Abstract
Background: Infections induced by influenza viruses, as well as COVID-19 pandemic induced by SARS-CoV-2 led to Acute lung injury (ALI) and multiorgan failure, during which traditional Chinese medicine 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 extracts 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-1/d) 2 h later for 4 or 7 days. Animal mortality and lifespan 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 growth on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophage 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) also significantly increased liver weight and liver index (P < 0.05), as well as spleen and thymus weight and organ index at 160 mg/kg (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), interferon γ (IFN-γ), 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 interleukin-10 (IL-10) (P < 0.05). The increased myeloperoxidase (MPO) activity and methylene dioxyamphetamine (MDA) level in lung tissues were inhibited by INAE treatment (P < 0.05).Conclusion: The results showed that INae alleviated IAV induced ALI in mice. The effect of INAE might be related with its anti-virus, anti-inflammatory and anti-oxidation properties, which give a hint that indigo naturalis might be effective on respiratory viruses infected acute lung injury or SAR-CoV-2 caused COVID-19.
CircRNA expression profiling and bioinformatics analysis indicate the potential biological role and clinical significance of circRNA in influenza A virus-induced lung injury
