Kim Won Kyung, Chung Hwa-Jin, Pyee Yuna, Choi Tae Jun, Park Hyen Joo, Hong Ji-Young, Shin Joon-Shik, Lee Jin Ho, Ha In-Hyuk, Lee Sang Kook
College of Pharmacy, Seoul National University, Seoul, 151-742 Republic of Korea.
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.
Chin Med. 2016 Apr 11;11:17. doi: 10.1186/s13020-016-0089-6. eCollection 2016.
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.
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.
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.
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.
SHINBARO是一种用于治疗炎症性病变和骨骼疾病的精制草药配方。本研究旨在探讨关节内注射SHINBARO的抗骨关节炎活性，并确定其在碘乙酸钠（MIA）诱导的骨关节炎大鼠模型中的潜在分子机制。
雄性Sprague-Dawley大鼠右膝髌下韧带内单次关节内注射MIA。随后，大鼠每天用生理盐水、SHINBARO和双氯芬酸治疗一次，共21天。用生理盐水而非MIA治疗的大鼠作为对照组。通过微计算机断层扫描以及苏木精-伊红和番红O固绿染色观察MIA诱导的骨关节炎大鼠模型股骨的组织学变化。使用商业试剂盒测量MIA诱导的骨关节炎大鼠模型中PGE2和抗II型胶原抗体的血清水平。通过蛋白质印迹分析测定软骨组织中炎症酶（iNOS、COX-2）、促炎细胞因子（TNF-α、IL-1β）和炎症介质（NF-κB、IκB）的蛋白质水平。
20mg/kg的SHINBARO关节内给药（IAS）显著抑制了骨体积/总体积的下降，比载体处理的MIA组高28%（P = 0.0001）。与载体处理的MIA组相比，IAS（2、10和20mg/kg）治疗分别使物体值的平均数显著恢复，百分比变化分别增加了13.5%（P = 0.147）、27.5%（P = 0.028）和44.5%（P = 0.031）。与载体处理的MIA组相比，20mg/kg的IAS组中PGE2的血清水平显著降低了60.6%（P = 0.0007），并且IAS组中抗II型胶原抗体水平呈剂量依赖性降低。IAS（20mg/kg）有效抑制了炎症介导酶（iNOS和COX-2）和促炎细胞因子（TNF-α和IL-1β）的诱导。在MIA诱导的骨关节炎大鼠模型中，IAS治疗还下调了NF-κB水平并提高了IκB-α水平。
在MIA诱导的骨关节炎大鼠模型中，SHINBARO抑制了PGE2和抗II型胶原抗体的产生，并调节了炎症酶、介质和细胞因子的平衡。
