Kangaoheji Relieves Acute Lung Injury through p38 MAPK/NF-κB Signaling Pathway and ACE2/Ang1-7/Mas Axis

  OBJECTIVE  To explore the effect and mechanism of Kangaoheji (KAHJ) in the treatment of acute lung injury (ALI) in mice, and provide a rationale for its possible use as a drug to alleviate symptoms following coronavirus disease 2019 (COVID-19) infection.

  METHODS  Network pharmacology was carried out to predict the main active components and potential targets of KAHJ on ALI. C57BL/6J mice were randomly divided into Control group, LPS group and LPS+KAHJ group. LPS+KAHJ group was gavaged with KAHJ (4.76 g·kg^-1·d^-1, 8.8 mL·kg^-1·d^-1) and the rest of the groups were gavaged with saline (8.8 mL·kg^-1·d^-1). LPS (5 mg·kg^-1) was injected intraperitoneally to induce an acute inflammation model after 14 d. The serum and lung tissues of mice were collected, and the pathological changes in lung tissues were observed via histopathology. Western blot, Real-time PCR, Enzyme-Linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were used to assess the ameliorative effect of KAHJ on ALI.

  RESULTS  The result showed that 70 core target genes of KAHJ on ALI were primarily implicated in multiple signaling pathways involving MAPK signaling pathway, NF-κB signaling pathway, apoptosis, and Ras signaling pathway. Furthermore, we found that KAHJ ameliorated inflammation and apoptosis in ALI, thereby reducing lung damage and pulmonary edema and inhibiting pulmonary fibrosis. Additionally, KAHJ inhibited the phosphorylation of p38 MAPK and NF-κB, and upregulated the ACE2/Ang1-7/Mas axis.

  CONCLUSION  KAHJ might relieve acute lung injury through p38 MAPK/NF-κB signaling pathway and ACE2/Ang1-7/Mas axis, which offers complementary and alternative treatment options for COVID-19.