Ming-hua Zhang1, Liang Feng2, Mao-mao Zhu3, Jun-fei Gu4, Jun Jiang5, Xu-dong Cheng4, Shu-ming Ding4, Chan Wu4, Xiao-bin Jia6. 1. Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; Department of Pharmaceutics, Jiangsu University, Jiangsu, Zhenjiang 212013, PR China. 2. Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. Electronic address: wenmoxiushi@163.com. 3. Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; Nanjing Institute of Supervision & Testing on Product Quality, Jiangsu, Nanjing 210028, PR China. 4. Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210046, PR China. 5. Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; Nanjing Institute of Supervision & Testing on Product Quality, Jiangsu, Nanjing 210028, PR China; College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210046, PR China. 6. Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China; Department of Pharmaceutics, Jiangsu University, Jiangsu, Zhenjiang 212013, PR China; College of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu, Nanjing 210046, PR China. Electronic address: jxiaobin2005@hotmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Moutan Cortex (MC, family: Paeonia suffruticosa Andr.) is a well-known traditional herbal medicine that has been shown to hold a protective effect on inflammation in several diseases. However, its anti-inflammatory activity on diabetic nephropathy (DN) has been less reported. The present study was conducted to evaluate the potential attenuation activities of MC on inflammation in AGEs-induced rat mesangial cells dysfunction and high-glucose-fat diet and streptozotocin (STZ)-induced DN rats and explore the possible mechanism underlying its DN effect. MATERIALS AND METHODS: The inflammation in mesangial cells (HBZY-1) was induced by 200 μg/ml advanced glycation end products (AGEs). DN rats model was established by an administration high-glucose-fat diet and an intraperitoneal injection of STZ (30 mg/kg). Interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) level in cell supernatant and rats serum were detected by appropriate kits. A co-culture system of mesangial cells and macrophages was performed to evaluate the migration of macrophages. Immunohistochemical assay was applied to examine transforming growth factor beta1 (TGF-β1), IL-6, MCP-1 and intercellular adhesion molecule-1 (ICAM-1) expression in kidney tissues of rats. Furthermore, western blot analysis was carried out to examine TGF-β1, IL-6, MCP-1, ICAM-1 and RAGE protein expressions in mesangial cells. RESULTS: Pretreatment with MC could significantly inhibit AGEs-induced migration of macrophages in the co-culture system of mesangial cell and macrophage. MC could decrease IL-6 and MCP-1 levels in serum of DN rats in a dose-dependent manner. Furthermore, MC also improved the blood glucose, serum creatinine and urine protein levels. Both immunocytochemistry analysis and western blot analysis showed that MC decreased significantly the over-expression of IL-6, MCP-1, TGF-β1, ICAM-1 and RAGE in mesangial cells or kidney tissues. Additionally, the protein expression of proinflammatory cytokine could also be down-regulated by the pretreatment of RAGE-Ab (5 μg/ml). CONCLUSION: These findings indicated that the extract of MC had an amelioration activity on the inflammation in AGEs-induced mesangial cells dysfunction and high-glucose-fat diet and STZ-induced DN rats. The protective effect might be associated with the intervention of MC via target of RAGE. These findings suggested that MC might be a benefit agent for the prevention and treatment of DN.
ETHNOPHARMACOLOGICAL RELEVANCE: Moutan Cortex (MC, family: Paeonia suffruticosa Andr.) is a well-known traditional herbal medicine that has been shown to hold a protective effect on inflammation in several diseases. However, its anti-inflammatory activity on diabetic nephropathy (DN) has been less reported. The present study was conducted to evaluate the potential attenuation activities of MC on inflammation in AGEs-induced rat mesangial cells dysfunction and high-glucose-fat diet and streptozotocin (STZ)-induced DN rats and explore the possible mechanism underlying its DN effect. MATERIALS AND METHODS: The inflammation in mesangial cells (HBZY-1) was induced by 200 μg/ml advanced glycation end products (AGEs). DN rats model was established by an administration high-glucose-fat diet and an intraperitoneal injection of STZ (30 mg/kg). Interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) level in cell supernatant and rats serum were detected by appropriate kits. A co-culture system of mesangial cells and macrophages was performed to evaluate the migration of macrophages. Immunohistochemical assay was applied to examine transforming growth factor beta1 (TGF-β1), IL-6, MCP-1 and intercellular adhesion molecule-1 (ICAM-1) expression in kidney tissues of rats. Furthermore, western blot analysis was carried out to examine TGF-β1, IL-6, MCP-1, ICAM-1 and RAGE protein expressions in mesangial cells. RESULTS: Pretreatment with MC could significantly inhibit AGEs-induced migration of macrophages in the co-culture system of mesangial cell and macrophage. MC could decrease IL-6 and MCP-1 levels in serum of DN rats in a dose-dependent manner. Furthermore, MC also improved the blood glucose, serum creatinine and urine protein levels. Both immunocytochemistry analysis and western blot analysis showed that MC decreased significantly the over-expression of IL-6, MCP-1, TGF-β1, ICAM-1 and RAGE in mesangial cells or kidney tissues. Additionally, the protein expression of proinflammatory cytokine could also be down-regulated by the pretreatment of RAGE-Ab (5 μg/ml). CONCLUSION: These findings indicated that the extract of MC had an amelioration activity on the inflammation in AGEs-induced mesangial cells dysfunction and high-glucose-fat diet and STZ-induced DN rats. The protective effect might be associated with the intervention of MC via target of RAGE. These findings suggested that MC might be a benefit agent for the prevention and treatment of DN.
Authors: Andréa E M Stinghen; Ziad A Massy; Helen Vlassara; Gary E Striker; Agnès Boullier Journal: J Am Soc Nephrol Date: 2015-08-26 Impact factor: 10.121
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