ABSTRACT
Paeonol, the main active component isolated from the root of Paeonia suffruticosa, has been reported to have anti-inflammatory properties. However, the effects of paeonol on osteoarthritis (OA) remain unclear. The aim of this study was to investigate the anti-inflammatory effects and mechanism of paeonol in IL-1ß-induced human OA chondrocytes as well as mice OA models. Human OA chondrocytes were pretreated with different concentrations of paeonol 2 h prior to IL-1ß (10 ng/mL) stimulation for 24 h. Nitric oxide (NO) production was determined by Griess method. The levels of prostaglandin E2 (PGE2), matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 were assessed by ELISA. Inducible nitric oxide synthase (INOS), COX-2, and PI3K/Akt/NF-κB-related signaling molecules production were measured by Western blot. In vivo, mice OA models were established by destabilization of the medial meniscus. One month after surgery, mice in paeonol-treated group were given intraperitoneal injection of paeonol in 30 mg/kg every day, while mice of vehicle-treated group were injected with DMSO under the same conditions. Hematoxylin and eosin as well as Safranin-O staining were applied to assess the severity of cartilage lesions. The results showed that pretreatment with paeonol could inhibit IL-1ß-induced NO and PGE2 production. Meanwhile, the overproduction of INOS, COX-2, MMP-1, MMP-3, and MMP-13 were also reversed by paeonol. Moreover, paeonol was found to inhibit IL-1ß-induced NF-κB activation, PI3K, and AKT phosphorylation. In vivo, treatment with paeonol exhibited less cartilage degradation and lower Osteoarthritis Research Society International scores in mice OA models. In conclusion, these results suggest that paeonol may be a potential therapeutic agent in the treatment of OA.
Subject(s)
Acetophenones/therapeutic use , Chondrocytes/pathology , Osteoarthritis/drug therapy , Acetophenones/pharmacology , Animals , Cartilage/drug effects , Cartilage/metabolism , Cells, Cultured , Humans , Inflammation/drug therapy , Interleukin-1beta , Mice , NF-kappa B/metabolism , Osteoarthritis/chemically induced , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To study the effectiveness of retinoic acid on induction of osteoporotic rats treated by either alendronate or qianggu capsules and co-administration. METHODS: Sixty-five female SD rats were treated with retinoic acid 80 mg x kg(-1) x d(-1) by gastric lavage for 15 days. Then 5 rats were confirmed cases of osteoporosis and the remaining 60 were randomly divided into 4 groups 15 each: (1) control group with NS 8 ml x kg(-1) x w(-1); (2) alendronate group with alendronate 40 mg x kg(-1) x w(-1); (3) qianggu group with qianggu capsules 90 mg x kg(-1) x d(-1); (4) co-medicated group with alendronate 40 mg x kg(-1) x w(-1) and qianggu capsules 90 mg x kg(-1) x d(-1). Five rats in each group were sacrificed at week 2, 4 and 6 respectively to carry out the biomechanic tests, histopathologic examination and bony callus volume calculation. RESULTS: Biomechanical properties of femur changed significantly after the treatment by alendronate or qianggu capsules and co-medication as compared with that of NS after 4 weeks (P < 0.05); the bony callus were larger when treated by alendronate (P < 0.05) and smaller by qianggu capsules (P > 0.05); the bone trabecula formed and rebuilding were slower by alendronate and quicker by qianggu capsules. CONCLUSION: Alendronate or qianggu capsules and co-medication can improve biomechanical properties of femur by retinoic acid on induction of osteoporotic rats. Qianggu capsules can improve bone union.