The Effect of the Prethanol Extract of Trifolium pratense Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes

Cells Tissues Organs. 2018;206(1-2):95-105. doi: 10.1159/000496108. Epub 2019 Jan 31.

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by cartilage degradation and inflammation. The proinflammatory cytokine, interleukin (IL)-1β, plays a crucial role in the pathogenesis of OA by inducing the release of other catabolic factors that contribute to cartilage degradation. Trifolium pratense L. (red clover) has been used as a medicinal plant in many countries and as a source of nutraceuticals to alleviate the symptoms of menopause. Ob-jectives: In this study, we aimed to evaluate the anticatabolic effect of 40% prethanol extract of T. pratense (40% PeTP) on IL-1β-stimulated chondrocytes.

Methods: Primary rat chondrocytes were pretreated with 40% PeTP for 1 h before stimulation with IL-1β (20 ng/mL). The production of nitrite, prostaglandin E2 (PGE2), and aggrecan was measured by using Griess reagent and ELISA. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4, mitogen-activated protein kinase (MAPK), and the nuclear factor (NF)-κB p65 subunit was measured by using Western blotting.

Results: PeTP (40%) significantly inhibited the IL-1β-induced expression of nitrite, iNOS, PGE2, COX-2, MMP-1, MMP-3, MMP-13, and ADAMTS-4 in isolated primary rat chondrocytes. Furthermore, 40% PeTP decreased the IL-1β-induced degradation of aggrecan, the phosphorylation of MAPKs, and the nuclear translocation of the NF-κB p65 subunit.

Conclusion: These results suggested that 40% PeTP has a chondroprotective effect on inflammation and may be a potential preventative agent for OA progression.

Keywords: Chondroprotective effect; Interleukin-1β; Osteoarthritis; Trifolium pratense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / immunology
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / immunology
  • Dinoprostone / immunology
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Interleukin-1beta / immunology*
  • Nitric Oxide / immunology
  • Osteoarthritis / drug therapy
  • Osteoarthritis / immunology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Trifolium / chemistry*

Substances

  • Aggrecans
  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Plant Extracts
  • Nitric Oxide
  • Dinoprostone