RESUMEN
In inflammation, the responses to noxious stimuli are controlled by the highly modulated interactions between various immune cells and chemical mediators. The purpose of this study is to evaluate and compare the anti-inflammatory effect of diterpenoids isolated from Andrographis paniculata, including dehydroandrographolide (AP1), andrographolide (AP2) and neoandrographolide (AP3), on the production of inflammatory cytokines and COX activities. Furthermore, the alteration of gene expression involved in this activity was investigated in the most potent compound to elucidate the other possible molecular mechanisms. AP1 (30.1 µM; 10 µg/ml) and AP2 (28.5 µM; 10 µg/ml) markedly inhibited COX-1 in ionophore A23187-induced human platelets. AP2 (28.5 µM) and AP3 (20.8 µM; 10 µg/ml) strongly suppressed the LPS-stimulated COX-2 activity in human blood. In addition, AP2 modulated the level of LPS-induced TNF-α, IL-6, IL-1ß and IL-10 secretion in human blood in a concentration-dependent manner. The results revealed that AP2 exhibited the highest efficacy. Therefore, changes in the levels of mRNA transcripts by AP2 were further measured using human cDNA microarrays. The molecular response to AP2 was complex and mediated by various processes. Among the altered gene expressions, the genes involved in immune and inflammation processes were selectively down-regulated, such as cytokines and cytokine receptors (TNFSF14, TNF, TNFRSF6, and IL1A), chemokines (CCL8 and CXCL11), JAK/STAT signaling (JAK3 and STAT5A), TLRs family (TLR4 and TLR8) and NF-κB (NFKB1). Expression of some genes was validated using RT-PCR. The results demonstrated that AP1, AP2 and AP3 exhibited the anti-inflammatory effect by interfering COX and inflammatory cytokines and the underlying mechanisms of AP2 may be related to down-expression of genes involved in inflammatory cascade.
Asunto(s)
Andrographis/química , Antiinflamatorios no Esteroideos/farmacología , Diterpenos/farmacología , Expresión Génica/efectos de los fármacos , Glucósidos/farmacología , Tetrahidronaftalenos/farmacología , Adulto , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Plaquetas/efectos de los fármacos , Plaquetas/inmunología , Calcimicina/farmacología , Ciclooxigenasa 1/inmunología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/inmunología , Ciclooxigenasa 2/metabolismo , Citocinas/sangre , Citocinas/inmunología , Diterpenos/química , Diterpenos/aislamiento & purificación , Regulación hacia Abajo , Glucósidos/química , Glucósidos/aislamiento & purificación , Humanos , Masculino , Receptores de Citocinas/inmunología , Receptores de Citocinas/metabolismo , Tetrahidronaftalenos/química , Tetrahidronaftalenos/aislamiento & purificación , Receptores Toll-Like/análisis , Receptores Toll-Like/inmunología , Adulto JovenRESUMEN
The ethanolic extract of Kaempferia parviflora (KP) rhizomes dose-dependently relaxed both aortic rings and ileum precontracted with phenylephrine and acethylcholine, respectively.
Asunto(s)
Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Vasodilatadores/farmacología , Zingiberaceae , Acetilcolina , Animales , Aorta/efectos de los fármacos , Aorta/fisiopatología , Relación Dosis-Respuesta a Droga , Humanos , Íleon/efectos de los fármacos , Íleon/fisiopatología , Masculino , Músculo Liso Vascular/fisiopatología , Fenilefrina , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Rizoma , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéuticoRESUMEN
The rhizomes of Kaempferia parviflora (KP) (Zingiberaceae) have been used in Thai traditional medicine for health promotion and for the treatment of digestive disorders and gastric ulcer. This study investigated effect of KP on endothelial function. Studies in human umbilical vein endothelial cells (HUVEC) showed that KP dose-dependently increased nitrite concentrations in culture media after 48 h incubation. eNOS mRNA and protein expression were also enhanced. The induction of eNOS mRNA was detected at 4 h and plateau at 48 h while iNOS expression was not observed. These data demonstrate that KP has a great potential for a supplemental use in vascular endothelial health promotion.
Asunto(s)
Células Endoteliales/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Extractos Vegetales/farmacología , Zingiberaceae/química , Relación Dosis-Respuesta a Droga , Células Endoteliales/metabolismo , Humanos , Medicina Tradicional de Asia Oriental , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/genética , Nitritos/metabolismo , Fitoterapia , Extractos Vegetales/química , Plantas Medicinales/química , ARN Mensajero/efectos de los fármacos , Rizoma , Tailandia , Venas Umbilicales/citología , Venas Umbilicales/metabolismoRESUMEN
Three new dammarane triterpenes, bruguierins A-C (1-3), were isolated from a petroleum ether extract of the flowers of Bruguiera gymnorrhiza. Their structures were determined on the basis of physical and spectroscopic data interpretation. With stably transfected HepG2 cells, the three isolates activated antioxidant response element (ARE luciferase activation) with EC(50) values of 7.8, 9.4, and 15.7 microM, respectively. Bruguierin A (1) also inhibited phorbol ester-induced NFkappaB (nuclear factor-kappaB) luciferase activation with an IC(50) value of 1.4 microM and selectively inhibited cyclooxygenase-2 (COX-2) activity with an IC(50) value of 0.37 microM. Compounds 2 and 3 were not active in these bioassays.
Asunto(s)
Inhibidores de la Ciclooxigenasa 2 , Plantas Medicinales/química , Rhizophoraceae/química , Triterpenos , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Tailandia , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , DamaranosRESUMEN
A new cyclic 4-hydroxy-dithiosulfonate, bruguiesulfurol (1), as well as two known 4-hydroxydithiolane 1-oxides, brugierol (2) and isobrugierol (3) were isolated from the flowers of Bruguiera gymnorrhiza. With stably-transfected HepG2 cells, the three isolates activated antioxidant response element (ARE) luciferase activation with (EC(50)) values of 56.7, 3.7 and 1.8 microM, respectively. Compounds 2 and 3 also inhibited phorbol ester-induced NF-kappaB (nuclear factor-kappaB) luciferase activity with IC (50) values of 85.0 and 14.5 microM, respectively. In addition, compound 2 inhibited enzyme cyclooxygenase-2 (COX-2) activity with an IC(50) value of 6.1 microM. The structures of these isolates were determined by spectral data, and that of compound 1 was confirmed by X-ray crystallographic analysis.
Asunto(s)
Antioxidantes/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Rhizophoraceae , Ácidos Tiosulfónicos/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/uso terapéutico , Línea Celular Tumoral/efectos de los fármacos , Cristalografía por Rayos X , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/uso terapéutico , Flores , Humanos , Concentración 50 Inhibidora , Luciferasas/metabolismo , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Ácidos Tiosulfónicos/administración & dosificación , Ácidos Tiosulfónicos/química , Ácidos Tiosulfónicos/uso terapéuticoRESUMEN
Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy. Many recent studies have shown that DOX toxicity involves generation of reactive oxygen species (ROS). Although protection or alleviation of DOX toxicity can be achieved by administration of antioxidant vitamins such as ascorbic acid and vitamin E, their cardioprotective effect remains controversial. Thus alternative naturally occurring antioxidants may potentially be candidates for antioxidant therapy. In this study, we investigated the antioxidative and cytoprotective effects of Phyllanthus urinaria (PU) against DOX toxicity using H9c2 cardiac myoblasts. The total antioxidant capacity of PU (1 mg/ml) was 5306.75+/-461.62 FRAP value (microM). DOX IC50 values were used to evaluate the cytoprotective effects of PU ethanolic extract (1 or 10 microg/ml) in comparison with those of ascorbic acid (VIT C, 100 microM) and N-acetylcysteine (NAC, 100 microM). PU treatments (1 or 10 microg/ml) dose dependently caused rightward DOX IC50 shifts of 2.8- and 8.5-fold, respectively while treatments with VIT C and NAC increased DOX IC50 by 3.3- and 4.2-fold, respectively. Additionally, lipid peroxidation and caspase-3 activity were parameters used to evaluate cytoprotective effect. All antioxidants completely inhibited cellular lipid peroxidation and caspase-3 activation induced by DOX (1 microM). Endogenous antioxidant defense such as total glutathione (tGSH), catalase and superoxide dismutase (SOD) activity was also modulated by the antioxidants. PU treatment alone dose dependently increased tGSH, and this effect was retained in the presence of DOX. Similar effect was observed in the assessment of catalase and SOD enzyme activity. The nuclear factor kappaB (NFkappaB) transcription factor assay demonstrated that all antioxidants significantly inhibited DOX-induced NFkappaB activation. Our results suggest that PU protection against DOX cardiotoxicity was mediated through multiple pathways and this plant may serve as an alternative source of antioxidants for prevention of DOX cardiotoxicity.
Asunto(s)
Antioxidantes/farmacología , Cardiotónicos/farmacología , Doxorrubicina/toxicidad , Corazón/efectos de los fármacos , Phyllanthus/efectos de los fármacos , Animales , Caspasa 3 , Caspasas/metabolismo , Línea Celular , Peroxidación de Lípido/efectos de los fármacos , FN-kappa B/metabolismo , RatasRESUMEN
The present study quantitatively investigated the antioxidant effects of the aqueous extracts from dried calyx of Hibiscus sabdariffa LINN. (roselle) in vitro using rat low-density lipoprotein (LDL). Formations of the conjugated dienes and thiobarbituric acid reactive substances (TBARs) were monitored as markers of the early and later stages of the oxidation of LDL, respectively. Thus, we demonstrated that the dried calyx extracts of roselle exhibits strong antioxidant activity in Cu(2+)-mediated oxidation of LDL (p<0.05) in vitro. The inhibitory effect of the extracts on LDL oxidation was dose-dependent at concentrations ranging from 0.1 to 5 mg/ml. Moreover, 5 mg/ml of roselle inhibited TBARs-formation with greater potency than 100 microM of vitamin E. In conclusion, this study provides a quantitative insight into the potent antioxidant effect of roselle in vitro.
Asunto(s)
Antioxidantes/farmacología , LDL-Colesterol/metabolismo , Hibiscus , Animales , Antioxidantes/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Masculino , Componentes Aéreos de las Plantas , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , AguaRESUMEN
Doxorubicin is an important and effective anticancer drug widely used for the treatment of various types of cancer but its clinical use is limited by dose-dependent cardiotoxicity. Elevated tissue levels of cellular superoxide anion/oxidative stress are a mechanism by which doxorubicin-induced cardiotoxicity. Selected medicinal plant extracts were tested for their antioxidant capacity and cardioprotective effect against doxorubicin-induced cardiotoxicity. The cardiac myoblasts H9c2 were incubated with the antioxidants ascorbic acid, trolox, N-acetylcysteine or selected medicinal plant extracts including; 1) ethanolic extracts from Curcuma longa L-EtOH Phyllanthus emblica L-EtOH, and Piper rostratum Roxb-EtOH; and 2) water extracts from Curcuma longa L-H2O and Morus alba L-H2O. The cardioprotective effects of these extracts were evaluated by crystal violet cytotoxicity assay. IC50s of doxorubicin were compared in the presence or absence of ascorbic acids, trolox, N-acetylcysteine or plant extracts. Morus alba L-H2O showed the highest antioxidant properties evaluated by ferric reducing/antioxidant power assay. Ascorbic acid and N-acetylcysteine had modest effects on the protection of doxorubicin-induced cytotoxicity while trolox showed insignificant protective effect. All plant extracts protected cardiac toxicity at different degrees except that Curcuma longa L-EtOH had no protective effect. Phyllanthus emblica-EtOH (100 microg/ml) showed the highest cardioprotective effect (approximately 12-fold doxorubicin IC50 increase). The data demonstrate that antioxidants from natural sources may be useful in the protection of cardiotoxicity in patients who receive doxorubicin.