Chun-Fei Wang1, Jia-Rui Yuan2, Dong Qin2, Jun-Fei Gu2, Bing-Jie Zhao2, Li Zhang2, Di Zhao2, Juan Chen2, Xue-Feng Hou1, Nan Yang2, Wei-Quan Bu3, Jing Wang2, Chao Li4, Gang Tian4, Zi-Bo Dong4, Liang Feng5, Xiao-Bin Jia6. 1. Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. 2. Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. 3. Department of Pediatrics, Jiangsu Integrative Hospital of Chinese Traditional and Western Medicine, Jiangsu, Nanjing 210028, PR China. 4. Jumpcan Pharmaceutical Co., Ltd, Taixing 225400, PR China. 5. Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. Electronic address: wenmoxiushi@163.com. 6. Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui, Hefei 230012, PR China. Electronic address: jxiaobin2005@hotmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Tauroursodeoxycholic acid (TUDCA), one of the main ingredients from bear gall which hold "Clearing heat and detoxification, Removing liver fire for improving eyesight" functions, is formed by the conjugation of ursodeoxycholic acid (UDCA) with taurine. However, the limited information of TUDCA on protecting diabetic retinopathy (DR) has been known. The present study was conducted to evaluate the protection of TUDCA on high glucose-induced human retinal microvascular endothelial cells (HRMECs) dysfunction and streptozotocin (STZ)-induced diabetic retinopathy (DR) rats and the possible mechanism underlying was also explored. MATERIALS AND METHODS: The proliferation of high glucose-induced HRMECs was determined by MTT assay. DR rats' model was established by an administration of high-glucose-fat diet and an intraperitoneal injection of STZ (30mg/kg). The cell supernatant and rats' serum were collected for the assays of NO content by ELISA kits. Retinas were stained with hematoxylin and eosin (HE) to observe pathological changes. Immunohistochemical assay was applied to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in rat retinas. Furthermore, western blot analysis was carried out to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in high glucose-induced HRMECs. RESULTS: After treating with TUDCA, high glucose-induced HRMECs proliferation could be significantly inhibited. TUDCA (5.0μM, 25.0μM and 125.0μM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500mg/kg/d and 250mg/kg/d) also decrease NO content in serum of DR rats. Additionally, both immunocytochemistry analysis and western blot analysis showed that the over-expression of ICAM-1, NOS, NF-κB p65 and VEGF were significantly decreased by TUDCA. CONCLUSION: The data indicated that TUDCA could ameliorate DR by decreasing NO content and down-regulating the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF. Thus, our experimental results suggested that TUDCA might be a potential drug for the prevention and treatment of DR.
ETHNOPHARMACOLOGICAL RELEVANCE: Tauroursodeoxycholic acid (TUDCA), one of the main ingredients from bear gall which hold "Clearing heat and detoxification, Removing liver fire for improving eyesight" functions, is formed by the conjugation of ursodeoxycholic acid (UDCA) with taurine. However, the limited information of TUDCA on protecting diabetic retinopathy (DR) has been known. The present study was conducted to evaluate the protection of TUDCA on high glucose-induced human retinal microvascular endothelial cells (HRMECs) dysfunction and streptozotocin (STZ)-induced diabetic retinopathy (DR) rats and the possible mechanism underlying was also explored. MATERIALS AND METHODS: The proliferation of high glucose-induced HRMECs was determined by MTT assay. DR rats' model was established by an administration of high-glucose-fat diet and an intraperitoneal injection of STZ (30mg/kg). The cell supernatant and rats' serum were collected for the assays of NO content by ELISA kits. Retinas were stained with hematoxylin and eosin (HE) to observe pathological changes. Immunohistochemical assay was applied to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in rat retinas. Furthermore, western blot analysis was carried out to examine the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF in high glucose-induced HRMECs. RESULTS: After treating with TUDCA, high glucose-induced HRMECs proliferation could be significantly inhibited. TUDCA (5.0μM, 25.0μM and 125.0μM) could decrease NO content in high glucose-induced HRMECs. Furthermore, TUDCA (500mg/kg/d and 250mg/kg/d) also decrease NO content in serum of DR rats. Additionally, both immunocytochemistry analysis and western blot analysis showed that the over-expression of ICAM-1, NOS, NF-κB p65 and VEGF were significantly decreased by TUDCA. CONCLUSION: The data indicated that TUDCA could ameliorate DR by decreasing NO content and down-regulating the protein expression of ICAM-1, NOS, NF-κB p65 and VEGF. Thus, our experimental results suggested that TUDCA might be a potential drug for the prevention and treatment of DR.
Authors: Eleni Beli; Yuanqing Yan; Leni Moldovan; Cristiano P Vieira; Ruli Gao; Yaqian Duan; Ram Prasad; Ashay Bhatwadekar; Fletcher A White; Steven D Townsend; Luisa Chan; Caitlin N Ryan; Daniel Morton; Emil G Moldovan; Fang-I Chu; Gavin Y Oudit; Hartmut Derendorf; Luciano Adorini; Xiaoxin X Wang; Carmella Evans-Molina; Raghavendra G Mirmira; Michael E Boulton; Mervin C Yoder; Qiuhong Li; Moshe Levi; Julia V Busik; Maria B Grant Journal: Diabetes Date: 2018-04-30 Impact factor: 9.337