Inhibitory effects of a new iridoid, patridoid II and its isomers, on nitric oxide and TNF-alpha production in cultured murine macrophages.
Patridoids I, II and IIA, are new iridoids isolated from the whole plants of Patrinia saniculaefolia. These compounds were examined by assessing their effects on the production of tumor necrosis factor-alpha (TNF-alpha) as well as by investigating the expression of two enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in the lipopolysaccharide (LPS)-stimulated murine macrophage-like cell line, Raw 264.7. Among them, patridoid II consistently inhibited nitric oxide (NO) and TNF-alpha production in a dose-dependent manner, with IC (50) values of 14.1 and 17.6 microM, respectively. Western Blotting probed with specific anti-iNOS antibodies showed that the decrease in the quantity of the NO product was accompanied by a decrease in the iNOS protein level. However, all three patridoids did not affect the COX-2 protein expression level in the LPS-stimulated macrophages. In addition, the C-5 isomer of patridoid II, patridoid I, only slightly affected the production of NO. Moreover, the C-3 isomer of patridoid II, patridoid IIA, did not inhibit proinflammatory cytokines and NO production. These results suggest that the orientations of the C-3 and C-5 methoxy groups in the patridoids have a significant role in the expression of their biological activity.
Ju
Hye Kyung
HK
College of Pharmacy, Yeungnam University, Gyongsan, Korea.
Moon
Tae Chul
TC
Lee
Eunkyung
E
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; D004305:Dose-Response Relationship, Drug; D039823:Iridoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D032405:Patrinia; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D039823:Iridoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C479942:patridoid II; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse