Abstract
BackgroundInfections 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.MethodThe 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.ResultINAE 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 α (IFN-α), interferon β (IFN-β), 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-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05).ConclusionThe 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.
Highlights
IntroductionThe current outbreak of novel coronavirus disease 19 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a big threat to the world [1]
The results showed that Aqueous extract of Indigo Naturalis (INAE) alleviated influenza A virus (IAV) induced acute lung injury (ALI) in mice
According to the well-known phytochemical compounds from Indigo Naturalis, chemical name, MS1 data, fragment of MS2 data, retention times and m/z values of the molecular ions, 19 chemicals were identified from INAE as Table 1 and Fig. 1: 13 alkaloids, 3 nucleosides, 1 terpene, 1 amino acid and 1 original acid
Summary
The current outbreak of novel coronavirus disease 19 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a big threat to the world [1]. Influenza A virus (IAV) is one of the important human pathogens worldwide. IAV infection can cause acute respiratory distress syndrome (ARDS), pneumonia, and lead to high mortality and morbidity [3]. Just like the current coronavirus pandemic which has spread over 200 countries and regions, fast spread of IAV infection may cause epidemic and threat people’s safety and property [4]. 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
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