Chondroprotective effects of aqueous extract of Anthriscus sylvestris leaves on osteoarthritis in vitro and in vivo through MAPKs and NF-κB signaling inhibition

Biomed Pharmacother. 2018 Jul:103:1202-1211. doi: 10.1016/j.biopha.2018.04.183. Epub 2018 May 7.

Abstract

Osteoarthritis (OA) is a common degenerative joint disease, characterized by cartilage degradation and inflammation, in the elderly population. Anthriscus sylvestris has been used in Korean traditional medicine and contains many polyphenolic compounds such as cynaroside and chlorogenic acid, which are major active components responsible for its antioxidant effect. In this study, we aimed to evaluate the chondroprotective effect of an aqueous extract of A. sylvestris leaves (AE-ASL) on OA, both in vitro and in vivo. Rat primary chondrocytes were pretreated with AE-ASL for 1 h before interleukin-1β (20 ng/mL) stimulation. The production of nitrite, PGE2, aggrecan, and collagen type II were detected by Griess reagent and ELISAs. The mRNA levels of iNOS, COX-2, MMP-3, and MMP-13 were measured by RT-PCR. In addition, protein levels of iNOS, COX-2, MMP-3, MMP-13, ADAMTS-4, MAPKs, and NF-κB p65 subunit were measured by western blot analysis. Sulfated glycosaminoglycan (sGAGs) were detected by dimethylmethylene blue (DMMB) assay. During in vivo study, the effects of AE-ASL were evaluated for 8 weeks in a rat model of destabilization of the medial meniscus (DMM) surgery-induced OA. AE-ASL significantly inhibited expression of nitrite, iNOS, PGE2, COX-2, MMP-3, MMP-13, and ADAMTS-4 in IL-1β-stimulated chondrocytes. Moreover, it decreased the IL-1β-induced degradation of aggrecan, collagen type II, and proteoglycan. In addition, AE-ASL suppressed IL-1β-induced phosphorylation of MAPKs and NF-κB p65 subunit translocation to nucleus. In vivo, AE-ASL inhibited DMM surgery-induced cartilage destruction and proteoglycan loss. Taken together, these results suggest that AE-ASL may be a potential therapeutic agent for the alleviation of OA progression.

Keywords: Anthriscus sylvestris; Articular cartilage; Chondroprotective effect; Inflammation; Osteoarthritis.

MeSH terms

  • Animals
  • Apiaceae / chemistry*
  • Cartilage, Articular / pathology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology*
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / pharmacology
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Nitrites / metabolism
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / enzymology
  • Osteoarthritis / pathology
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Water

Substances

  • Inflammation Mediators
  • Interleukin-1beta
  • NF-kappa B
  • Nitrites
  • Plant Extracts
  • Protective Agents
  • Water
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3
  • Dinoprostone