Inducible nitric oxide synthase inhibitors of Chinese herbs III. Rheum palmatum.
In this paper, the effects of bioactive compounds of Rheum palmatum L. on the inhibition of NO production from RAW 264.7 cells were explored. Seven main anthraquinone derivatives were isolated from the root of R. palmatum, and of these, emodin and rhein significantly inhibited nitrite production from lipopolysaccharide (LPS)-activated RAW 264.7 cells. The IC(50) values for inhibition of nitrite production by emodin and rhein were 60.7 and 67.3 microM, respectively. After iNOS enzyme activity was stimulated by LPS for 12 h, treatment with emodin or rhein at 20 microg/ml for 18 h did not significantly inhibit NO production. The data show that the inhibitory activity of emodin and rhein is not due to direct inhibition of iNOS enzyme activity. However, expression of iNOS and the COX-2 protein was inhibited by emodin in LPS-activated RAW 264.7 cells, and PGE(2) production was reduced. Rhein also inhibited LPS-induced iNOS protein expression, but not COX-2 or PGE(2) production. On the other hand, inhibition effects on NO production from RAW 264.7 cells were enhanced and cytotoxic effects decreased by co-treatment with emodin and rhein. In conclusion, emodin and rhein are major iNOS inhibitors of R. palmatum and may possibly serve as bioactive substances for anti-inflammation effects.
Wang
Ching-Chiung
CC
Graduate Institute of Pharmacognosy Science, Taipei Medical University, Taipei, Taiwan, ROC.
Huang
Yi-Ju
YJ
Chen
Lih-Geeng
LG
Lee
Lain-Tze
LT
Yang
Ling-Ling
LL
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D004642:Emodin / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008565:Membrane Proteins; D051379:Mice; D006899:Mixed Function Oxygenases / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D008517:Phytotherapy; D018517:Plant Roots / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D012250:Rheum / Q000737:chemistry*
D000880:Anthraquinones; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D006899:Mixed Function Oxygenases; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D004642:Emodin; C020491:rhein