Dehydroandrographolide enhances innate immunity of intestinal tract through up-regulation the expression of hBD-2

Background: Dehydroandrographolide (DA) is one of major active components in the well-known oriental herbal medicine Andrographis paniculata (Burm.f) Nees which belongs to the Acanthaceae family. DA is used for the treatment of infections in China. However, DA has not been found to significantly inhibit bacterial and viral growth directly. The current study investigates the effect of DA on the expression of human β –defensin-2 (hBD-2) in human intestinal epithelial cells and the possible signaling pathways. Methods: Human intestinal epithelial HCT-116 cells were incubated with 1–100 μM DA for 2–24 h. RT–PCR and Western blot were used to assess the expression of hBD-2. The specific inhibitors were used and the levels of phosphorylation of signaling molecules were detected for dissecting the signaling pathways leading to the induction of hBD-2. Results: MTT assay showed there was no obvious cytotoxicity for HCT-116 cells by 1–100 μM DA treatment. RT-PCR and Western blot assays showed that DA (1–100 μM) could up-regulate the expression of hBD-2, and the effect lasted longer than 24 h. By using SB203580 and SB202190 (inhibitors of p38), the enhancement of hBD-2 expression were significantly attenuated. However, inhibitor of ERK and inhibitor of JNK could not block the effect of DA. Furthermore, Western blot found activation of p38 but not ERK and JNK in DA-treated HCT-116 cells. Conclusion: The results suggested that DA enhanced innate immunity of intestinal tract by up-regulating the expression of hBD-2 through the p38 MAPK pathways.