Abstract
Andrographis paniculata (Burm. f.) Wall. ex Nees (AP) is a medicinal herb widely used in many Asian countries. Andrographolide, the best-characterised bioactive compound in AP, has been shown to have beneficial effects against atherosclerosis. However, there is little information about the effects and underlying mechanisms of the whole AP plant on the development of atherosclerosis. To address this question, we treated apolipoprotein E-deficient mice (on a cholesterol-enriched diet) with AP decoction via dietary supplementation. The biological mechanisms were studied in mouse primary peritoneal macrophages treated with crude serum preparations isolated from normal rats receiving vehicle or AP decoction treatment. We demonstrated that AP significantly reduced the plaque area in both thoracic and abdominal aortas in mice. In macrophage cells, genome-wide mRNA sequencing revealed that AP reversed ~ 70% of the genes responsive to lipopolysaccharides. Further bioinformatics analysis indicated that AP inhibited type I interferon (IFN) signalling. In mouse aortas and lipopolysaccharides-challenged macrophages, we confirmed that AP downregulated the expression of a panel of genes comprising the core modules in the type I IFN signalling. In particular, western blot experiments in macrophage cells demonstrated that AP significantly reduced the total protein level of signal transducer and activator of transcription 1 (STAT1), while IFN-β-induced STAT1 phosphorylation was not changed. In conclusion, given the established pathogenic effects of type I IFN in atherosclerosis, our results suggest that inhibition of the type I IFN signalling in macrophages is partly involved in the anti-atherogenic effects of Andrographis paniculata.