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DOI: 10.1055/s-2000-8592
Inhibitors of Nitric Oxide Synthesis and TNF-α Expression from Magnolia obovata in Activated Macrophages
Publikationsverlauf
Publikationsdatum:
31. Dezember 2000 (online)
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Abstract
Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) are the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. An activity-guided fractionation of an MeOH extract of stem bark of Magnolia obovata afforded two inhibitors of NO production in lipopolysaccharides (LPS)-activated macrophages by the suppression of i-NOS expression. Their structures were elucidated by spectroscopic methods to be magnolol and honokiol with IC50 values of 16.8 and 6.4 μM, respectively. They also inhibited the production of TNF-α in LPS-activated macrophages. Thus, these compounds may be possible candidates for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-α.
References
- 1 Forstermann U,, Schmidt H H,, Pollock J S,, Sheng H,, Mitchell J A,, Warner T D,, Nakaue M,, Murad F.. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem. Pharmacol.. 1991;; 42 1849-57
- 2 Bredt D S,, Snyder S H.. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. USA. 1990;; 87 682-5
- 3 Lowenstein C J,, Glatt C S,, Bredt D S,, Snyder S H.. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proc. Natl. Acad. Sci. USA. 1992;; 89 6711-5
- 4 Kilbourn R G,, Belloni P.. Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J. Natl. Cancer Inst.. 1990;; 82 772-6
- 5 Kilbourn R G,, Gross S S,, Jubran A,, Adams J,, Griffith O W,, Levi R,, Lodato R F.. N G-Methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: Implications for the involvement of nitric oxide. Proc. Natl. Acad. Sci. USA. 1990;; 87 3629-32
- 6 Thiemermann C,, Vane J.. Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. . Eur. J. Pharmacol.. 1990;; 182 591-5
- 7 Thiemermann C,, Wu C-C,, Szabo C,, Perretti M,, Vane J.. Role of tumour necrosis factor in the induction of nitric oxide synthase in a rat model of endotoxin shock. Br. J. Pharmacol.. 1993;; 110 177-82
- 8 Namba T,, Tsunezuka M,, Hattori M.. Dental caries prevention by traditional Chinese medicines. Planta Medica. 1982;; 44 100-6
- 9 El-Feraly F S,, Li W-S.. Phenolic constituents of Magnolia grandiflora L. seeds. Lloydia. 1978;; 41 442-9
- 10 Lee H J,, Kim N Y,, Jang M K,, Son H J,, Kim K M,, Sohn D H,, Lee S H,, Ryu J-H.. A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible nitric oxide synthase and TNFα in LPS-activated macrophages. Planta Medica. 1999;; 65 104-8
- 11 Green L C,, Wagner D A,, Glogowski J,, Skipper P L,, Wishnok J S,, Tannenbaum S R.. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal. Biochem.. 1982;; 126 131-8
- 12 Chapekar M S,, Zaremba T G,, Kuester R K,, Hitchins V M.. Synergistic induction of tumor necrosis factor alpha by bacterial lipopolysaccharide and lipoteichoic acid in combination with polytetrafluoroethylene particles in a murine macrophage cell line RAW 264.7. J. Biomed. Mater. Res.. 1996;; 31 251-6
- 13 Laemmli U K.. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;; 227 680-5
Prof. Jae-Ha Ryu
College of Pharmacy Sookmyung Women's University
Chungpa-Dong 2-Ka
Yongsa-Ku
Seoul 140-742
Korea
eMail: ryuha@sdic.sookmyung.ac.kr
Telefon: +82-2-714-0745
Fax: +82-2-710-9568