Wenhui Cui1,2, Liucheng Li3, Delin Li4, Xiaoting Mo1,2, Wencheng Zhou1,2, Zhihui Zhang2, Liang Xu4, Ping Zhao4, Lianwen Qi5, Ping Li5, Jian Gao6,7. 1. School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. 2. The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China. 3. Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, China. 4. School of Pharmacy, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei, 230038, Anhui, China. 5. State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Jiangsu, 210009, Nanjing, China. 6. School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. gaojianayfy@163.com. 7. The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China. gaojianayfy@163.com.
Abstract
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.
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.
Entities:
Keywords:
Epithelial–mesenchymal transition; High mobility group box 1; Pulmonary fibrosis; Total glycosides of Yupingfeng