Bin Zhang1,2,3,4, Xuelian Zhang1,2,3,4, Chenyang Zhang1,2,3,4, Guibo Sun5,6,7,8, Xiaobo Sun9,10,11,12. 1. Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China. 2. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China. 3. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, 100193, China. 4. Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, 100193, China. 5. Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China. sunguibo@126.com. 6. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China. sunguibo@126.com. 7. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, 100193, China. sunguibo@126.com. 8. Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, 100193, China. sunguibo@126.com. 9. Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China. sun-xiaobo@163.com. 10. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China. sun-xiaobo@163.com. 11. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, 100193, China. sun-xiaobo@163.com. 12. Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing, 100193, China. sun-xiaobo@163.com.
Abstract
PURPOSE: Diabetic nephropathy (DN), one of severe diabetic complications in the diabetes, is the main cause of end stage renal disease (ESRD). Notably, the currently available medications used to treat DN remain limited. Here, we determined whether berberine (BBR) could enhance the anti-diabetic nephropathy activities of metformin (Met) and explored its possible mechanisms. METHOD: The anti-diabetic nephropathy properties were systematically analyzed in the diabetic db/db mice treated with Met, BBR or with combination of Met and BBR. RESULTS: We found that both single Met and BBR treatments, and combination therapy could lower blood glucose, and ameliorate insulin resistance. The improvement of lipids metabolism by co-administration was more evident, as indicated by reduced serum cholesterol and less fat accumulation in the liver. Further, it was found that Met and BBR treatments, and co-administration could attenuate the progression of DN. However, anti-diabetic nephropathy activities of Met were enhanced when combined with BBR, as evidenced by improved renal function and histological abnormalities of diabetic kidney. Mechanistically, BBR enhanced renal-protective effects of Met primarily through potently promoting expression of Trib1, which subsequently downregulated the increased protein levels of CCAAT/enhancer binding protein α (C/EBPα), and eventually inhibited fatty synthesis proteins and nuclear factor kappa-B (NF-κB) signaling. CONCLUSION: Our data provide novel insight that co-administration of BBR and Met exerts a preferable activity of anti-diabetic nephropathy via collectively enhancing lipolysis and inhibiting inflammation. Combination therapy with these two drugs may provide an effective therapeutic strategy for the medical treatment of diabetic nephropathy.
PURPOSE: Diabetic nephropathy (DN), one of severe diabetic complications in the diabetes, is the main cause of end stage renal disease (ESRD). Notably, the currently available medications used to treat DN remain limited. Here, we determined whether berberine (BBR) could enhance the anti-diabetic nephropathy activities of metformin (Met) and explored its possible mechanisms. METHOD: The anti-diabetic nephropathy properties were systematically analyzed in the diabetic db/db mice treated with Met, BBR or with combination of Met and BBR. RESULTS: We found that both single Met and BBR treatments, and combination therapy could lower blood glucose, and ameliorate insulin resistance. The improvement of lipids metabolism by co-administration was more evident, as indicated by reduced serum cholesterol and less fat accumulation in the liver. Further, it was found that Met and BBR treatments, and co-administration could attenuate the progression of DN. However, anti-diabetic nephropathy activities of Met were enhanced when combined with BBR, as evidenced by improved renal function and histological abnormalities of diabetic kidney. Mechanistically, BBR enhanced renal-protective effects of Met primarily through potently promoting expression of Trib1, which subsequently downregulated the increased protein levels of CCAAT/enhancer binding protein α (C/EBPα), and eventually inhibited fatty synthesis proteins and nuclear factor kappa-B (NF-κB) signaling. CONCLUSION: Our data provide novel insight that co-administration of BBR and Met exerts a preferable activity of anti-diabetic nephropathy via collectively enhancing lipolysis and inhibiting inflammation. Combination therapy with these two drugs may provide an effective therapeutic strategy for the medical treatment of diabetic nephropathy.
Authors: Camille A Jones; Andrzej S Krolewski; John Rogus; Jay L Xue; Allan Collins; James H Warram Journal: Kidney Int Date: 2005-05 Impact factor: 10.612
Authors: Thijs W Cohen Tervaert; Antien L Mooyaart; Kerstin Amann; Arthur H Cohen; H Terence Cook; Cinthia B Drachenberg; Franco Ferrario; Agnes B Fogo; Mark Haas; Emile de Heer; Kensuke Joh; Laure H Noël; Jai Radhakrishnan; Surya V Seshan; Ingeborg M Bajema; Jan A Bruijn Journal: J Am Soc Nephrol Date: 2010-02-18 Impact factor: 10.121
Authors: Wai Han Yiu; Rui Xi Li; Dickson W L Wong; Hao Jia Wu; Kam Wa Chan; Loretta Y Y Chan; Joseph C K Leung; Kar Neng Lai; Steven H Sacks; Wuding Zhou; Sydney C W Tang Journal: Nephrol Dial Transplant Date: 2018-08-01 Impact factor: 5.992