Acetylated derivative of glaucine inhibits joint inflammation in collagenase-induced arthritis

Immunopharmacol Immunotoxicol. 2015 Feb;37(1):56-62. doi: 10.3109/08923973.2014.972414. Epub 2014 Oct 20.

Abstract

Context: Osteoarthritis (OA) has become by far the most common joint disorder. A number of studies using OA animal models have explored the effects of agents that can modulate bone metabolism.

Objective: In the present study, we investigated the effect of acetylated derivative of plant alkaloid glaucine (ADG) on experimental OA in mice.

Materials and methods: Arthritis was induced by two intraarticular (i.a.) injections of collaganase. Histopathological changes were observed through hematoxylin and eosine (H&E), safranin O and toluidine blue staining. Differentiation of bone marrow (BM) cells was evaluated by tartarate-resistant acid phosphatase (TRAP) assay. The expression of phospho-Janus kinase 2 (pJAK2) and phospho signal transducer and activator of transcription3 (pSTAT3) expression in the joints was determined by immunohistochemistry.

Results: We established that ADG significantly decreased cell infiltration (2.32 ± 0.14 versus 1.62 ± 0.13), cartilage loss (2.42 ± 0.12 versus 1.12 ± 0.10) and bone erosion (1.76 ± 0.13 versus 1.04 ± 0.14) in arthritic mice. It appeared that the substance inhibited in a dose-dependent manner osteoclast differentiation in vitro. ADG suppressed the expression of pJAK2 in the joint and partially affected the expression of pSTAT3.

Conclusion: Present results suggest that ADG is a suitable candidate for further development as an anti-arthritic agent.

Keywords: Acetylated derivative of glaucine; JAK–STAT pathway; collagenase-induced osteoarthritis; osteoclastogenesis; proteoglycans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aporphines / administration & dosage
  • Aporphines / adverse effects
  • Aporphines / chemistry
  • Aporphines / therapeutic use*
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Bone Marrow Cells / drug effects
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Joints / drug effects*
  • Joints / enzymology
  • Joints / pathology
  • Male
  • Mice, Inbred ICR
  • Microbial Collagenase / pharmacology*
  • Molecular Structure
  • Osteoarthritis / chemically induced
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / pathology
  • Osteoclasts / drug effects
  • Osteoclasts / immunology
  • Osteoclasts / pathology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Aporphines
  • Microbial Collagenase
  • glaucine