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Published on: October 25, 2016
Hydroxysafflor Yellow A Attenuates Neuron Damage by Suppressing the Lipopolysaccharide-Induced TLR4 Pathway in
Yanni Lv1, Yisong Qian2, Aijun Ou-Yang3
1Pharmacy Department, The First Affiliated Hospital of Nanchang University, Yongwai Street 17, Nanchang, 330006, China. lvyanni@126.com.
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.
Insights
Hydroxysafflor yellow A (HSYA) reduces neuroinflammation and neuronal damage after stroke by inhibiting the Toll-like receptor 4 (TLR4) pathway in microglia. It also promotes neurotrophic effects, offering potential therapeutic benefits.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Microglia activation drives neurological deficits post-ischemic stroke.
- Toll-like receptor 4 (TLR4) is a key mediator in this inflammatory cascade.
- Hydroxysafflor yellow A (HSYA) is investigated for its potential neuroprotective properties.
Purpose of the Study:
- To investigate if HSYA alleviates inflammatory damage and mediates neurotrophic effects in neurons by modulating the TLR4 pathway in microglia.
- To test the hypothesis that HSYA inhibits TLR4-induced inflammatory responses and promotes neuronal survival.
Main Methods:
- Utilized a Transwell co-culture system of microglia and neurons.
- Stimulated cells with lipopolysaccharide (LPS) and treated with varying doses of HSYA.
- Assessed TLR4 expression, downstream signaling molecules (MyD88, NF-κB, MAPK pathway), inflammatory cytokine release, and brain-derived neurotrophic factor (BDNF) expression via Western blot and immunofluorescence.
Main Results:
- HSYA suppressed LPS-induced TLR4 expression in activated microglia.
- HSYA dose-dependently down-regulated TLR4 downstream effectors (MyD88, NF-κB, JNK, ERK1/2, p38) and reduced inflammatory cytokine release.
- HSYA significantly up-regulated brain-derived neurotrophic factor (BDNF) expression.
Conclusions:
- HSYA exhibits anti-inflammatory effects by inhibiting the TLR4 signaling pathway in microglia.
- HSYA demonstrates neurotrophic properties, potentially by up-regulating BDNF.
- HSYA shows promise as a therapeutic agent for mitigating neuroinflammation and neuronal damage in ischemic stroke.
