RESUMO
Intestinal α-glucosidase performs a physiologically vital function in the digestive process of dietary carbohydrates. Administration of an α-glucosidase inhibitor may retard the digestion and absorption of carbohydrates. Consequently, the rise in postprandial blood glucose could be suppressed. This study developed a novel technology, called "after flowing through immobilized receptor (AFTIR)," for targeting components in herbal medicines with α-glucosidase-suppressing capability. As a result, we reveal that the AFTIR system is a highly-efficient drug screening platform, capable of purifying and identifying active components with α-glucosidase-suppressing capability in herbal medicines.
Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Carboidratos da Dieta/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/química , Glicemia/metabolismo , Inibidores Enzimáticos/farmacologia , Medicina Herbária , Hipoglicemiantes/farmacologia , Plantas Medicinais/química , Período Pós-PrandialRESUMO
PURPOSE: Cynarin, a potential immunosuppressant that blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells, was found in Echinacea purpurea by a new pharmaceutical screening method: After Flowing Through Immobilized Receptor (AFTIR; Dong et al., J Med Chem, 49: 1845-1854, 2006). This Echinacea component is the first small molecule that is able to specifically block "signal 2" of T-cell activation. METHODS: In this study, we used the AFTIR method to further confirm that cynarin effectively blocked the binding between CD80 of B-cells and CD28 of T-cells, and provide details of its mechanism of action. RESULTS: The experimental results showed that cynarin blocked about 87% of the CD28-dependent "signal 2" pathway of T-cell activation under the condition of one to one ratio of T-cell and B-cell in vitro. Theoretical structure modeling showed that cynarin binds to the "G-pocket" of CD28 (Evans et al., Nat Immunol, 6:271-279, 2005), and thus interrupts the site of interaction between CD28 and CD80. CONCLUSIONS: These results confirm both that AFTIR is a promising method for screening selective active compounds from herbal medicine and that cynarin has great potential as an immuno-suppressive agent.
Assuntos
Antígenos CD28/metabolismo , Cinamatos/farmacologia , Echinacea , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Antígeno B7-1/metabolismo , Sítios de Ligação , Antígenos CD28/química , Complexo CD3/metabolismo , Cinamatos/química , Cinamatos/isolamento & purificação , Técnicas de Cocultura , Simulação por Computador , Relação Dose-Resposta a Droga , Echinacea/química , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Interleucina-2/metabolismo , Células Jurkat , Modelos Moleculares , Estrutura Molecular , Conformação Proteica , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Linfócitos T/imunologiaRESUMO
Investigations were carried out to evaluate the therapeutic properties of the seeds and leaves of Moringa oleifera Lam as herbal medicines. Ethanol extracts showed anti-fungal activities in vitro against dermatophytes such as Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis. GC-MS analysis of the chemical composition of the essential oil from leaves showed a total of 44 compounds. Isolated extracts could be of use for the future development of anti-skin disease agents.
Assuntos
Antifúngicos/farmacologia , Moringa oleifera/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Antifúngicos/química , Fungos/efeitos dos fármacos , Óleos Voláteis/química , Extratos Vegetais/química , Folhas de Planta/química , Óleos de Plantas/química , Sementes/químicaRESUMO
AFTIR (after flowing through immobilized receptor) is a novel method for screening herbal extracts for pharmaceutical properties. Using AFTIR, we identified Cynarin in Echinacea purpurea by its selective binding to chip immobilized CD28, a receptor of T-cells, which is instrumental to immune functioning. The results of surface plasma resonance show that binding between immobilized CD28 and Cynarin is stronger than the binding between CD28 and CD80, a co-stimulated receptor of antigen presenting cells. Cynarin's function was verified by its ability to downregulate CD28-dependent interleukin-2 (IL-2) expression in a T-cell culture line. AFTIR offers promise as an efficient screening method for herbal medicines.
