Downregulation of iNOS expression in rat mesangial cells by special extracts of Harpagophytum procumbens derives from harpagoside-dependent and independent effects
Autor: | C. Erdelmeier, Egon Koch, K.F. Beck, M. Kaszkin, S. Kusch, J. Pfeilschifter, D. Loew |
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Rok vydání: | 2005 |
Předmět: |
Pharmaceutical Science
Down-Regulation Nitric Oxide Synthase Type II Pharmacology Nitric Oxide Harpagophytum Antioxidants Nitric oxide chemistry.chemical_compound Downregulation and upregulation Drug Discovery medicine Animals Glycosides Cells Cultured Pyrans chemistry.chemical_classification Kidney biology Dose-Response Relationship Drug Chemistry Plant Extracts Anti-Inflammatory Agents Non-Steroidal NF-kappa B Glycoside NFKB1 biology.organism_classification Glomerular Mesangium Rats Nitric oxide synthase Dose–response relationship medicine.anatomical_structure Complementary and alternative medicine Biochemistry biology.protein Molecular Medicine Nitric Oxide Synthase Interleukin-1 |
Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 11(7-8) |
ISSN: | 0944-7113 |
Popis: | Special extracts from the roots of Harpagophytum procumbens (Devil's Claw) are used in the supportive treatment of inflammatory diseases, and the iridoid derivative harpagoside is thought to be the active principle. To investigate, whether Harpagophytum extracts may also be useful therapeutics in the treatment of inflammatory kidney diseases, we studied the effects of two different extracts containing 8.9% (extract 1) and 27% harpagoside (extract 2), respectively, on IL-1beta-induced nitric oxide (NO) formation as well as transcriptional regulation of inducible NO synthase (iNOS) in rat renal mesangial cells. We observed a concentration-dependent suppression of nitrite formation by about 80%, which was due to an inhibition of iNOS expression. Moreover, a reduction of iNOS promoter activity and nuclear NF-kappaB translocation was observed, indicating that the extracts interfere with the transcriptional activation of iNOS. Three further Harpagophytum extracts containing about 2% harpagoside did not inhibit NO formation suggesting, that only extracts with a high harpagoside content elicit iNOS inhibition. However, pure harpagoside was only inhibitory at concentrations between 0.3 and 1 mg/ml, which is much higher than the harpagoside content present in an effective concentration of the total extracts. Moreover, a harpagoside-free extract 1 also markedly inhibited iNOS expression, indicating that other extract constituents are involved in this effect. Extract 1 exerted a strong antioxidative effect, whereas no such effect could be demonstrated for harpagoside. Together, these data show that special Harpagophytum extracts may represent potential antiinflammatory drugs in the treatment of glomerular inflammatory diseases. |
Databáze: | OpenAIRE |
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