In vivo effect of quantified flavonoids-enriched extract of Scutellaria baicalensis root on acute lung injury induced by influenza A virus

Phytomedicine. 2019 Apr;57:105-116. doi: 10.1016/j.phymed.2018.12.009. Epub 2018 Dec 10.

Abstract

Background: Scutellaria baicalensis root is traditionally used for the treatment of common cold, fever and influenza. Flavonoids are the major chemical components of S. baicalensis root.

Purpose: To evaluate the therapeutic effects and action mechanism of flavonoids-enriched extract from S. baicalensis root (FESR) on acute lung injury (ALI) induced by influenza A virus (IAV) in mice.

Methods: The anti-influenza, anti-inflammatory and anti-complementary properties of FESR and the main flavonoids were evaluated in vitro. Mice were challenged intranasally with influenza virus H1N1 (A/FM/1/47) 2 h before treatment. FESR (50, 100 and 200 mg/kg) was administrated intragastrically. Baicalin (BG), the most abundant compound in FESR was given as reference control. Survival rates, life spans and lung indexes of IAV-infected mice were measured. Histopathological changes, virus levels, inflammatory markers and complement deposition in lungs were analyzed.

Result: Compared with the main compound BG, FESR and lower content aglycones (baicalein, oroxylin A, wogonin and chrysin) in FESR significantly inhibited H1N1 activity in virus-infected Madin-Darby canine kidney (MDCK) cells and markedly decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In vitro assays showed that FESR and BG had no anti-complementary activity whereas baicalein, oroxylin A, wogonin and chrysin exhibited obvious anti-complementary activity. Oral administration of FESR effectively protected the IAV-infected mice, increased the survival rate (FESR: 67%; BG: 33%), decreased the lung index (FESR: 0.90; BG: 1.00) and improved the lung morphology in comparing with BG group. FESR efficiently decreased lung virus titers, reduced haemagglutinin (HA) titers and inhibited neuraminidase (NA) activities in lungs of IAV-infected mice. FESR modulated the inflammatory responses by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), and increasing the levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) in lung tissues. Although showing no anti-complementary activity in vitro, FESR obviously reduced complement deposition and decreased complement activation product level in the lung .

Conclusion: FESR has a great potential for the treatment of ALI induced by IAV and the underlying action mechanism might be closely associated with antiviral, anti-inflammatory and anti-complementary properties. Furthermore, FESR resulted in more potent therapeutic effect than BG in the treatment of IAV-induced ALI.

Keywords: Acute lung injury; Anti-complementary activity; Anti-inflammatory activity; Antiviral activity; Flavonoids-enriched extract from Scutellaria baicalensis root; Influenza A virus.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / virology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dogs
  • Flavonoids / analysis
  • Flavonoids / pharmacology*
  • Humans
  • Influenza A Virus, H1N1 Subtype / pathogenicity
  • Lung / drug effects
  • Lung / pathology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / complications*
  • Orthomyxoviridae Infections / drug therapy
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • Scutellaria baicalensis / chemistry*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antiviral Agents
  • Flavonoids
  • Plant Extracts