A preliminary study of the immunomodulation by radix Angelica sinensis (Chinese danggui) and heparin in experimental colitis

Background & Aims: In the pharmacotherapy of inflammatory bowel diseases, we are searching for agents that are target-specific in their antiinflammatory actions and also possess promising immunomodulating properties. Heparin, a polysaccharide with anticoagulant activity, had been shown to improve severe colitis. Besides, the polysaccharide fraction of radix Angelica sinensis (Chinese Danggui) extract (AS) was reported to have immunomodulatory effects. It is interesting to determine whether the active compounds from AS could exert immunomodulating action that is similar to that of heparin during the intervention of colitis development. Thus, by using an animal colitis model, we attempt to investigate the effects of heparin, and AS on colitis formation and the modulation of various cytokines in the colon. Methods: Colitis was induced experimentally in male SD rats by enema administration of the hapten dinitrobenzenesulfonic acid. The rats then received therapeutic treatments twice daily on the three consecutive days, comprising intracolonic unfractionated heparin (500 U/kg or 2.8 mg/kg), intracolonic or oral AS (100, 200 mg/kg). The animals were sacrificed on the fourth day following hapten administration. Colonic damage, colonic myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities, colonic levels of leukotriene B₄ (LTB4), TNF-a, IL-1ß and IL-10 had been measured. In addition, RT-PCR had also been conducted to observe the co-regulation of cytokine gene expressions by the therapeutic agents. Results: AS (both i.c. & p.o.) and heparin had shown significant protection against the hapten-induced macroscopic colonic damage, which was consistent with the drop in colonic MPO activity. Intracolonic AS and heparin had induced significant decline in colonic iNOS activity and reduction in LIB₄, TNF-a and 1Lß levels, while concomitantly caused an increase in colonic IL-10 level. Furthermore, corresponding modulation in colonic TNF-a and IL-10 mRNA expressions by intracolonic AS and heparin had also been demonstrated. Alternately, oral AS and heparin did not exhibit a strong and coherent effect in regulating the proinflammatcny mediators and cytokines in the colon. Conclusion: The orthodox drug heparin and extract from the traditional Chinese medicine danggui could act in concert to establish an effective therapeutic regimen to treat colitis diseases via immunomodulation of cytokines and the resulting regulation of proinflammatory mediators.