RESUMO
Notoginseng Radix and Rehmanniae Radix Preparata have been widely used traditionally for treating inflammatory diseases. This research studies the therapeutic effects of YH23537, the extracts of Notoginseng Radix and Rehmanniae Radix Preparata, on pain and cartilage degeneration in an experimental osteoarthritis (OA) model. Male Wistar rats were inoculated intra-articularly with 3 mg of monosodium iodoacetate (MIA) in the right intra-articular. Four days later, the animals were administrated orally with YH23537 daily for 24 days. Tactile allodynia and weight bearing were measured. Macroscopic and microscopic observations for articular cartilage were performed at the end of the experiment. Protein expression in the joint was determined by immunohistochemistry. The effects of YH23537 on mRNA levels in chondrocytes stimulated with interleukin (IL)-1ß were analyzed using random polymerase chain reaction. OA induction was confirmed by significant decrease of paw withdrawal latency, paw withdrawal threshold, and weight bearing compared with the normal group at 3 days after MIA injection. The YH23537-treated groups displayed significant increases in pain thresholds and weight bearing throughout the observation period. The damage to articular cartilage was significantly lessened visually and histopathologically by YH23537 treatment. YH23537 suppressed the expression of metalloproteinase-3, nitrotyrosine, IL-1ß and IL-6 increased in OA joints. YH23537 upregulated tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 in IL-1ß-stimulated human OA chondrocytes. The protein levels of the NF-κBp65 and HIF-2α in the joint tissues were reduced by YH23537. YH23537 exerted antinociceptive effects and cartilage protective effects in experimental OA rats by suppressing oxidative injury, inflammatory mediators, and inducing anabolic factors. We suggest that YH23537 may have efficacy for treating OA in humans.
Assuntos
Anti-Inflamatórios/farmacologia , Doenças das Cartilagens/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Panax , Extratos Vegetais/farmacologia , Rehmannia , Administração Oral , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Doenças das Cartilagens/induzido quimicamente , Cartilagem Articular/efeitos dos fármacos , Modelos Animais de Doenças , Iodoacetatos , Masculino , Osteoartrite/induzido quimicamente , Medição da Dor , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Ratos , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenol compound from Curcuma longa L. has been used for centuries as an anti-inflammatory remedy including asthma. Curcumin has been reported to exert an anti-inflammatory effect, in part, through inhibition of the NF-κB pathway. AIM OF THE STUDY: The purposes of this study were to determine whether curcumin inhibits NF-κB-dependent transcription in vitro, and test whether treatment with curcumin reduces allergen-induced airway inflammation and hyper-responsiveness in a mouse model of asthma through inhibition of NF-κB pathway. MATERIALS AND METHODS: The effect of curcumin on NF-κB transcriptional activity was investigated using a cell-based luciferase reporter assay in A549 cells and by measuring inhibitory κBα (IκBα), p65, and p50 levels after exposure of Raw264.7 cells to lipopolysaccharide (LPS). BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and challenged with repeated exposure to aerosolized OVA. The effects of daily administered curcumin (200mg/kg body weight, i.p.) on airway hyper-responsiveness (AHR), inflammatory cell number, and IgE levels in bronchoalveolar lavage (BAL) fluid were analyzed. NF-κB activation in lung tissue was also assessed by Western blot analyses. RESULTS: Curcumin inhibited NF-κB-dependent transcription in reporter assays in A549 cells with an IC(50) of 21.50±1.25µM. Curcumin stabilized IκBα and inhibited nuclear translocation of p65 and p50 in LPS-activated Raw264.7 cells, and curcumin-treated mice showed reduced nuclear translocation of p65 in lung tissue. Treatment with curcumin significantly attenuated AHR and reduced the numbers of total leukocytes and eosinophils in BAL fluid. Infiltration of inflammatory cells and mucus occlusions in lung tissue were significantly ameliorated by treatment with curcumin, which also markedly decreased the level of IgE in BAL fluid. CONCLUSION: Curcumin attenuates the development of allergic airway inflammation and hyper-responsiveness, possibly through inhibition of NF-κB activation in the asthmatic lung tissue. Our results indicate that curcumin may attenuate development of asthma by inhibition of NF-κB activation.