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  • Title: Enantiomers of higenamine inhibit LPS-induced iNOS in a macrophage cell line and improve the survival of mice with experimental endotoxemia.
    Author: Park JE, Kang YJ, Park MK, Lee YS, Kim HJ, Seo HG, Lee JH, Hye Sook YC, Shin JS, Lee HW, Ahn SK, Chang KC.
    Journal: Int Immunopharmacol; 2006 Feb; 6(2):226-33. PubMed ID: 16399627.
    Abstract:
    The importance of development of single enantiomers (optically pure isomers) of chiral molecules has been recognized and manifested in countless pharmaceutical and biological advancement. (RS)-(+/-)-Higenamine (racemic mixture), an active ingredient of Aconite tuber, has been shown to have antioxidant activity along with inhibitory action of iNOS expression in various cells. In the present study, the effects of each enantiomer of higenamine [(S)-(-)-higenamine and (R)-(+)-higenamine] were investigated in comparison with the effects of racemic mixture [(RS)-(+/-)-higenamine] on iNOS expression and NO production in RAW 264.7 cells activated with LPS. In addition, the effects of higenamine enantiomers on the survival rates were also investigated using mice, in which each test compound was injected (i.p.) 90 min prior to LPS. All three forms of higenamine inhibited iNOS expression and reduced NO production with IC50 of 26.2, 86.3, and 53.4 microM, for (S)-, (R)-, and (RS)-higenamine, respectively. (S)-higenamine also significantly reduced serum NOx level and increased survival rates in LPS-treated mice. In contrast, (R)-isomer only showed tendency to increase the survival rates which was not statistically significant when compared to LPS-treated controls. Taken together, it was concluded that (S)-higenamine may be more beneficial than (R)-enantiomer in diseases associated with iNOS over-expression, such as septic shock.
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