Dehydroevodiamine suppresses inflammatory responses in adjuvant-induced arthritis rats and human fibroblast-like synoviocytes

Bioengineered. 2022 Jan;13(1):268-279. doi: 10.1080/21655979.2021.1999554.

Abstract

Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus, which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund's Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1βand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.

Keywords: Dehydroevodiamine; aia; mapk; mh7a; rheumatoid arthritis.

Publication types

  • Retracted Publication

MeSH terms

  • Alkaloids / administration & dosage*
  • Alkaloids / pharmacology
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / immunology
  • Body Weight / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Freund's Adjuvant / adverse effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Rats
  • Synoviocytes / cytology*
  • Synoviocytes / drug effects
  • Synoviocytes / immunology

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Cytokines
  • dehydroevodiamine
  • Freund's Adjuvant
  • Matrix Metalloproteinases

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.