Combination therapy of tanshinone IIA and puerarin for pulmonary fibrosis via targeting IL6‐JAK2‐STAT3/STAT1 signaling pathways

Abstract

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.

The longitudinal and regional analysis of bleomycin-induced pulmonary fibrosis in mice by microcomputed tomography

“…Through the semi-quantification of micro-CT images obtained from 66 mice, we observed that the distribution pattern of fibrosis was predominantly located in the mid-to upper- and dorso-centric regions of the lungs 21 days after bleomycin administration, consistent with prior published studies [ [4] , [5] , [6] , 8 , [13] , [14] , [15] , [16] , [17] ]. This distribution pattern may be attributable to the fact that bleomycin primarily settles in the mid-to upper-lungs along with the airflow of breathing.…”

“…Despite the development of micro-CT quantification methods for BIPF mouse models over the past decade [ 4 ], this technique has not been routinely employed for monitoring changes in lung fibrosis. Typically, micro-CT is used only at the endpoint of a study [ [5] , [6] , [7] , [8] ], which makes it challenging to ascertain whether the mice had comparable degrees of fibrosis at the study's start before any therapeutic interventions (no early than 7–10 days post-bleomycin) [ 9 ]. This is largely due to the fact that manual tools for micro-CT image analysis are time-consuming and labor-intensive [ 10 ].…”

From Basic Research to Clinical Practice: Considerations for Treatment Drugs for Silicosis

“…Moreover, sulforaphane, dihydroartemisinin, melatonin and ginkgo biloba extract have been found to reduce oxidative stress to exert anti-pulmonary-fibrosis effects [99][100][101][102][103]. Similarly, the total extract of Yupingfeng and the combination of tan IIA and puerarin can exert antifibrotic effects by regulating the PI3K/AKT/mTOR signaling pathway and JAK/STAT signaling pathway [104][105][106]. As for regulating signaling pathways related to EMT, asiatic acid and oridonin inhibit the expression of TGF-β1 in lung tissue, accompanied by a decrease in Col-I, Col-III, α-SMA and TIMP-1, as well as inactivation of Smads and ERK1/2 [107,108].…”

Preparation of tanshinone IIA self-soluble microneedles and its inhibition on proliferation of human skin fibroblasts

“…It has good effects of anti-inflammation, anti-infection and regulating immunity. Some earlier studies have investigated the effects of TSA on the proliferation reduction dose-dependently index of abnormally proliferating fibroblasts in HS ( Xue et al, 2021 ). However, as a kind of fat-soluble strong phenanthrene quinone compound, TSA is difficult to penetrate the active epidermis of human body.…”