RESUMO
Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 µg/mL) and GA (10 µg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-kB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects.
Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ácido Gálico/farmacologia , Basófilos/efeitos dos fármacos , Basófilos/metabolismo , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Quimiocinas/biossíntese , Dexametasona/farmacologia , Humanos , Interleucina-33 , Interleucina-6/biossíntese , Interleucinas/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Paeonia , Fosforilação/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Danshen and gegen (D&G) have long been used in treatment of angina and other cardiac symptoms in Chinese materia medica. Recent pharmacological studies suggest their therapeutic values. We aimed to evaluate the efficacy and safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary prevention. METHODS: One hundred (100) consecutive coronary patients (mean age 58 +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g) or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured using ultrasound. RESULTS: Baseline characteristics were similar between the 2 groups. After 24 weeks and compared with baseline, there were no significant changes in blood pressures, blood hematological and biochemical profiles, or folate and homocysteine levels in both groups, but there was a mild decrease in low density lipoprotein (LDL) cholesterol in both groups (p < 0.05). Brachial FMD improved during D&G (p < 0.001) and less so during placebo treatment (p < 0.05), while improvement in carotid IMT was observed only in the D&G group (p < 0.05). After open-label D&G treatment for 6 more months (n = 45), further improvement in both brachial FMD (p < 0.0001) and carotid IMT (p < 0.0001) was observed. Eight (8) adverse events were reported-6 during placebo and 2 during D&G treatment-requiring treatment termination in 2 patients (on placebo). CONCLUSIONS: D&G adjunctive treatment in coronary patients was well tolerated and effective in improving vascular function and structure. These two herbs may become a novel agent for secondary prevention.
Assuntos
Doença das Coronárias/terapia , Endotélio Vascular/efeitos dos fármacos , Fitoterapia , Preparações de Plantas/uso terapêutico , Pueraria , Salvia miltiorrhiza , Vasodilatadores/uso terapêutico , Artéria Braquial/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Túnica Íntima/efeitos dos fármacos , Túnica Média/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) are two herbs used in traditional Chinese medicine, most commonly for their putative cardioprotective and anti-atherosclerotic effects. In this study, we investigated the effect of a preparation of these herbs on two key processes in the early stages of atherosclerosis; macrophage lipid loading and monocyte adhesion to endothelial cells. Human monocyte derived macrophages (HMDMs) were treated with 0.1-1.0 mg/ml of the herbal mixture in aqueous buffers and loaded with acetylated LDL (AcLDL) (50 microg/ml) for 72 h, and analyzed for cholesterol (C) and cholesteryl esters (CE), via HPLC. Human endothelial cell monolayers were also treated with 0.1-1.0 mg/ml of the herbal mixture and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were assessed via ELISA. Compared to control conditions, the herbal mixture induced a significant dose-related decrease in the total cholesterol (free and esterified) in the HMDMs (p<0.001 by ANOVA). By contrast, the herbs also induced an increase in ICAM-1 expression (p<0.001) and monocyte adhesion at higher concentrations (p<0.05). In conclusion, treatment of cells with this preparation of Danshen and Gegen, a commonly used Chinese health supplement, results in a dose-related suppression of AcLDL uptake by human macrophages, and an increase in the level of ICAM-1 expression and adhesion of monocytes to endothelial cells. These herbs therefore show the ability to modulate key early events in atherosclerosis.