Jia-Sheng Wu1, Yuan Liu2, Rong Shi1, Xiong Lu3, Yue-Ming Ma4, Neng-Neng Cheng5. 1. Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. 3. Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 4. Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: mayueming_117@hotmail.com. 5. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. Electronic address: nncheng@gmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Xiexin decoction (XXD) has been used as a treatment for diabetes mellitus for more than 1300 years. XXD constituents with protective effects against diabetic nephropathy (DN) include Rhizoma Coptidis alkaloids (RA), Radix et Rhizoma Rhei polysaccharides (RP), and Radix Scutellaria flavones (RF). The aim of the study is to investigate the effects of combinations of RA, RP, and RF on DN and their mechanisms of action. MATERIALS AND METHODS: In vitro, high glucose-induced rat mesangial cells were treated with RA, RP, RF, and combinations thereof. Cell proliferation and levels of inflammatory factors were measured. In vivo, high-fat diet and streptozotocin-induced diabetic rats were treated with different combinations of RA, RP, and RF once per day for 12 weeks. Blood and urine biochemical parameters, renal tissue morphology, and inflammation were investigated. RESULTS: In vitro, the combination of the three groups of components inhibited mesangial cell proliferation and reduced the levels of monocyte chemotactic protein-1 (MCP-1) and collagen IV. The effects of the three constituent groups in combination were stronger than those of each group alone or combinations of two groups. In diabetic rats, combinations of the three groups of herb components ameliorated blood glucose, urinary albumin excretion and decreased renal mesangial matrix expansion and basement membrane thickening. In addition, the combinations reduced renal tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) protein levels, down-regulated the expression of nuclear factor κB (NF-κB) and transforming growth factor beta 1 (TGF-β1), and up-regulated the expression of inhibitor of nuclear factor κB (IκB) protein. Among the three groups of herb components, RA produced the strongest effects, followed by RP, and then by RF. CONCLUSIONS: The combination of the three groups of herb components produced anti-DN effects through inhibition of inflammation mediated by NF-κB. Among the three groups of herb components, RA produced the strongest effect while RP and RF produced weaker effects.
ETHNOPHARMACOLOGICAL RELEVANCE: Xiexin decoction (XXD) has been used as a treatment for diabetes mellitus for more than 1300 years. XXD constituents with protective effects against diabetic nephropathy (DN) include Rhizoma Coptidis alkaloids (RA), Radix et Rhizoma Rhei polysaccharides (RP), and Radix Scutellaria flavones (RF). The aim of the study is to investigate the effects of combinations of RA, RP, and RF on DN and their mechanisms of action. MATERIALS AND METHODS: In vitro, high glucose-induced rat mesangial cells were treated with RA, RP, RF, and combinations thereof. Cell proliferation and levels of inflammatory factors were measured. In vivo, high-fat diet and streptozotocin-induced diabeticrats were treated with different combinations of RA, RP, and RF once per day for 12 weeks. Blood and urine biochemical parameters, renal tissue morphology, and inflammation were investigated. RESULTS: In vitro, the combination of the three groups of components inhibited mesangial cell proliferation and reduced the levels of monocyte chemotactic protein-1 (MCP-1) and collagen IV. The effects of the three constituent groups in combination were stronger than those of each group alone or combinations of two groups. In diabeticrats, combinations of the three groups of herb components ameliorated blood glucose, urinary albumin excretion and decreased renal mesangial matrix expansion and basement membrane thickening. In addition, the combinations reduced renal tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) protein levels, down-regulated the expression of nuclear factor κB (NF-κB) and transforming growth factor beta 1 (TGF-β1), and up-regulated the expression of inhibitor of nuclear factor κB (IκB) protein. Among the three groups of herb components, RA produced the strongest effects, followed by RP, and then by RF. CONCLUSIONS: The combination of the three groups of herb components produced anti-DN effects through inhibition of inflammation mediated by NF-κB. Among the three groups of herb components, RA produced the strongest effect while RP and RF produced weaker effects.