Oral administration of Ulmus davidiana extract suppresses interleukin-1β expression in LPS-induced immune responses and lung injury

Genes Genomics. 2020 Jan;42(1):87-95. doi: 10.1007/s13258-019-00883-x. Epub 2019 Nov 17.

Abstract

Background: Ulmus davidiana (UD) is a traditional Korean herb medicine that is used to treat inflammatory disorders. UD has been shown to modulate a number of inflammatory processes in vitro or in vivo studies. However, the molecular mechanisms of UD on lipopolysaccharide (LPS)-induced acute lung injury remain to be understood.

Objective: The primary objective of this study is to determine the effect of UD bark water extract on LPS-induced immune responses and lung injury using both in vitro and in vivo models.

Methods: RAW 264.7 cells and a rat model of acute lung injury (ALI) were used to study the effects of UD on several parameters. Nitrite level, lactate dehydrogenase (LDH) level, and superoxide dismutase (SOD) activities were measured. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and plasma transaminase activities in blood were also determined. Pathological investigations were also performed.

Results: LPS infusion resulted in elevated IL-1β mRNA expression, nitrite levels, TNF-α expression, and IL-1β expression in RAW 264.7 cells. LPS infusion also increased levels of nitrite/nitrate, total protein, LDH, and TNF-α in bronchoalveolar lavage fluid, but reduced SOD levels in ex vivo and in vivo models. UD administration ameliorated all these inflammatory markers. In particular, treatment with UD reduced LPS-induced nitrite production in RAW 264.7 cells in a dose-dependent manner. UD treatment also counteracted the LPS-induced increase in alanine aminotransferase (ALT) and aspartate transaminase (AST) activity in rat plasma, leading to a significant reduction in ALT and AST activity.

Conclusions: The results revealed that UD treatment reduces LPS-induced nitrite production, IL-1β mRNA expression, and TNF-α expression. In addition, LPS-induced decrease in SOD level is significantly elevated by UD administration. These results indicate that UD extract merits consideration as a potential drug for treating and/or preventing ALI.

Keywords: Acute lung injury; Animal model; Lipopolysaccharide; Ulmus davidiana.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / immunology
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / prevention & control*
  • Administration, Oral
  • Animals
  • Gene Expression Regulation / drug effects*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Plant Extracts / administration & dosage*
  • Plant Extracts / pharmacology
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / chemically induced
  • Respiratory Distress Syndrome / immunology
  • Respiratory Distress Syndrome / metabolism
  • Respiratory Distress Syndrome / prevention & control*
  • Ulmus / chemistry*

Substances

  • Interleukin-1beta
  • Lipopolysaccharides
  • Plant Extracts