title: Inhibitory effects of a new iridoid, patridoid II and its isomers, on nitric oxide and TNF-alpha production in cultured murine macrophages.
abstract: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyongsan, Korea.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Ju
authors.forename: Tae Chul
authors.initials: TC
authors.lastname: Moon
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Lee
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
authors.forename: Ren-Bo
authors.initials: RB
authors.lastname: An
authors.forename: KiHwan
authors.initials: K
authors.lastname: Bae
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Hyun Pyo
authors.initials: HP
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: 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
chemical_list: 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