hydroxysafflor-yellow-a and Acute-Lung-Injury

To investigate the protective effect of hydroxysafflor yellow A (HSYA) against heat stroke (HS)-induced acute lung injury and its possible mechanism.. HSYA pretreatment at the moderate and high doses significantly improved heat tolerance of the mice with comparable effects. At the optimal dose of 2.25 mg/kg, HSYA pretreatment significantly increased heat tolerance of the mice (. Severe HS results in necroptosis in the lung tissue of mice, which can be alleviated by HSYA pretreatment.

Topics: Acute Lung Injury; Animals; Heat Stroke; HMGB1 Protein; Interleukin-6; Mice; Mice, Inbred C57BL; Necroptosis; Tumor Necrosis Factor-alpha

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.

Topics: Acute Lung Injury; Carthamus tinctorius; Chalcone; Extracellular Signal-Regulated MAP Kinases; Extracellular Traps; HL-60 Cells; Humans; Lipopolysaccharides; Pigments, Biological; Quinones; Tetradecanoylphorbol Acetate

Hydroxysafflor yellow A (HSYA) is a main bio-active compound important of a traditional Chinese medicine named Carthamus tinctorius L. and has been shown to possess various effects, especially anti-inflammatory benefits and potential protections against acute lung injury (ALI) in previous studies. Therefore, in this present study, we aimed to evaluating effects of HSYA on lipopolysaccharide (LPS)-induced ALI in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results demonstrated that HSYA abated LPS-induced pathological change and attenuated lung vascular permeability and edema. HSYA down-regulated both the ability of myeloperoxidase (MPO) in lung tissues and levels of inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IFN(interferon)-β in serum. Moreover, HSYA prevented toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF) protein up-expressions. In addition, the activations of mitogen-activated protein kinases including p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) were blocked by HSYA. And also, the phosphorylations of interferon regulatory factor 3 (IRF3), translocation of nuclear factor kappa B (NF-κB)/p65 and inhibitory kappa B (IκB)-α were inhibited by HSYA. In conclusion, HSYA attenuated inflammatory response in ALI mice through inhibition of TLR 4-dependent signaling pathways.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Blotting, Western; Bronchoalveolar Lavage Fluid; Chalcone; Cytokines; Disease Models, Animal; Endotoxins; Enzyme-Linked Immunosorbent Assay; Male; Medicine, Chinese Traditional; Mice, Inbred ICR; Molecular Structure; Quinones; Signal Transduction; Toll-Like Receptor 4

Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO2), carbon dioxide tension, pH, and the PaO2/fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22(phox) levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI.

Topics: Acute Lung Injury; Animals; Chalcone; Cyclic AMP-Dependent Protein Kinases; Enzyme Activation; Male; Oleic Acid; Protein Kinase Inhibitors; Quinones; Random Allocation; Rats; Rats, Sprague-Dawley

Hydroxysafflor yellow A (HSYA) is an effective ingredient of Chinese herb Carthamus tinctorius L. The aim of this study was to evaluate the protective effect of HSYA on inflammatory phase of bleomycin-induced pulmonary injury in mice. Three doses of HSYA (26.7, 40, 60 mg/kg/d) were intraperitoneally injected to mice consecutively for 1 week after bleomycin administration. It was found that HSYA attenuated the loss in body weight, the increase of myeloperoxidase activity and pathologic changes of pulmonary inflammation caused by bleomycin. Treatment with HSYA also alleviated bleomycin-induced increase of mRNA level of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and transforming growth factor (TGF)-β1 in lung homogenates. Moreover HSYA inhibited the increased activation of nuclear factor (NF)-κB and phosphorylation of p38 mitogen-activated protein kinases (MAPK) in lung tissue. These findings demonstrated that HSYA had protective effect on bleomycin-induced lung inflammatory response.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bleomycin; Carthamus; Chalcone; Cytokines; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Peroxidase; Phytotherapy; Plant Extracts; Quinones; RNA, Messenger; Transcription Factor RelA

Hydroxysafflor yellow A (HSYA) is a component of the flower of Carthamus tinctorius L. The present study investigated whether HSYA could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) administration. Male Kunming mice were pretreated with HSYA 0.5 h prior to intraperitoneal application of LPS. Arterial blood gas, lung water content index, lung tissue myeloperoxidase (MPO) activity, mRNA expression of inflammatory cytokines, NF-κBp65, p38 mitogen-activated protein kinase (MAPK) and pathological changes in lung morphology were assessed. After LPS administration, all animals displayed increased arterial carbon dioxide partial pressure (PaCO₂), and decreased arterial oxygen partial pressure (PaO₂), arterial oxygen saturation (SO₂), HCO₃⁻ concentration and pH, which were ameliorated by pretreating the animals with HSYA. HSYA administration significantly attenuated inflammatory cell infiltration and alleviated pulmonary edema induced by LPS. Moreover, HSYA decreased NF-κB p65 nuclear translocation, inhibited proinflammatory cytokine TNF-α, IL-1β and IL-6 mRNA expression and promoted antiinflammatory cytokine IL-10 gene expression following LPS injection. Pulmonary p38 MAPK phosphorylation was upregulated 4 h after LPS treatment, which could be suppressed by pretreatment with HSYA. These findings demonstrated the protective effect of HSYA against LPS-induced acute lung injury, which is suggested to be associated with the inhibition of p38 MAPK, NF-κB p65 activation and alteration of inflammatory cytokine expression.

Topics: Acute Lung Injury; Animals; Blood Gas Analysis; Chalcone; Cytokines; Lipopolysaccharides; Lung; Male; Mice; p38 Mitogen-Activated Protein Kinases; Peroxidase; Quinones; Transcription Factor RelA

This study is to investigate the pharmacological effect and mechanism of action of hydroxysafflor yellow A (HSYA) on acute lung injury (ALI). The rat ALI was induced by oleic acid and lipopolysaccharide (LPS) injection. The incidence of acidosis, PaO2 (arterial blood oxygen pressure), W/D (wet weight/dry weight) and lung index (LI) were measured. Electron microscope and optical microscope were applied to observe lung morphological changes in rat. RT-PCR was used to determine TNF-alpha and ICAM-1 mRNA level. Inhibition effect of HSYA on plasma inflammatory cytokine expression was measured by ELISA. HSYA could alleviate pulmonary edema, reduce acidosis, keep PaO2 from descending, inhibit inflammatory cell infiltration, inhibit rat lung TNF-alpha and ICAM-1 mRNA expression and plasma IL-6 and IL-1beta level elevation. HSYA is an effective ingredient to remit ALI induced by oleic acid and LPS in rat.

Topics: Acute Lung Injury; Animals; Carthamus tinctorius; Chalcone; Flowers; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lung; Male; Oleic Acid; Plants, Medicinal; Quinones; Rats; Rats, Wistar; RNA, Messenger; Tumor Necrosis Factor-alpha