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2.
J Ethnopharmacol ; 110(3): 559-62, 2007 Apr 04.
Article in English | MEDLINE | ID: mdl-17113256

ABSTRACT

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.


Subject(s)
Endothelial Cells/drug effects , Gene Expression Regulation/drug effects , Plant Extracts/pharmacology , Zingiberaceae/chemistry , Dose-Response Relationship, Drug , Endothelial Cells/metabolism , Humans , Medicine, East Asian Traditional , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/drug effects , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type III/drug effects , Nitric Oxide Synthase Type III/genetics , Nitrites/metabolism , Phytotherapy , Plant Extracts/chemistry , Plants, Medicinal/chemistry , RNA, Messenger/drug effects , Rhizome , Thailand , Umbilical Veins/cytology , Umbilical Veins/metabolism
3.
Biol Pharm Bull ; 28(7): 1165-71, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15997091

ABSTRACT

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.


Subject(s)
Antioxidants/pharmacology , Cardiotonic Agents/pharmacology , Doxorubicin/toxicity , Heart/drug effects , Phyllanthus/drug effects , Animals , Caspase 3 , Caspases/metabolism , Cell Line , Lipid Peroxidation/drug effects , NF-kappa B/metabolism , Rats
4.
Basic Clin Pharmacol Toxicol ; 96(1): 80-7, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15667600

ABSTRACT

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.


Subject(s)
Antibiotics, Antineoplastic/antagonists & inhibitors , Antibiotics, Antineoplastic/toxicity , Antioxidants/pharmacology , Cardiotonic Agents/pharmacology , Doxorubicin/antagonists & inhibitors , Doxorubicin/toxicity , Plants, Medicinal/chemistry , Animals , Antioxidants/isolation & purification , Cardiotonic Agents/isolation & purification , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Ferric Compounds/chemistry , HeLa Cells , Humans , Myocytes, Cardiac/drug effects , Oxidation-Reduction , Rats
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