Hydroxysafflor yellow A suppresses oleic acid-induced acute lung injury via protein kinase A.
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.
School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003, PR China.
Chaoyun
C
Wang
Qingxian
Q
Huang
Chunhua
C
Wang
Xiaoxi
X
Zhu
Yunfeng
Y
Duan
Shuai
S
Yuan
Xianyong
X
Bai
D055371:Acute Lung Injury / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D019301:Oleic Acid / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000633:toxicity; D011809:Quinones / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D047428:Protein Kinase Inhibitors; D011809:Quinones; C085278:hydroxysafflor yellow A; D019301:Oleic Acid; D002599:Chalcone; D017868:Cyclic AMP-Dependent Protein Kinases
Acute lung injury; Hydroxysafflor yellow A; Nicotinamide adenine dinucleotide phosphate oxidase; Protein kinase A; ROS; cAMP