Efficient
therapy of
idiopathic pulmonary fibrosis (IPF) is still a major challenge. The current studies with single-target
drug therapy are the pessimistic approaches due to the complex characteristics of IPF. Here, a combination
therapy of
Tanshinone IIA and
Puerarin for IPF was proposed to alleviate IPF due to their antiinflammatory and anti-fibrotic effects. In vivo, the combination
therapy could significantly attenuate the area of ground glass opacification that was presented by 85% percentile density score of the micro-CT images when compared to single conditions. In addition, the combination
therapy enormously improved the survival rate and alleviated pathological changes
in bleomycin (BLM)-induced IPF mice. By using a wide spectrum of infiltration
biomarkers in immunofluorescence assay in pathological sections, we demonstrate that fewer
IL6 related macrophage infiltration and
fibrosis area after this combination
therapy, and further proved that
IL6-JAK2-STAT3/STAT1 is the key mechanism of the combination
therapy. In vitro, combination
therapy markedly inhibited the fibroblasts activation and migration which was induced by TGF-β1 or/and
IL6 through JAK2-STAT3/STAT1 signaling pathway. This study demonstrated that combination
therapeutic effect of TanIIA and Pue on IPF may be related to the reduced inflammatory response targeting
IL6, which could be an optimistic and effective approach for IPF.