ZhuYang TongBi decoction ameliorates pulmonary fibrosis by degrading TGFBR via CAV1

Context: Pulmonary fibrosis is a widely occurring chronic interstitial lung disease. Traditional Chinese medicine, particularly ZhuYang TongBi (ZYTB) decoction, has been used to treat pulmonary fibrosis for more than a decade.

Objective: This study aimed to explore the pharmacological effects, mechanisms and active ingredients of ZYTB decoction in the treatment of pulmonary fibrosis.

Materials and methods: First, we identified the components of ZYTB decoction in serum using mass spectrometry and performed network pharmacology analysis. Then, we treated mice with a pulmonary fibrosis model with ZYTB decoction for 7 and 14 days. We comprehensively evaluated the therapeutic effect of ZYTB decoction based on lung CT scans, histopathological examination, and the expression of fibrosis marker proteins. Furthermore, we used Western blotting, quantitative Real-Time PCR, immunohistochemistry, immunofluorescence, and small interfering RNA (siRNA) to elucidate the mechanism of ZYTB decoction in treating pulmonary fibrosis.

Results: We identified 29 active ingredients in serum samples and ZYTB decoction. These active ingredients effectively reduced pulmonary fibrosis, bronchial damage, inflammatory infiltration, and Collagen deposition in mice. ZYTB decoction inhibited the expression of fibronectin, Collagen I, and α-SMA both in vitro and in vivo. Network pharmacology analysis and protein expression studies verified that ZYTB decoction enhanced CAV1 expression and inhibited the expression of TGFR and SMAD2/3. Knockdown of CAV1 blocked the therapeutic effect of ZYTB decoction on pulmonary fibrosis.

Discussion and conclusions: ZYTB decoction ameliorates pulmonary fibrosis in mice and inhibits epithelial-mesenchymal transition in vitro. This protective effect may be related to TGFBR degradation by CAV1.