The Mechanisms of Sai-rei-to, a Herbal Drug, in the Treatment of Experimental Colitis

Abstract

Purpose: Current medical management of IBD consists of aminosalicylats (ASAs), steroids, and immunosuppressant therapies including azathioprine, and recently TNF-α antibody therapy has also been used. But treatment with these drugs reduces immunity which may be a trigger for adverse events including infection. Sai-rei-to (SRT), a type of kampo medicine (Japanese herbal medicine), is a compound drug made from the crude extracts of various medicinal plants. These plants and extracts have been reported to have an antiinflammatory action. Recently in Japan, the administration of SRT was shown to reduce the amount of steroid administration required for IBD patients. But the mechanisms of the effect of this drug for IBD are unknown. In this study, we demonstrated the effect of SRT on colonic epithelial cell proliferation and apoptosis in rats with TNBS-induced experimental colitis. Methods: SRT, prednisolone (PSL) and 5-ASA (ASA) were administered in various combinations to TNBS rats for 4 weeks. After the rats were sacrificed, any inflammatory change of the colonic mucosa was studied using Matt's classification. The cell proliferation of colonic mucosa was studied the BrdU uptake, and apoptosis cells were stained by Tunel method. Results: The treatment of SRT, PSL and ASA alone significantly reduced colonic inflammation (TNBS control:39.75±1.26, vs. SRT:34.33±1.09, PSL:31.11±1.89, ASA:33.57±1.26) and there was no significant difference on the inflammation between these drugs. PSL administration significantly decreased the number of BrdU-labeled cells (TNBS control:4.66±1.1, vs. PSL:3.44±2.1), but SRT and ASA did not influence the number of BrdU-labeled cells (SRT:4.63±1.1, ASA:4.64±3.2). Both ASA and SRT administration increased the number of total cells in colonic pits (TNBS control:42.61±21.8, ASA:57.11±13.7, SRT:74.34±19.9). In the SRT+ASA group, administration of SRT further increased the number of total cells which had already been increased by ASA treatment (SRT+ASA:72.64±22.7). SRT and ASA treatment alone increased the number of cells above the proliferative zone (TNBS control:24.8±17.3, vs. SRT:56.63±26.3, ASA:39.19±17.8). ASA, PSL and SRT alone significantly decreased the number of apoptosis cells (TNBS control:9.53±2.17, vs. ASA:1.52±0.29, PSL:1.62±0.6, SRT:0.4±0.18). In the SRT+ASA group (ASA:1.52±0.29, vs. SRT+ASA:0.36±0.05) administration of SRT further decreased apoptosis cells which had been decreased by ASA. Conclusion: The treatment of SRT alone decreased colonic inflammation similar to PSL and ASA. SRT reduced both the colonic cells above the PZ zone and the apoptosis cells. From these data, the effect of SRT treatment for IBD is not an inducer of proliferation, and reduces and protects the desquamated colonic epithelial cells.