ABSTRACT
The in vitro anti-inflammatory effects of seven known lignans and one dihydrochalcone isolated from the leaves of two Lauraceae species (Pleurothyrium cinereum and Ocotea macrophylla), were evaluated through the inhibition of COX-1, COX-2, 5-LOX and the aggregation of rabbit platelets induced by PAF, AA and ADP. (+)-de-4"-O--methylmagnolin 4 was found to be a potent COX-2/5-LOX dual inhibitor and PAF-antagonist (COX-2 IC50 2.27 µM; 5-LOX IC50 5.05 µM; PAF IC50 2.51 µM). However, all compounds exhibited an activity at different levels, indicating good anti-inflammatory properties to be considered in further structural optimization studies.
Os efeitos anti-inflamatórios in vitro de sete conhecidos lignanos e uma dihidrocalcona isolados das folhas de duas espécies da família Lauraceae (Pleurothyrium cinereum e Ocotea macrophylla) foram avaliados por meio da inibição da COX1, COX-2, 5-LOX e agregação de plaquetas de coelhos induzida por PAF, AA e ADP. A (+)-4"-O-metilmagnolina-4 foi encontrada como mais potente inibidora tanto da COX-2 quanto de 5-LOX e antagonista de PAF (COX-2 IC50 2,27 µM; 5- LOX IC50 5,05 µM; PAF IC50 2,51 µM). Entretanto, todos compostos mostram uma atividade em intensidades diferentes, indicando boas propriedades anti-inflamátorias a serem consideradas para futuros estudos de modificações e otimização estruturais.
Subject(s)
Animals , Rabbits , Anti-Inflammatory Agents/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Lauraceae/chemistry , Lipoxygenase Inhibitors/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Anti-Inflammatory Agents/isolation & purification , Cyclooxygenase 1 , Cyclooxygenase Inhibitors/isolation & purification , /pharmacology , Lipoxygenase Inhibitors/isolation & purification , Platelet Aggregation Inhibitors/isolation & purificationABSTRACT
The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C), a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC) and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of 10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.
Subject(s)
Animals , Humans , Cell Physiological Phenomena/drug effects , Crotalid Venoms/chemistry , Disintegrins/pharmacology , /drug effects , Platelet Aggregation Inhibitors/pharmacology , Bothrops , Cell Adhesion/drug effects , Cell Adhesion/physiology , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Disintegrins/isolation & purification , Gene Expression/drug effects , /physiology , Platelet Aggregation Inhibitors/isolation & purificationABSTRACT
Rubia cordifolia is clinically used for the purification of blood by the physicians of the Indian System of Medicine. For the first time, the effect of the partially purified fraction of this whole plant has been studied on rabbit platelets. It inhibits the platelet aggregation induced by PAF (platelet activating factor) but not thrombin. It also inhibits the binding of 3H-PAF to the platelets in the dose-dependent manner. Thus it appears that R. cordifolia inhibits action of PAF at its receptor level either by it's blocking or by desensitization.