Inhibitory effects of nardostachin on nitric oxide, prostaglandin E2, and tumor necrosis factor-alpha production in lipopolysaccharide activated macrophages.
Nardostachin, which is an iridoid isolated from Patrinia saniculaefolia, was examined by assessing its effect on the production of tumor necrosis factor-alpha (TNF-alpha) and expression of 2 enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. This compound consistently inhibited the production of nitric oxide (NO) and TNF-alpha production in a dose-dependent manner, with respective IC(50) values of 12.3 and 16.2 microM. The decrease in quantity of NO products was accompanied by a decrease in the iNOS protein level, as assessed by Western blotting probed with specific anti-iNOS antibodies. In addition, this compound also reduced the COX-2 protein expression level and the attendant PGE(2) production in LPS-stimulated macrophages. These results suggest that nardostachin may be useful for inhibiting the production of inflammatory mediators such as TNF-alpha, NO and PGE(2) in inflammatory diseases.
Ju
Hye Kyung
HK
College of Pharmacy, Yeungnam University, Gyongsan, Korea.
Baek
Suk-Hwan
SH
An
Ren-Bo
RB
Bae
KiHwan
K
Son
Kun Ho
KH
Kim
Hyun Pyo
HP
Kang
Sam Sik
SS
Lee
Sung Ho
SH
Son
Jong Keun
JK
Chang
Hyeun Wook
HW
D000818:Animals; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D032405:Patrinia; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018514:Plant Structures; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D004224:Diterpenes; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C056050:nardostachin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone