Suppressive effect of Sanmiao formula on experimental gouty arthritis by inhibiting cartilage matrix degradation: An in vivo and in vitro study

Int Immunopharmacol. 2016 Jan:30:36-42. doi: 10.1016/j.intimp.2015.11.010. Epub 2015 Nov 27.

Abstract

Sanmiao formula (SM) is a compound prescription, which has been used in traditional Chinese medicine since the Ming Dynasty for gouty and rheumatoid arthritis treatments. However, no evidence has been unfolded to show the relationship between SM and gouty arthritis (GA), particularly inhibiting cartilage matrix degradation. In the present study, we undertook a characterization of anti-GA activity of SM using an in vivo rat model induced by potassium oxonate and cold bath together with in vitro studies with chondrocytes for further molecular characterization. Potassium oxonate and cold bath rats were treated with SM at doses of 7.2g/kg per day for 5days. SM treatments significantly suppressed the swelling rate and the severe pathologic changes in the joints of the animals in gout model. Inflammatory factors count by ELISA analysis, SM exhibited inhibition on IL-1β and TNF-α. Moreover, histological analysis of the joints and SM-serum substantially interfered with the MSU-induced expression of glycosaminoglycans (GAG), up-regulated the content of proteoglycan. Importantly, SM interfered with GA-augmented expression of matrix metalloproteinases (MMPs) -3 and aggrecanases (ADAMTS)-4, which are considered to be key enzymes in cartilage matrix degradation, and simultaneously augmented GA-reduced tissue inhibitors of metalloproteinases (TIMPs) -1 and -3 expression in the joints and chondrocytes. Therefore, SM is looking forward to be a potential novel agent that could prevent cartilage matrix degradation effectively in gouty arthritis, and this provides a new target for development of new medicines.

Keywords: Cartilage matrix; Chondrocytes; Gouty arthritis; Proteoglycan; Sanmiao formula.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAMTS4 Protein
  • Animals
  • Arthritis, Gouty / chemically induced
  • Arthritis, Gouty / drug therapy*
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / physiology
  • Complex Mixtures / administration & dosage*
  • Down-Regulation
  • Drugs, Chinese Herbal / administration & dosage*
  • Humans
  • Hydrolysis / drug effects
  • Hydrolysis / radiation effects
  • Interleukin-1beta / metabolism
  • Joints / drug effects*
  • Joints / pathology
  • Male
  • Matrilin Proteins / metabolism*
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Medicine, Chinese Traditional*
  • Models, Animal
  • Oxonic Acid / administration & dosage
  • Procollagen N-Endopeptidase / genetics
  • Procollagen N-Endopeptidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Complex Mixtures
  • Drugs, Chinese Herbal
  • Interleukin-1beta
  • Matrilin Proteins
  • Tumor Necrosis Factor-alpha
  • potassium oxonate
  • Oxonic Acid
  • ADAM Proteins
  • Procollagen N-Endopeptidase
  • Matrix Metalloproteinase 3
  • ADAMTS4 Protein
  • ADAMTS4 protein, human