Natural Compound Oridonin Inhibits Endotoxin-Induced Inflammatory Response of Activated Hepatic Stellate Cells

Claire B. Cummins, Xiaofu Wang, Christian Sommerhalder, Frederick J. Bohanon, Omar Nunez Lopez, Hong Yan Tie, Victoria G. Rontoyanni, Jia Zhou, Ravi Radhakrishnan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis and inflammatory modulation. Endotoxin is dramatically increased in portal venous blood after serious injury and can contribute to liver damage. However, the mechanism underlying endotoxin's effects on HSCs remains largely unknown. Oridonin is a bioactive diterpenoid isolated from Rabdosia rubescens that exhibits anti-inflammatory properties in different tissues. In the present study, we determined the effects of oridonin on endotoxin-induced inflammatory response and signaling pathways in vitro. The production of proinflammatory cytokines in activated human HSCs line LX-2 was measured by ELISA and Western blots. Immunofluorescence and nuclear fractionation assay were used to determine NF-B activity. Oridonin treatment significantly inhibited LPS-induced proinflammatory cytokines IL-1β, IL-6, and MCP-1 production as well as cell adhesion molecules ICAM-1 and VCAM-1. Additionally, oridonin blocked LPS-induced NF-B p65 nuclear translocation and DNA binding activity. Oridonin prevented LPS-stimulated NF-B regulator IKKα/β and IBα phosphorylation and IBα degradation. Combined treatment of oridonin and an Hsp70 substrate binding inhibitor synergistically suppressed LPS-stimulated proinflammatory cytokines and NF-B pathway activation. Therefore, oridonin inhibits LPS-stimulated proinflammatory mediators through IKK/IBα/NF-B pathway. Oridonin could be a promising agent for a hepatic anti-inflammatory.

Original languageEnglish (US)
Article number6137420
JournalBioMed Research International
Volume2018
DOIs
StatePublished - Jan 1 2018

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Hepatic Stellate Cells
Endotoxins
Cytokines
Liver
Isodon
Anti-Inflammatory Agents
Phosphorylation
Vascular Cell Adhesion Molecule-1
oridonin
Diterpenes
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Fractionation
Interleukin-1
Fluorescent Antibody Technique
Interleukin-6
Assays
Blood
Western Blotting
Chemical activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Natural Compound Oridonin Inhibits Endotoxin-Induced Inflammatory Response of Activated Hepatic Stellate Cells. / Cummins, Claire B.; Wang, Xiaofu; Sommerhalder, Christian; Bohanon, Frederick J.; Nunez Lopez, Omar; Tie, Hong Yan; Rontoyanni, Victoria G.; Zhou, Jia; Radhakrishnan, Ravi.

In: BioMed Research International, Vol. 2018, 6137420, 01.01.2018.

Research output: Contribution to journalArticle

Cummins, Claire B. ; Wang, Xiaofu ; Sommerhalder, Christian ; Bohanon, Frederick J. ; Nunez Lopez, Omar ; Tie, Hong Yan ; Rontoyanni, Victoria G. ; Zhou, Jia ; Radhakrishnan, Ravi. / Natural Compound Oridonin Inhibits Endotoxin-Induced Inflammatory Response of Activated Hepatic Stellate Cells. In: BioMed Research International. 2018 ; Vol. 2018.
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