Intragastric and atomized administration of canagliflozin inhibit inflammatory cytokine storm in lipopolysaccharide-treated sepsis in mice: A potential COVID-19 treatment

Yaoyun Niu; Yang Chen; Pengbo Sun; Yangyang Wang; Jingyi Luo; Yipei Ding; Weidong Xie

doi:10.1016/j.intimp.2021.107773

Intragastric and atomized administration of canagliflozin inhibit inflammatory cytokine storm in lipopolysaccharide-treated sepsis in mice: A potential COVID-19 treatment

Int Immunopharmacol. 2021 Jul:96:107773. doi: 10.1016/j.intimp.2021.107773. Epub 2021 May 9.

Authors

Yaoyun Niu¹, Yang Chen¹, Pengbo Sun², Yangyang Wang², Jingyi Luo¹, Yipei Ding¹, Weidong Xie³

Affiliations

¹ Key Lab in Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; State Key Laboratory of Chemical Oncogenomic, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
² Key Lab in Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; State Key Laboratory of Chemical Oncogenomic, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; Open FIESTA Center, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
³ Key Lab in Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; State Key Laboratory of Chemical Oncogenomic, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; Open FIESTA Center, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China. Electronic address: xiewd@sz.tsinghua.edu.cn.

Abstract

To date, drugs to attenuate cytokine storm in severe cases of Corona Virus Disease 2019 (COVID-19) are not available. In this study, we investigated the effects of intragastric and atomized administration of canagliflozin (CAN) on cytokine storm in lung tissues of lipopolysaccharides (LPS)-induced mice. Results showed that intragastric administration of CAN significantly and widely inhibited the production of inflammatory cytokines in lung tissues of LPS-induced sepsis mice. Simultaneously, intragastric administration of CAN significantly improved inflammatory pathological changes of lung tissues. Atomized administration of CAN also exhibited similar effects in LPS-induced sepsis mice. Furthermore, CAN significantly inhibited hypoxia inducible factor 1α (HIF-1α) and phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) protein levels in LPS-treated lung tissues. These results indicated that CAN might attenuate cytokine storm and reduce the inflammatory symptoms in critical cases in COVID-19. Its action mechanism might involve the regulation of HIF-1α and glycolysis in vivo. However, further studies about clinical application and mechanism analysis should be validated in the future.

Keywords: COVID-19; Canagliflozin; Cytokine storm; Inflammation.

MeSH terms

Animals
COVID-19 Drug Treatment*
Canagliflozin / pharmacology*
Cytokine Release Syndrome* / chemically induced
Lipopolysaccharides / toxicity
Male
Mice
SARS-CoV-2
Sepsis / chemically induced

Substances

Lipopolysaccharides
Canagliflozin