The Bufei Nashen pill inhibits the PI3K/AKT/HIF-1 signaling pathway to regulate extracellular matrix deposition and improve COPD progression

Ethnopharmacological relevance: According to the theory and practice of traditional Chinese medicine (TCM), chronic obstructive pulmonary disease (COPD) can be classified as "cough," "dyspnea," or "lung distention disease." Bufei Nashen pill (BFNSP) is a classic Chinese herbal formula with certain activity against the above syndromes. FNSP has previously been shown to improve clinical symptoms (cough, lumbar and knee weakness, tinnitus) in patients with occupationally related interstitial lung disease.

Aim of the study: There is a lack of convincing evidence supporting the use of BFNSP for the treatment of COPD. This study aimed to investigate the effect of BFNSP on COPD and explore its underlying mechanisms.

Materials and methods: Liquid chromatography-mass spectrometry (LC/MS) was used to analyze the main components of BFNSP and BFNSP-containing serum. A COPD rat model was generated, and the rats were treated with different doses of BFNSP. Lung function indices were analyzed by a pulmonary function testing system, and lung histopathology was assessed by HE staining and scanning electron microscopy. The levels of TGF-β1, IL-6, IL-8, IL-1β, MMP3, MMP-9, and TIMP1 in BALF and the levels of MMP3, MMP-9, TIMP1, and HA in serum were detected by ELISA. Immunohistochemical staining was performed to determine the expression of Col-I, Col-III, and LN in lung tissues. RT‒qPCR was performed to detect the mRNA expression of PI3K, Akt, HIF-1α, MMP-9, TGF-β1, TIMP1, and ERK1/2 in lung tissue, and Western blotting was performed to detect the protein expression of PI3K, p-PI3K, Akt, p-Akt, HIF-1α, MMP-9, TGF-β1, TIMP1, and p-ERK1/2 in lung tissue. In addition, in vitro cellular assays were performed for validation.

Results: The results showed that BFNSP effectively improved the functional status of pulmonary ventilation, attenuated pathological damage in lung tissue, inhibited the release of inflammatory factors, reduced extracellular matrix deposition, and inhibited the activation of the PI3K/Akt/HIF-1 signaling pathway in lung tissue in COPD rats (P<0.05) and may alleviate COPD progression by inhibiting the PI3K/Akt/HIF-1 signaling pathway.

Conclusion: BFNSP inhibits the PI3K/Akt/HIF-1 signaling pathway to regulate extracellular matrix deposition and improve COPD progression.

Bufei Nashen pill; PI3K/AKT/HIF-1 signaling pathway; chronic obstructive pulmonary disease; extracellular matrix.