ReferenceID 5077
Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation
Acta Pharmacol Sin
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce acute inflammatory response like acute lung inflammation (ALI) or acute respiratory distress syndrome, leading to severe progression and mortality.
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- Reference Id
- 5077
- Evidence Id
- 21667
- Core Evidence Id
- 21667
- Source Reference Id
- 3435
- Herb2 Reference Id
- HBREF004232
- Subject Paper Key
- HBIN022650_34267343
- Pubmed Id
- 34267343
- Doi
- 10.1038/s41401-021-00714-4
- Paper Title
- Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation
- Paper Abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce acute inflammatory response like acute lung inflammation (ALI) or acute respiratory distress syndrome, leading to severe progression and mortality. Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered. Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection. In this study, we investigated the antiviral effects of a Salvia miltiorrhiza compound, Danshensu, in vitro and in vivo, including the mechanism of S protein-mediated virus attachment and entry into target cells. In authentic and pseudo-typed virus assays in vitro, Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 muM, and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus (SARS-CoV-2 S) into ACE2-overexpressed HEK-293T cells (IC50 = 0.31 muM) and Vero-E6 cell (IC50 = 4.97 muM). Mice received SARS-CoV-2 S via trachea to induce ALI, while the VSV-G treated mice served as controls. The mice were administered Danshensu (25, 50, 100 mg/kg, i.v., once) or Danshensu (25, 50, 100 mg kg-1 d-1, oral administration, for 7 days) before SARS-CoV-2 S infection. We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration, severely damaged lung tissue structure, highly expressed levels of inflammatory cytokines, and activated TLR4 and hyperphosphorylation of the NF-kappaB p65; the high expression of angiotensinogen (AGT) and low expression of ACE2 at the mRNA level in the lung tissue were also observed. Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S. This study not only establishes a mouse model of pseudo-typed SARS-CoV-2 (SARS-CoV-2 S) induced ALI, but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.
- Journal
- Acta Pharmacol Sin
- Publish Year
- 2021
- Experiment Subject
- mouse; patient; hek-293t cells; vero-e6 cell
- Experiment Type
- Animal Experiment
- Phenotype Related
- Severe Acute Respiratory Syndrome Coronavirus 2; Respiratory Inflammation; Inflammatory Cell Infiltration; Acute Respiratory Distress Syndrome; Sars-cov-2; Acute Lung Inflammation
- Paper Title Cn
- Paper Title En
- Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation
- Bilingual Status
- semi_complete