title: Effects of intra-articular SHINBARO treatment on monosodium iodoacetate-induced osteoarthritis in rats.
abstract: BACKGROUND
  SHINBARO is a refined herbal formulation used to treat inflamed lesions and bone diseases. This study aimed to investigate the anti-osteoarthritic activities of intra-articular administration of SHINBARO and determine its underlying molecular mechanism in a monosodium iodoacetate (MIA)-induced osteoarthritis rat model.
  
  
  METHODS
  Male Sprague-Dawley rats received a single intra-articular injection of MIA into the infrapatellar ligament of the right knee. Subsequently, the rats were treated with normal saline, SHINBARO, and diclofenac once daily for 21 days. Rats treated with normal saline, but not MIA, comprised the control group. Histological changes in the femur of the MIA-induced osteoarthritis rat model were observed by micro-computed tomography scanning and staining with hematoxylin and eosin, and safranin-O fast green. Serum levels of PGE2 and anti-type II collagen antibodies in the MIA-induced osteoarthritis rat model were measured using commercial kits. Protein levels of inflammatory enzymes (iNOS, COX-2), pro-inflammatory cytokines (TNF-α, IL-1β), and inflammatory mediators (NF-κB, IκB) in cartilaginous tissues were determined by western blot analysis.
  
  
  RESULTS
  Intra-articular administration of SHINBARO (IAS) at 20 mg/kg remarkably restrained the decrease in bone volume/total volume, being 28 % (P = 0.0001) higher than that in the vehicle-treated MIA group. IAS (2, 10, and 20 mg/kg) treatment significantly recovered the mean number of objects values with increased percentage changes of 13.5 % (P = 0.147), 27.5 % (P = 0.028), and 44.5 % (P = 0.031), respectively, compared with the vehicle-treated MIA group. The serum level of PGE2 in the IAS group at 20 mg/kg was markedly inhibited by 60.6 % (P = 0.0007) compared with the vehicle-treated MIA group, and the anti-collagen type II antibody level in the IAS group was reduced in a dose-dependent manner. IAS (20 mg/kg) effectively suppressed the induction of inflammation-mediated enzymes (iNOS and COX-2) and pro-inflammatory cytokines (TNF-α and IL-1β). IAS treatment also downregulated the NF-κB level and increased the IκB-α level in the MIA- induced osteoarthritis rat model.
  
  
  CONCLUSIONS
  SHINBARO inhibited PGE2 and anti-type II collagen antibody production and modulated the balance of inflammatory enzymes, mediators, and cytokines in the MIA-induced osteoarthritis rat model.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea ; Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 135-896 Republic of Korea.
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Pyee
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
authors.forename: Tae Jun
authors.initials: TJ
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
authors.forename: Hyen Joo
authors.initials: HJ
authors.lastname: Park
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 135-896 Republic of Korea.
authors.forename: Joon-Shik
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 135-896 Republic of Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 135-896 Republic of Korea.
authors.forename: In-Hyuk
authors.initials: IH
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
keywords: Intra-articular administration; Monosodium iodoacetate-induced osteoarthritis; SHINBARO pharmacopuncture