Andrographolide affects Th1/Th2/Th17 responses of peripheral blood mononuclear cells from ulcerative colitis patients

摘要

Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 mu g/ml). Andrographolide decreased interferon gamma, interleukin (IL)-23 and IL-17A, however it increased IL-4 in a dose-dependent manner, as indicated by ELISA assay. Andrographolide treatment resulted in a decreased percentage of T helper (Th)1 and Th17 cells and an increased proportion of Th2 cells, as demonstrated by flow cytometry analysis. T-bet (a Th1-specific transcription factor) and RAR-related orphan receptor gamma t (key transcription factor of Th17 cells) expression was decreased, but GATA-3 (Th2 lineage-specific transcription factor) expression was increased following andrographolide treatment as indicated by western blot analysis. These results demonstrated the inhibitory effects on Th1/Th17 responses and the promoting effects on Th2 responses of andrographolide. Experiments on IL-23-treated PBMCs from healthy donors revealed similar effects of andrographolide on Th1/Th2/Th17 responses. In summary, these results suggest that andrographolide may be an effective candidate for the treatment of IL-23-mediated diseases.