Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial-mesenchymal transition.

BACKGROUND: Pulmonary fibrosis (PF) is a fatal inflammatory disease with limited effective strategies. Epithelial-mesenchymal transition (EMT) is a pivotal origin of myofibroblasts that secrete extracellular matrix (ECM) in the development of PF. High mobility group box 1 (HMGB1), one of the mediators of inflammation, has been proved abnormal activation in the pathogenesis of PF. AIM: The present study was aimed to investigate the potential effects of total glycoside of Yupingfeng (YPF-G), the natural compound extracted from Yupingfeng san, on HMGB1 activation and EMT in bleomycin-induced PF, which was a serious disease of respiratory system. METHODS: The Sprague-Dawley (SD) rat model of PF was duplicated by intratracheal instillation of bleomycin (5 mg kg(-1)). After that, YPF-G (5, 10 mg kg(-1)) and prednisone (5 mg kg(-1)) were separately administered intragastrically, and then the rats were killed at days 14 and 28, respectively. Hematoxylin and eosin and Masson's trichrome staining were performed to assess the histopathologic level of lung tissues, western blotting and the common kits were utilized to investigate the hallmarks molecule expression of ECM and EMT, and the level of HMGB1 in lung tissues and serum. RESULTS: We found that both dose of YPF-G markedly reduced bleomycin-induced alveolitis and PF in rats. Besides, the levels of HMGB1, laminin, hyaluronic acid, and hydroxyproline were effectively reduced. Meanwhile, the increased protein expression of HMGB1 and the mesenchymal markers including vimentin and alpha-smooth muscle actin, and the decreased protein expression of epithelial marker E-cadherin were dramatically inhibited after YPF-G treatment. CONCLUSION: Our results demonstrated that YPF-G could ameliorate bleomycin-induced PF by reducing HMGB1 activation and reversing EMT.

Total Glucosides of Danggui Buxue Tang Attenuate BLM-Induced Pulmonary Fibrosis via Regulating Oxidative Stress by Inhibiting NOX4.

Pulmonary fibrosis (PF) is a serious chronic lung disease with unknown pathogenesis. Researches have confirmed that oxidative stress which is regulated by NADPH oxidase-4 (NOX4), a main source of reactive oxygen species (ROS), is an important molecular mechanism underlying PF. Previous studies showed that total glucosides of Danggui Buxue Tang (DBTG), an extract from a classical traditional Chinese herbal formula, Danggui Buxue Tang (DBT), attenuated bleomycin-induced PF in rats. However, the mechanisms of DBTG are still not clear. We hypothesize that DBTG attenuates PF through regulating the level of oxidative stress by inhibiting NOX4. And we found that fibrosis indexes hydroxyproline (HYP) and type I collagen (Col-I) were lower in DBTG groups compared with the model group. In addition, the expression of transforming growth factor-ß1 (TGF-ß1) and expression of alpha smooth muscle actin (α-SMA) were also much more decreased than the model group. For oxidative stress indicators, DBTG blunted the decrease of superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and the increase in malondialdehyde (MDA), 8-iso-prostaglandin in lung homogenates. Treatment with DBTG restrained the expression of NOX4 compared to the model group. Present study confirms that DBTG inhibits BLM-induced PF by modulating the level of oxidative stress via suppressing NOX4.

Total extract of Yupingfeng attenuates bleomycin-induced pulmonary fibrosis in rats.

Yupingfeng is a Chinese herbal compound used efficaciously to treat respiratory tract diseases. Total glucosides of Yupingfeng have been proven effective in anti-inflammation and immunoregulation. Nevertheless, the role of total extract of Yupingfeng (YTE) in pulmonary fibrosis (PF), a severe lung disease with no substantial therapies, remains unknown. Present study was conducted to elucidate the anti-fibrotic activity of YTE. The rat PF model was induced by intratracheal administration of bleomycin (BLM, 5 mg/kg), and YTE (12 mg/kg/d) was gavaged from the second day. At 14 and 28 days, the lungs were harvested and stained with H&E and Masson's trichrome. The content of hydroxyproline (HYP) and type I collagen (Col-I) were detected, while the protein expression of high-mobility group box 1 (HMGB1), transforming growth factor-beta 1 (TGF-ß1), Col-I and α-smooth muscle actin (α-SMA) were analyzed by immunohistochemistry or Western blot. As observed, YTE treatment attenuated the alveolitis and fibrosis induced by BLM, reduced the loss of body weight and increase of lung coefficient. Meanwhile, YTE strongly decreased the levels of HYP and Col-I, and reduced the over-expression of HMGB1, TGF-ß1, Col-I and α-SMA. In conclusion, YTE could ameliorate BLM-induced lung fibrosis by alleviating HMGB1 activity and TGF-ß1 activation, suggesting therapeutic potential for PF.