In vitro and in vivo anti-inflammatory effects of andrographolide.
Andrographolide - the major active principle isolated from the plant Andrographis paniculata, has been shown to possess a strong anti-inflammatory activity. The possibility that the drug may affect asthmatic inflammation, through inhibition of the relevant inflammatory cytokines, has not been explored. The purpose of this study was, firstly, to investigate the ability of andrographolide to inhibit the release of inflammatory cytokines in vitro in a model of non-specific inflammation and subsequently to determine whether such effect can also be exerted in vivo in allergic lung inflammation. LPS-induced TNF-alpha and GM-CSF release from mouse peritoneal macrophages was inhibited by andrographolide in a concentration-dependent manner. The concentration of the drug producing 50% inhibition was 0.6 microM for TNF-alpha and 3.3 microM for GM-CSF. The maximal inhibition achieved (at 50 microM) was 77% and 94%, respectively, for the two cytokines. The drug was as efficacious as dexamethasone, but about 8-12 times less potent. The drug also suppressed LPS-induced expression of mRNA for the two cytokines, suggesting that this effect may contribute to the mechanism underlying its anti-inflammatory effects. In the in vivo study, intra-peritoneal treatment of ovalbumin-immunized and nasally-challenged mice with andrographolide significantly inhibited the elevation of bronchoalveolar fluid (BAF) levels of TNF-alpha and GM-CSF in a dose-dependent manner, with 30 mg/kg producing an inhibition of 92% and 65% of the cytokines, respectively) and almost completely abolishing the accumulation of lymphocytes and eosinophils. These results provide evidence that andrographolide is an effective anti-inflammatory drug that is active in vitro and in vivo, and affects both non-specific as well as antigen/antibody-dependent lung inflammation. Thus, andrographolide has the potential to be used in a variety of inflammatory conditions, including allergic lung inflammation.
Abu-Ghefreh
Ala'a A
AA
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
Canatan
Halit
H
Ezeamuzie
Charles I
CI
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C030419:andrographolide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin