Cryptotanshinone reverses the epithelial‐mesenchymal transformation process and attenuates bleomycin‐induced pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial pneumonia that causes pulmonary tissue damage and functional impairment. To investigate the effects of cryptotanshinone on pulmonary fibrosis, the expression of NIH/3T3, HPF, and rat primary pulmonary fibroblasts was measured and found to be inhibited by CPT in a timeand concentration-dependent manner, and the upregulation of α-SMA expression in NIH/3T3 and HPF cells, which had been stimulated by TGFβ-1, was decreased after CPT administration. We observed that CPT could reverse the increase in α-SMA expression and vimentin and the decrease in E-cad expression in A549 cells, which had been induced by 5 ng/mL TGFβ-1, indicating that CPT has inhibitory effects in the EMT process. A BLM-induced pulmonary fibrosis model was established in C57BL/6 mice. The lung coefficient and hydroxyproline content increased significantly in the BLM-induced group and were decreased in the CPT-treated group. The expression levels of collagen-I and α-SMA and the phosphorylation level of Stat3 were significantly increased, and CPT treatment decreased these levels. Furthermore, the results from the flow cytometry analysis indicated that, in lung tissues, the frequencies of MDSCs, macrophages, DCs and T cells were considerably increased in the BLMinduced group, while CPT treatment reduced these immunocyte populations.

Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial–Mesenchymal Transition

“…For instance, EMT and glomerulosclerosis in rats with chronic kidney disease were suppressed by JAK/STAT signaling pathway ( Zhao et al, 2019 ), and cyclosporine-A-induced renal fibrosis was ameliorated by chrysin by the inhibition of TGF-beta-induced EMT ( Nagavally et al, 2021 ). In addition, the PI3K-Akt signaling pathway, a major regulator of anti-inflammation, has been reported to prevent renal fibrosis by attenuating renal tubular epithelial cell–mesenchymal transition ( Hu et al, 2021 ; Zhang Q et al, 2020 ; Wang et al, 2019 ). In line with this, JPYSF inhibited the inflammation via suppression of the NF–kappa B signaling pathway ( Lu et al, 2018 ).…”

The antioxidant N-acetylcysteine promotes immune response and inhibits epithelial-mesenchymal transition to alleviate pulmonary fibrosis in chronic obstructive pulmonary disease by suppressing the VWF/p38 MAPK axis

“…Our initial observations revealed that COPD was accompanied with promoted cell migration and invasion, decreased E-cadherin expression, the ratio of CD3 + , CD4 + , CD8 + and CD4 + /CD8 + T lymphocytes, and levels of IgG, IgA, and IgM, and elevated N-cadherin expression and levels of IL-6 and TNF-α. An autoimmune component related to bronchial epithelial cell damage is possibly implicated in COPD progression and the presence of IgG and IgA is involved in COPD (Zhang et al 2020 ). A recent study has also proved that ETM is a leading factor for COPD with decreased E‐cadherin expression and elevated levels of α‐SMA and collagen type I (Wang et al 2019 ).…”

Mechanism of Fei-Xian Formula in the Treatment of Pulmonary Fibrosis on the Basis of Network Pharmacology Analysis Combined with Molecular Docking Validation

“…Of these core components, quercetin, betasitosterol, baicalein, luteolin, ellagic acid, wogonin, naringenin, tanshinone IIa, stigmasterol, and cryptotanshinone from DS, TR, CS, TD, QG, and MHD in FXF were the most significant in line with the degree values. Some of them were suggested previously to postpone pulmonary fibrosis course and improve the symptoms [40][41][42][43]. Besides, PTGS2, NOS2, CDK2, GSK3B, CCNA2, PPARG, MAPK14, CASP3, BCL2, and RELA ranked the top 10 places based on the degree value.…”