation factor 88 (MyD88), nuclear factor kappa b (NF-κB), and the mitogen-activated protein kinases (MAPK)-regulated proteins c-Jun NH2-terminal protein kinase (JNK), protein kinase (ERK) 1/2 (ERK1/2), p38 MAPK (p38), as well as the LPS-induced inflammatory cytokine release. However, HSYA up-regulated brain-derived neurotrophic factor (BDNF) expression. Our data suggest that HSYA could exert neurotrophic and anti-inflammatory functions in response to LPS stimulation by inhibiting TLR4 pathway-mediated signaling.
authors.affiliation: Pharmacy Department, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang, 330006, China. lvyanni@126.com.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, 330001, China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Pharmacy Department, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang, 330006, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Ou-Yang
authors.affiliation: Pharmacy Department, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang, 330006, China.
authors.forename: Longsheng
authors.initials: L
authors.lastname: Fu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D021381:Protein Transport; D011809:Quinones / Q000494:pharmacology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018696:Neuroprotective Agents; D011809:Quinones; C498144:Rela protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C085278:hydroxysafflor yellow A; D002599:Chalcone; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Anti-inflammatory; Co-culture system; Hydroxysafflor yellow A; Microglia; Neurons; Neuroprotective effect; Neurotrophic; Toll-like receptor 4