Effect of two different groups of Chinese medicines on nitric oxide production by mouse macrophage-like cells

In Vivo. 2004 Nov-Dec;18(6):771-8.

Abstract

Seven Chinese medicines were investigated for their ability to modify nitric oxide (NO) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells, in comparison with their radical intensity and scavenging activity. LPS significantly stimulated the NO production by Raw 264.7 cells. Three Chinese medicines, Shosaiko-to, Hange-shashin-to and Sairei-to (tentatively classified as Group I), significantly reduced the extracellular concentration of NO in the LPS-stimulated cells, slightly below their cytotoxic concentrations. On the other hand, another four Chinese medicines, Byakko-ka-ninjin-to, Hochu-ekki-to, Juzen-taiho-to and Ninjin-yoei-to (tentatively classified as Group II), showed similar effects, but required higher concentrations due to the co-existence of both the inhibitors and stimulators for NO production by activated macrophages. Western blot analysis demonstrated that LPS stimulated the expression of inducible NO synthase (iNOS) at both protein and mRNA levels, and that Sairei-to reduced the LPS-induced iNOS expression more potently than did Juzen-taiho-to. ESR spectroscopy shows that Group I medicines generally produced higher amounts of radicals under alkaline condition, and scavenged superoxide (produced by hypoxanthine-xanthine oxidase reaction) and NO (produced by NOC-7, NO generator) more potently than Group II medicines. These data support the classification of Chinese medicines into two groups: Group I and Group II. The net inhibition of NO production by Group I medicines may be the summation of the radical scavenging activity and the inhibition of iNOS expression due to higher cytotoxicity. Group II medicines showed lower cytotoxicity, lower radical intensity, lower radical scavenging activity, but higher stimulation activity for NO production by macrophages than Group I, suggesting their possible application for immunopotentiation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / classification
  • Drugs, Chinese Herbal / pharmacology*
  • Free Radical Scavengers / classification
  • Free Radical Scavengers / pharmacology*
  • Gene Expression / drug effects
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects*
  • Macrophage Activation / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Medicine, Chinese Traditional*
  • Mice
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • RNA, Messenger / metabolism

Substances

  • Drugs, Chinese Herbal
  • Free Radical Scavengers
  • Lipopolysaccharides
  • RNA, Messenger
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse