Effective Component Compatibility of Bufei Yishen Formula III Alleviates Pulmonary Vascular Inflammation in COPD: Via...

Chronic inflammation of the lungs can affect pulmonary vascular remodeling in chronic obstructive pulmonary disease (COPD). The Bufei Yishen formula (BYF) and Effective-compound combination of BYF III (ECC-BYF III) ameliorate lung histopathological injury and remodeling, but the mechanism remains unclear. This study aimed to observe the effects of ECC-BYF III on pulmonary vascular inflammation in COPD and to elucidate its detailed mechanism.

In vivo, COPD rat model was established through cigarette smoke exposure (CSE) combined with repeated infections of Klebsiella pneumoniae. Rats were randomly treated with ECC-BYF III (5.5 mg/kg, once a day) or doxofylline (36 mg/kg, once a day) for eight weeks. In vitro, Human umbilical vein endothelial cells (HUVECs) and human monocyte leukemia cells (THP-1) were induced with 10 μg/mL LPS for 24h. The pulmonary function, histopathology, inflammatory factor levels, immunoblotting results were evaluated.

Compared with the model group, ECC-BYF III significantly improved the lung function, alleviated pulmonary artery inflammation and relieved pulmonary vascular remodeling in COPD rats. At the molecular level, ECC-BYF III down-regulated VEGF₁₆₅/P38 MAPK signaling pathway. In the inflammatory model of HUVEC induced by LPS, 35 and 70μg/mL ECC-BYF III significantly decreased the levels of tumor necrosis factor -α (TNF-α), interleukin-1β (IL-1β) and Endothelin-1 (ET-1) mRNA, and increased the expression of endothelial nitric oxide synthase (eNOS) mRNA. In addition, ECC-BYF III also inhibited VEGF₁₆₅/P38 MAPK pathway in LPS-induced HUVEC and THP-1/HUVEC co-cultured inflammatory models.

Our findings demonstrate that ECC-BYF III can improve pulmonary vascular remodeling in COPD rats, and its key pharmacodynamic mechanism involves the inhibition of the VEGF₁₆₅/P38 MAPK pathway, thereby reducing inflammatory infiltration.