RESUMEN
OBJECTIVE: To investigate the therapeutic efficacy of Tiaobu Feishen formulae (TBFS) on cigarette smoke-induced inflammation in vitro using lipopolysaccharide (LPS)-induced and cigarette smoke extract (CSE)-induced NCI-H292 cells. METHODS: We evaluated the inhibitory effects of Bufei Jianpi formula (BJF), Bufei Yishen formula (BYF), and Yiqi Zishen formula (YZF) on the expressions of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-8, matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloprotease (TIMP)-1, and superoxide dismutase (SOD) in H292 cells stimulated with LPS or CSE. Their related transcription factors and signaling pathways were also analyzed. RESULTS: BJF, BYF, and YZF significantly inhibited the LPS- or CSE-induced expressions of TNF-α, IL-8, MMP-9, TIMP-1, and SOD in H292 cells, and suppressed the activation of transcription factors including nuclear transcription factor (NF)-κB, activator protein (AP)-1, and signal transducers and activators of transcription (STAT) 3 and their corresponding pathways, including NF-κB, mitogen-activated protein kinase (MAPK), STAT3, and peroxisome proliferator-activated receptor (PPAR). CONCLUSION: BJF, BYF, and YZF effectively suppressed inflammatory responses, protease-antiprotease imbalance, and oxidative stress induced by LPS and CSE, an effect that was closely associated with the inhibition of the NF-κB, MAPK, STAT3, and PPAR pathways.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/efectos de los fármacos , Pulmón/inmunología , Fumar/tratamiento farmacológico , Composición de Medicamentos , Medicamentos Herbarios Chinos/química , Células Epiteliales/metabolismo , Humanos , Interleucina-8/genética , Interleucina-8/inmunología , Pulmón/efectos de los fármacos , FN-kappa B/genética , FN-kappa B/inmunología , Humo/efectos adversos , Fumar/efectos adversos , Fumar/genética , Fumar/inmunología , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
We investigated the inhibitory effects of Platycodon grandiflorum root-derived saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1 chemokine secretion in bronchoalveolar lavage fluid. Also, ovalbumin-increased MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-κB activation, leukocytes recruitment, and mucus secretion were inhibited by CKS treatment. Moreover, the active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC mRNA expression (from 2.1 ± 0.2 to 1.1 ± 0.1) by inhibiting NF-κB activation (from 2.3 ± 0.2 to 1.2 ± 0.1) via Akt (from 3.7 ± 0.3 to 2.1 ± 0.2) (p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA suppressed the development of respiratory inflammation, hyperresponsiveness, and remodeling by reducing allergic responses, and they may be potential herbal drugs for allergen-induced respiratory disease prevention.
Asunto(s)
Antiinflamatorios/administración & dosificación , Pulmón/inmunología , Platycodon/química , Saponinas/administración & dosificación , Triterpenos/administración & dosificación , Animales , Línea Celular , Citocinas/genética , Citocinas/inmunología , Femenino , Humanos , Pulmón/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/inmunología , Ratones , Ratones Endogámicos ICR , Mucina 5AC/genética , Mucina 5AC/inmunología , Ovalbúmina/efectos adversos , Raíces de Plantas/química , Acetato de Tetradecanoilforbol/efectos adversos , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/inmunologíaRESUMEN
The antiangiogenic activity of Tinospora cordifolia was studied using in vivo as well as in vitro models. In vivo antiangiogenic activity was studied using B16F10 melanoma cell-induced capillary formation in animals. Intraperitoneal administration of the extract at a concentration of 20 mg/kg significantly inhibited the tumour directed capillary formation induced by melanoma cells. Analysis of the serum cytokine profile showed a drastic increase of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, granulocyte monocyte-colony stimulating factor (GM-CSF) and the direct endothelial cell proliferating agent vascular endothelial cell growth factor (VEGF) in the angiogenesis-induced control animals. Administration of Tinospora extract could differentially regulate these cytokine's elevation. The differential regulation is further evidenced by the increased production of antiangiogenic agents IL-2 and tissue inhibitor of metalloprotease-1 (TIMP-1) in the B16F10-injected, extract-treated animals. Moreover, using an in vitro rat aortic ring assay, it was observed that the extract at nontoxic concentrations inhibited the production of proangiogenic factors from B16F10 melanoma cells. Direct treatment of the extract also inhibits the microvessel outgrowth from the aortic ring. Hence, the observed antiangiogenic activity of the plant T. cordifolia is related, at least in part, to the regulation of the levels of these cytokines and growth factors in the blood of the angiogenesis-induced animal.