RESUMO
The major pathologic manifestations of rheumatoid arthritis (RA) and osteoarthritis (OA) are joint inflammation and articular cartilage resorption by proinflammatory cytokine-stimulated matrix metalloproteinases (MMPs) and aggrecanases. The Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) is effective for treatment of various types of arthritis. However, mechanisms and targets of its actions are poorly understood. Anti-inflammatory activities of the extracts of this plant were previously attributed to inhibition of cyclooxygenase-2 mRNA and prostaglandin E(2) synthesis. Here, we show that in primary human femoral head osteoarthritic and normal bovine chondrocytes, TWHF partially or completely inhibited mRNA and protein expression of tumor necrosis factor-alpha, interleukin (IL)-1, and IL-17-inducible MMP-3 and MMP-13. This agent also inhibited cytokine-stimulated MMP-3 protein expression in human synovial fibroblasts. A dose range of 2.5 to 10 ng/ml of TWHF was effectively inhibitory for IL-1. Pretreatment for 30 min or 1 h (but not 2-10 h) after IL-1 treatment with TWHF inhibited MMP-3 RNA induction. The inhibitory doses had no adverse effect on the viability of chondrocytes. Mechanistic studies revealed no impact on the activation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase mitogen-activated protein kinases. Instead, TWHF partially inhibited DNA binding capacity of cytokine-stimulated activating protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) transcription factors. Therefore, besides its anti-inflammatory activity, this agent may also be effective in blocking cartilage matrix resorption by MMPs by impairing AP-1 and NF-kappaB binding activities. Thus, TWHF extract contains novel inhibitors of MMP expression that may be of therapeutic potential in arthritis and other conditions associated with increased MMPs.
Assuntos
Condrócitos/efeitos dos fármacos , Citocinas/farmacologia , Medicamentos de Ervas Chinesas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 3 da Matriz/biossíntese , NF-kappa B/antagonistas & inibidores , Fator de Transcrição AP-1/antagonistas & inibidores , Animais , Cartilagem Articular/citologia , Cartilagem Articular/efeitos dos fármacos , Bovinos , Células Cultivadas , Condrócitos/enzimologia , Colagenases/biossíntese , Colagenases/genética , DNA/efeitos dos fármacos , DNA/metabolismo , Interações Medicamentosas , Humanos , Metaloproteinase 13 da Matriz , Metaloproteinase 3 da Matriz/genética , Extratos Vegetais/farmacologia , TripterygiumRESUMO
Juzam (leprosy) is attributed to excessive accumulation, infiltration and dispersal of sauda (burnt humours) throughout the body disturbing the normal temperament of the organs. A variety of causative factors responsible for excessive production or retention of sauda are enumerated. Unani simple plants, animals and minerals and formulations used for the treatment of leprosy are tabulated with recipes, methods of preparation, does and modes of administration.