Hesperidin attenuates influenza A virus (H1N1)-induced lung injury in rats through its anti-inflammatory effect

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.

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Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice

Critical Care Medicine ◽

10.1097/ccm.0b013e3182676352 ◽

2013 ◽

Vol 41 (1) ◽

pp. 171-181 ◽

Cited By ~ 23

Author(s):

Masato Yashiro ◽

Hirokazu Tsukahara ◽

Akihiro Matsukawa ◽

Mutsuko Yamada ◽

Yosuke Fujii ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Influenza A ◽

Virus H1n1 ◽

Active Protein ◽

Redox Active ◽

Thioredoxin 1

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Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

Chinese Medicine ◽

10.1186/s13020-020-00415-w ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Peng Tu ◽

Rong Tian ◽

Yan Lu ◽

Yunyi Zhang ◽

Haiyan Zhu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Lung Tissue ◽

Influenza A ◽

Influenza Viruses ◽

No Production ◽

Indigo Naturalis ◽

Anti Inflammatory

Abstract 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 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). 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.

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Beneficial effect of indigo naturalis on acute lung injury induced by influenza A virus

10.21203/rs.3.rs-73166/v2 ◽

2020 ◽

Author(s):

Peng Tu ◽

Rong Tian ◽

Yan Lu ◽

Yunyi Zhang ◽

Haiyan Zhu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Lung Tissue ◽

Influenza A ◽

Influenza Viruses ◽

No Production ◽

Indigo Naturalis ◽

Anti Inflammatory

Abstract 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-1/d) 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 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).Conclusion: The results showed that INae alleviated IAV induced ALI in mice. The effect of INAE might be related with its anti-influenza, 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.

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Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

10.21203/rs.3.rs-73166/v3 ◽

2020 ◽

Author(s):

Peng Tu ◽

Rong Tian ◽

Yan Lu ◽

Yunyi Zhang ◽

Haiyan Zhu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Lung Tissue ◽

Influenza A ◽

Influenza Viruses ◽

No Production ◽

Indigo Naturalis ◽

Anti Inflammatory

Abstract 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-1/d) 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 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).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.

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CircRNA expression profiling and bioinformatics analysis indicate the potential biological role and clinical significance of circRNA in influenza A virus-induced lung injury

Journal of Biosciences ◽

10.1007/s12038-021-00152-8 ◽

2021 ◽

Vol 46 (2) ◽

Author(s):

Jiajia Wang ◽

Yanbing Zhang ◽

Fengfeng Zhu ◽

Liling Chen ◽

Yao Wei ◽

...

Keyword(s):

Lung Injury ◽

Clinical Significance ◽

Influenza A Virus ◽

Expression Profiling ◽

Influenza A ◽

Bioinformatics Analysis ◽

Biological Role

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Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice

Dose-Response ◽

10.1177/15593258211011335 ◽

2021 ◽

Vol 19 (2) ◽

pp. 155932582110113

Author(s):

Rufeng Lu ◽

Yueguo Wu ◽

Honggang Guo ◽

Zhuoyi Zhang ◽

Yuzhou He

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Influenza A ◽

H1n1 Virus ◽

Antiviral Agents ◽

Toll Like Receptor ◽

Virus Infections ◽

Toll Like Receptor 4 ◽

Inflammatory Cytokine Production

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

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PP-069 Neuraminidase N1 of the 2009 pandemic swine-origin influenza A virus H1N1 has a Group-2 specific active cavity

International Journal of Infectious Diseases ◽

10.1016/s1201-9712(10)60137-3 ◽

2010 ◽

Vol 14 ◽

pp. S46

Author(s):

Q. Li ◽

J.X. Qi ◽

G.F. Gao

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Virus H1n1 ◽

Group 2

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Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.5.g974 ◽

2001 ◽

Vol 280 (5) ◽

pp. G974-G978 ◽

Cited By ~ 36

Author(s):

Madhav Bhatia ◽

Ashok K. Saluja ◽

Vijay P. Singh ◽

Jean-Louis Frossard ◽

Hong-Sik Lee ◽

...

Keyword(s):

Acute Pancreatitis ◽

Lung Injury ◽

Acute Inflammation ◽

Complement Factor ◽

Neutrophil Sequestration ◽

C5a Receptors ◽

Acinar Cell Necrosis ◽

Anti Inflammatory ◽

Type Strains ◽

Inflammatory Effect

Complement factor C5a acting via C5a receptors (C5aR) is recognized as an anaphylotoxin and chemoattractant that exerts proinflammatory effects in many pathological states. The effects of C5a and C5aR in acute pancreatitis and in pancreatitis-associated lung injury were evaluated using genetically altered mice that either lack C5aR or do not express C5. Pancreatitis was induced by administration of 12 hourly injections of cerulein (50 μg/kg ip). The severity of pancreatitis was determined by measuring serum amylase, neutrophil sequestration in the pancreas, and acinar cell necrosis. The severity of lung injury was evaluated by measuring neutrophil sequestration in the lung and pulmonary microvascular permeability. In both strains of genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was greater than that noted in the comparison wild-type strains of C5aR- and C5-sufficient animals. This exacerbation of injury in the absence of C5a function indicates that, in pancreatitis, C5a exerts an anti-inflammatory effect. Potentially, C5a and its receptor are capable of both promoting and reducing the extent of acute inflammation.

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