Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib ameliorates influenza-virus-induced pneumonia in mice
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
Authors: Liu, Wei; Ren, Xiaojuan; Wang, Qian; Zhang, Yan; Du, Junfeng
Abstract
Treatments against influenza A viruses (IAV) have to be updated regularly due to antigenic drift and drug resistance. Poly (ADP-ribose) polymerases (PARPs) are considered effective therapeutic targets of acute lung inflammatory injury. This study aimed to explore the effects of PARP-1 inhibitor olaparib on IAV-induced lung injury and the underlying mechanisms. Male wild-type C57BL/6 mice were intranasally infected with IAV strain H1N1 to mimic pneumonia experimentally. Olaparib at different doses was intraperitoneally injected 2 days before and 5 consecutive days after virus stimulation. On day 6 post-infection, lung tissues as well as bronchoalveolar lavage fluid (BALF) were sampled for histological and biochemical analyses. Olaparib increased the survival rate of IAV mice dose-dependently. Olaparib remarkably reduced IAV mRNA expression, myeloperoxidase (MPO) level, and inflammatory cell infiltration in IAV lungs. Moreover, olaparib significantly reduced the level of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-6, and IL-4 and increased IL-10 in IAV lungs. Also, olaparib efficiently reduced IL-6, monocyte chemotactic protein (MCP)-1, granulocyte colony-stimulating factor (G-CSF), TNF-alpha, chemokine (C-X-C motif) ligand (CXCL)1, CXCL10, chemokine (C-C motif) ligand (CCL)3, and regulated on activation, normal T cell expressed and secreted (RANTES) release in IAV BALF. Olaparib decreased PARylated protein content and p65, I kappa B alpha phosphorylation in IAV lung tissues.This study successfully constructed the pneumonia murine model using IAV. Olaparib decreased IAV-induced mortality in mice, lung injury, and cytokine production possibly via modulation of PARP-1/NF-kappa B axis.
A new prenylated 3-benzoxepin derivative with anti-influenza A virus activity fromElsholtzia penduliflora
NATURAL PRODUCT RESEARCH
Authors: Zhang, Lu; Yang, Linyao; Li, Rong-Tao; Yu, Fei; Zhong, Jindong
Abstract
A new prenylated 3-benzoxepin derivative, elsholtzioxin (1), together with fifteen known compounds (2-16) were isolated from the whole parts ofElsholtzia penduliflora.Their structures were elucidated on the basis of various spectroscopic techniques and chemical evidences. The antiviral activities of these compounds were evaluatedin vitro. The new compound (1) exhibited potential anti-influenza virus activity against strain A/WSN/33/2009 (H1N1) with inhibition rate of 47.19%. Compounds2,9and12exhibited significant inhibitory activities with IC(50)value of 26.16, 34.66 and 20.81 mu M, respectively.