PMID- 33349263
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201225
IS  - 1749-8546 (Print)
IS  - 1749-8546 (Electronic)
IS  - 1749-8546 (Linking)
VI  - 15
IP  - 1
DP  - 2020 Dec 21
TI  - Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A 
      virus.
PG  - 128
LID - 10.1186/s13020-020-00415-w [doi]
LID - 128
AB  - BACKGROUND: Infections induced by influenza viruses, as well as coronavirus 
      disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 
      (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which 
      traditional Chinese medicine (TCM) played an important role in treatment of the 
      pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI 
      induced by influenza A virus (IAV) in mice. METHOD: The anti-influenza and 
      anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were 
      evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were 
      treated intragastrically with INAE (40, 80 and 160 mg/kg/day) 2 h later for 4 or 
      7 days. Animal lifespan and mortality were recorded. Expression of high mobility 
      group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated 
      through immunohistological staining. Inflammatory cytokines were also monitored 
      by ELISA. RESULT: INAE inhibited virus replication on Madin-Darby canine kidney 
      (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide 
      (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral 
      administration of 160 mg/kg of INAE significantly improved the lifespan 
      (P < 0.01) and survival rate of IAV infected mice, improved lung injury and 
      lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 
      and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), 
      as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). 
      Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were 
      reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in 
      lung tissue were also suppressed. The increased production of myeloperoxidase 
      (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE 
      treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon alpha 
      (IFN-alpha), interferon beta (IFN-beta), monocyte chemoattractant protein-1 (MCP-1), 
      regulated upon activation normal T cell expressed and secreted factor (RANTES), 
      interferon induced protein-10 (IP-10), tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-6 (IL-6) (P < 0.05), with increased production of interferon gamma 
      (IFN-gamma) and interleukin-10 (IL-10) (P < 0.05). CONCLUSION: The results showed 
      that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were 
      associated with its anti-influenza, anti-inflammatory and anti-oxidation 
      properties. Indigo Naturalis might have clinical potential to treat ALI induced 
      by IAV.
FAU - Tu, Peng
AU  - Tu P
AD  - Department of Natural Medicine, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Tian, Rong
AU  - Tian R
AD  - Department of Natural Medicine, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Lu, Yan
AU  - Lu Y
AD  - Department of Natural Medicine, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Zhang, Yunyi
AU  - Zhang Y
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Zhu, Haiyan
AU  - Zhu H
AD  - Department of Microbiological and Biochemical Pharmacy, School of Pharmacy, Fudan 
      University, No. 826, Zhangheng Road, Shanghai, 201203, People's Republic of 
      China.
FAU - Ling, Lijun
AU  - Ling L
AD  - Department of Natural Medicine, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China.
FAU - Li, Hong
AU  - Li H
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China. 
      lxzhang@shmu.edu.cn.
FAU - Chen, Daofeng
AU  - Chen D
AD  - Department of Natural Medicine, School of Pharmacy, Fudan University, No. 826, 
      Zhangheng Road, Shanghai, 201203, People's Republic of China. dfchen@shmu.edu.cn.
LA  - eng
GR  - 2019YFC 1711000/National Key R&D Program of China/
GR  - 81330089/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20201221
PL  - England
TA  - Chin Med
JT  - Chinese medicine
JID - 101265109
PMC - PMC7750395
OTO - NOTNLM
OT  - Acute lung injury
OT  - Cytokines
OT  - Indigo Naturalis
OT  - Inflammation
OT  - Influenza
COIS- The authors declare that there are no conflicts of interest regarding the 
      publication of this article.
EDAT- 2020/12/23 06:00
MHDA- 2020/12/23 06:01
PMCR- 2020/12/21
CRDT- 2020/12/22 05:33
PHST- 2020/09/05 00:00 [received]
PHST- 2020/12/11 00:00 [accepted]
PHST- 2020/12/22 05:33 [entrez]
PHST- 2020/12/23 06:00 [pubmed]
PHST- 2020/12/23 06:01 [medline]
PHST- 2020/12/21 00:00 [pmc-release]
AID - 10.1186/s13020-020-00415-w [pii]
AID - 415 [pii]
AID - 10.1186/s13020-020-00415-w [doi]
PST - epublish
SO  - Chin Med. 2020 Dec 21;15(1):128. doi: 10.1186/s13020-020-00415-w.