Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils

Koichi Yamashita, Huangwei Lu, Jincai Lu, Guang Chen, Takeshi Yokoyama, Yasuhiro Sagara, Masanobu Manabe, Hiroyuki Kodama

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Abstract

Background: The roots of Anemone raddeana are used in Chinese folk medicine for curing rheumatism and neuralgia. Methods: The three triterpenoids lupeol, betulin and betulinic acid were isolated from ethanol extracts of the roots of A. raddeana. The effect of these triterpenoids on superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils was investigated. Results: The superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly suppressed by betulin and lupeol depending on the concentration of the triterpenoids. The suppressive effect of betulinic acid was low. The phorbol 12-myristate 13-acetate (PMA)-induced superoxide generation was suppressed by betulin in a concentration-dependent manner, but not by lupeol and betulinic acid. In contrast, the superoxide generation induced by arachidonic acid (AA) was suppressed by lupeol, while betulin and betulinic acid weakly enhanced the AA-induced superoxide generation. Lupeol and betulin suppressed tyrosyl phosphorylation of a 45.0-kDa protein in fMLP-treated human neutrophils in parallel to the suppression of fMLP-induced superoxide generation, but betulinic acid did not. Lupeol, betulin and betulinic acid showed no hemolytic effect even at a concentration of 500 μmol/l. Conclusions: Lupeol and betulin suppress superoxide generation by preventing tyrosyl phosphorylation of a 45.0-kDa protein in human neutrophils, and may have pharmaceutical applications.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalClinica Chimica Acta
Volume325
Issue number1-2
DOIs
Publication statusPublished - Nov 1 2002
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

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