title: Mosla scabra flavonoids ameliorate the influenza A virus-induced lung injury and water transport abnormality via the inhibition of PRR and AQP signaling pathways in mice.
abstract: BACKGROUND
  Mosla scabra (Thunb.) C.Y. Wu and H.W. Li has been used as a traditional medicinal herb for centuries in East Asian countries. It has antibacterial, antiviral, antioxidant, anti-inflammatory and immunomodulatory effects. In folk medicine, it is used as a remedy for the treatment of pulmonary diseases, such as fever, cold, cough, pulmonary edema and emphysema.
  
  
  OBJECTIVE
  This study was to investigate the protective mechanism of total flavonoids from M. scabra (MF) in influenza A virus (IAV)-infected mice.
  
  
  METHODS
  The mice were infected with IAV and then were treated daily with MF for five days. At the end of the experiment, the levels of inflammatory-related cytokines (IFN-α, IL-6, TNF-α and IL-1β) were determined by ELISA. Pathological changes of lung tissue were examined by H&E staining. The protein expressions of AQP5, p-p38, caspase-3 and NF-κB p65 were detected by western blot analysis while the gene expressions of key effectors in AQP5 and PRRs signaling pathways were detected by real-time Fluorescence Quantitative Polymerase Chain Reaction (RFQ-PCR) analysis.
  
  
  RESULTS
  The results showed that treatment with MF at doses of 120-360mg/kg for five days to IAV-infected mice significantly attenuated IAV-induced pulmonary injury and decreased the serum levels of IL-6, TNF-α and IL-1β, but increased IFN-α levels. MF treatment could up-regulate the mRNA expressions of TLR-7, RIG-1, TRAF6, Bcl-2, Bax, VIPR1, PKCα and AQP5 and down-regulate caspase-3 and NF-κB p65 protein expression.
  
  
  CONCLUSIONS
  Treatment with MF could significantly alleviate IAV-induced pulmonary inflammation, apoptosis and water transport abnormality, which was probably through the regulation of TLR7, RIG-1 and AQP5 signaling pathway.
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Yu
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China; College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Pharmaceutical Department, Zhejiang Medical College, Hangzhou 310053, China. Electronic address: Jellycook2002@163.com.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Wu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020346:Aquaporins / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019686:Lamiaceae / Q000737:chemistry*; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051192:Receptors, Pattern Recognition / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D020346:Aquaporins; D016207:Cytokines; D005419:Flavonoids; D051192:Receptors, Pattern Recognition; D014660:Vasoactive Intestinal Peptide
keywords: Antiviral; Apoptosis; Aquaporin 5; Inflammation; Vasoactive intestinal peptide