Zhi-Tao Feng1, Tong Yang2, Xiao-Qiang Hou3, Han-Yu Wu2, Jia-Teng Feng2, Bing-Jin Ou2, San-Jin Cai2, Juan Li4, Zhi-Gang Mei5. 1. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, 443002, China; Shenzhen Institute of Geriatrics, Shenzhen, Guangdong, 518020, China; The Institute of Rheumatology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, 443003, China. 2. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, 443002, China. 3. The Institute of Rheumatology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei, 443003, China. 4. Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: lj40038@126.com. 5. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, 443002, China. Electronic address: meizhigang@ctgu.edu.cn.
Abstract
OBJECTIVE: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. METHODS: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD). RESULTS: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups. CONCLUSION: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.
OBJECTIVE: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. METHODS:Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD). RESULTS: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups. CONCLUSION:SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.
Authors: Xuan Xia; Brian H May; Anthony Lin Zhang; Xinfeng Guo; Chuanjian Lu; Charlie C Xue; Qingchun Huang Journal: Evid Based Complement Alternat Med Date: 2020-04-28 Impact factor: 2.629