Salvianolic acid B ameliorates liver injury in a murine aGvHD model by decreasing inflammatory responses via upregulation of HO-1

Transpl Immunol. 2019 Aug:55:101203. doi: 10.1016/j.trim.2019.03.002. Epub 2019 Mar 20.

Abstract

Acute graft-versus-host disease (aGvHD) remains lethal, even after allogeneic hematopoietic stem cell transplantation. Inflammatory responses play an important role in aGvHD. Salvianolic acid B (Sal B) has been widely reported to have a major effect on the anti-inflammatory response, but these effects in an aGvHD model have never been reported. B6 donor splenocytes were transplanted into unirradiated BDF1 recipients and liver and serum were collected on day 14 after transplantation with or without Sal B administration. We measured the expression of pro-inflammatory cytokines and chemokines and other manifestations in aGvHD mice after Sal B treatment. Sal B ameliorated liver injury in aGvHD and promoted survival in mice. Sal B treatment resulted in decreased expression of pro-inflammatory cytokines and chemokines whose expressions in liver are normally elevated by aGvHD. Furthermore, Sal B treatment also enhanced PGC-1α expression in liver tissue and HO-1 expression in nonparenchymal cells. In addition, HO-1 inhibitor abrogated the improvement of survival rate of mice with aGvHD. These results indicated that the protective effect of Sal B relies on suppressing the inflammatory response phase in the aGvHD model, presumably by inducing HO-1. Taken together our data showed that Sal B ameliorates liver injury in aGvHD by decreasing inflammatory responses via upregulation of HO-1. It may provide a novel way to deal with this disease.

Keywords: Acute graft-versus-host disease; HO-1; Inflammatory cytokines; PGC-1α; Salvianolic acid B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Benzofurans / pharmacology*
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Enzymologic / immunology
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Heme Oxygenase-1 / immunology*
  • Inflammation / immunology
  • Inflammation / pathology
  • Liver / immunology*
  • Liver / injuries
  • Liver / pathology
  • Liver Diseases / immunology*
  • Liver Diseases / pathology
  • Male
  • Membrane Proteins / immunology*
  • Mice
  • Up-Regulation / drug effects*
  • Up-Regulation / immunology

Substances

  • Benzofurans
  • Membrane Proteins
  • salvianolic acid B
  • Heme Oxygenase-1
  • Hmox1 protein, mouse