PMID- 30668313 OWN - NLM STAT- MEDLINE DCOM- 20190715 LR - 20190715 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 57 DP - 2019 Apr TI - In vivo effect of quantified flavonoids-enriched extract of Scutellaria baicalensis root on acute lung injury induced by influenza A virus. PG - 105-116 LID - S0944-7113(18)30603-2 [pii] LID - 10.1016/j.phymed.2018.12.009 [doi] AB - 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-alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), and increasing the levels of interferon-gamma (IFN-gamma) 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. CI - Copyright (c) 2018 Elsevier GmbH. All rights reserved. FAU - Zhi, Hai-Juan AU - Zhi HJ AD - Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China. FAU - Zhu, Hai-Yan AU - Zhu HY AD - Department of Microbiological and Biochemical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China. FAU - Zhang, Yun-Yi AU - Zhang YY AD - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. FAU - Lu, Yan AU - Lu Y AD - Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China. FAU - Li, Hong AU - Li H AD - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: lxzhang@shmu.edu.cn. FAU - Chen, Dao-Feng AU - Chen DF AD - Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: dfchen@shmu.edu.cn. LA - eng PT - Journal Article DEP - 20181210 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antiviral Agents) RN - 0 (Flavonoids) RN - 0 (Plant Extracts) SB - IM MH - Acute Lung Injury/*drug therapy/virology MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology MH - Antiviral Agents/chemistry/*pharmacology MH - Dogs MH - Flavonoids/analysis/*pharmacology MH - Humans MH - Influenza A Virus, H1N1 Subtype/pathogenicity MH - Lung/drug effects/pathology/virology MH - Madin Darby Canine Kidney Cells MH - Mice, Inbred BALB C MH - Orthomyxoviridae Infections/*complications/drug therapy MH - Plant Extracts/pharmacology MH - Plant Roots/chemistry MH - Scutellaria baicalensis/*chemistry OTO - NOTNLM OT - Acute lung injury OT - Anti-complementary activity OT - Anti-inflammatory activity OT - Antiviral activity OT - Flavonoids-enriched extract from Scutellaria baicalensis root OT - Influenza A virus EDAT- 2019/01/23 06:00 MHDA- 2019/07/16 06:00 CRDT- 2019/01/23 06:00 PHST- 2018/09/03 00:00 [received] PHST- 2018/12/06 00:00 [revised] PHST- 2018/12/09 00:00 [accepted] PHST- 2019/01/23 06:00 [pubmed] PHST- 2019/07/16 06:00 [medline] PHST- 2019/01/23 06:00 [entrez] AID - S0944-7113(18)30603-2 [pii] AID - 10.1016/j.phymed.2018.12.009 [doi] PST - ppublish SO - Phytomedicine. 2019 Apr;57:105-116. doi: 10.1016/j.phymed.2018.12.009. Epub 2018 Dec 10.