Hydroxysafflor Yellow A Inhibits TNF-α-Induced Inflammation of Human Fetal Lung Fibroblasts via NF-κB Signaling Pathway

Abstract

Objective. Hydroxysafflor yellow A (HSYA), an effective ingredient of the Chinese herb Carthamus tinctorius L, attenuated bleomycin-induced pulmonary fibrosis in mice. This study is to investigate the effect of HSYA on the proliferation and inflammatory level of human fetal lung fibroblasts (MRC-5 cells) induced by tumor necrosis factor-α (TNF-α) and explore the underlying mechanisms. Methods. MRC-5 cells were treated with different concentrations of TNF-α, HSYA, or/and etanercept (ENCP, TNF-α receptor (TNFR1) antagonist, 500 ng/mL) before cell proliferation was detected. The laser confocal microscope was used to observe the role of HSYA in binding of TNF-α and its receptor. Co-immunoprecipitation was used to detect the binding of TNFR1 and TAK1-TAB2 complex. Real-time quantitative RT-PCR and western blot were used to detect the expressions of inflammation-related cytokines and proteins related with the NF-κB pathway. Luciferase reporter gene assay and chromatin coprecipitation method were used to detect the interaction between AP-1 and TGF-β1 promoter. Results. TNF-α (5 ng/mL) was used to induce inflammation and proliferation in MRC-5 cells. HSYA can partially suppress the stimulation of TNF-α on proliferation and inflammatory response of MRC-5 cells. HSYA could compete with TNF-α to bind with TNFR1 and hamper the binding of TNFR1 to TAK1-TAB2 complex. In addition, HSYA could also inhibit the activation of the NF-κB signal pathway and suppress the binding of TGF-β1 promoter with AP-1. Conclusion. Evidence in this study suggested that HSYA affects TNF-α-induced proliferation and inflammatory response of MRC-5 cells through the NF-κB/AP-1 signaling pathway, which may provide theoretical basis for HSYA treatment in pulmonary fibrosis.

Intense Pulsed Light Attenuates UV-Induced Hyperimmune Response and Pigmentation in Human Skin Cells

“…Although green IPL did not demonstrate considerable efficacy against the UVB-induced immune response, combined treatment with yellow and green IPL resulted in additional suppression of hyperimmune responses ( Figure 2 and Figure 3 ). This effect may have been due to the fact that yellow IPL has direct inhibitory effects on skin cell inflammation that differ from those of green IPL [ 13 , 14 ] and to the possibility that IPL may improve the responsiveness of several photoreceptors that react to green light [ 32 , 33 , 34 , 35 , 36 ]. Our findings provide remarkable insight into capable therapies for UVB-induced skin hyperimmunity.…”

“…Given these advantages of IPL treatment, we investigated whether IPL therapy can attenuate UVB-induced aging stress related to hyperimmune reactions and hyperpigmentation in human skin cells. Yellow light attenuates excessive inflammatory reactions in vitro and in vivo, including in humans [ 13 , 14 , 15 ]. It has also been reported that green light ameliorates pigmented lesions and reduces postlaser pigmentation [ 16 , 17 , 18 ].…”

Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization

“…Safflower, the tubular flower of Carthamus tinctorius , has been shown to promote blood circulation, remove blood stasis, and has been used to treat conditions such as diabetes-related cardiovascular diseases and diabetes-related CKD [ 23 , 24 ]. From a modern pharmacological perspective, the activity of safflower is related to its main compounds: Ka and HSYA [ 25 , 26 ].…”

A Metabolic Perspective and Opportunities in Pharmacologically Important Safflower

“…Several studies revealed that flower extract/compounds of hydroxysafflor yellows A and B (HSYA and HSYB) elicit various inflammatory responses, including proliferation and inflammatory responses of human fetal lung fibroblasts (MRC-5 cells) [57], inhibition of platelet activating factor (PAF)-induced proliferation, and an asthma-related inflammatory response in human bronchial smooth muscle cells (HBSMCs) [58]. In vivo studies showed that direct administration of HSYA (50, 75, and 112.5 mg/kg) to guinea pigs enhanced the protective effect on ovalbumin (OVA)-induced asthma, playing a role in controlling the asthma [59].…”