Bufei Yishen Formula Inhibits the Cell Senescence in COPD by Up-Regulating the ZNF263 and Klotho Expression.

Background: Bufei Yishen formula (BYF) is an effective prescription for the clinical treatment of chronic obstructive pulmonary disease (COPD). However, the molecular mechanism by which it exerts its pharmacological effects remains to be explored. Methods: The human bronchial cell line BEAS-2B was treated with cigarette smoke extract (CSE). Cellular senescence markers were detected by Western blot and ELISA. Potential transcription factor of klotho was predicted using JASPAR and USCS databases. Results: CSE induced cellular senescence with intracellular accumulation of cellular senescence biomarkers (p16, p21 and p27) and increased secretion of senescence-related secretory phenotypic (SASP) factors (IL-6, IL-8, and CCL3). In contrast, BYF treatment inhibited CSE-induced cellular senescence. CSE suppressed the transcription, expression and secretion of klotho, whereas BYF treatment rescued its transcription, expression and secretion. CSE downregulated the protein level of ZNF263, whereas BYF treatment rescued the expression of ZNF263. Furthermore, ZNF263-overexpressing BEAS-2B cells could inhibit CSE-induced cellular senescence and SASP factor secretion by upregulating the expression of klotho. Conclusion: This study revealed a novel pharmacological mechanism by which BYF alleviates clinical symptoms of COPD patients, and regulating ZNF263 and klotho expression may be beneficial to the treatment and prevention of COPD.

Effects of Huatan Tongluo decoction on vascular endothelial growth factor receptor 2 expression in synovial tissues of rats with collagen-induced arthritis.

OBJECTIVE: To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis. METHODS: Forty specific pathogen-free Wistar rats were selected, and 10 were randomly selected as the control (group 1). The remaining rats were injected intradermally with emulsified type II bovine collagen at the tail base and back, followed by a booster 7 d post first immunization. After establishing collagen-induced arthritis (CIA), rats were randomly divided into three groups (n = 10). The rats were treated orally for 30 d as follows: group 1, saline; group 2, model (saline); group 3, tripterygium polyglycoside (TP; 7.81 mg/kg, positive control); group 4, Huatan Tongluo decoction (HTTL; 7.5 g/kg). Body weight, ankle swelling and arthritis index were measured over the course of the study. The rats were sacrificed 30 d after treatment. Morphological changes in the synovium were observed by hematoxylin and eosin staining. Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor (VEGF) and VEGFR2 protein levels were measured by immunohistochemistry. VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction. RESULTS: Compared with the model group, a significantly lower arthritis index was observed in the positive control group (P < 0.05) and HTTL group (P < 0.01), after treatment. Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening. Furthermore, VEGF mRNA, and VEGFR2 protein and mRNA levels were significantly downregulated (P < 0.05) in the treatment groups. CONCLUSION: Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.