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The anti-inflammatory and antifibrotic effects of Coreopsis tinctoria Nutt on high-glucose-fat diet and streptozotocin-induced diabetic renal damage in rats.

Yao L, Li L, Li X, Li H, Zhang Y, Zhang R, Wang J, Mao X - BMC Complement Altern Med (2015)

Bottom Line: Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis.However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1.AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Traditional Chinese Medicine, Xinjiang Medical University, Xinyi Street 393, Urumuqi, 830011, China. ylyl1026@sina.com.

ABSTRACT

Background: Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis. Coreopsis tinctoria Nutt, traditionally used as a healthcare tea, has anti-inflammatory, anti-hyperlipidemia, and glycemic regulation activities. The aim of our study was to investigate the renal protective effect of ethyl acetate extract of C. tinctoria Nutt (AC) on high-glucose-fat diet and streptozotocin (STZ)-induced diabetic rats.

Methods: A diabetic rat model was induced by high-glucose-fat diet and intraperitoneal injection of 35 mg/kg STZ. After treatment with AC at a daily dose of 150, 300 or, 600 mg/kg for 4 weeks, metabolic and renal function parameters of serum and urine were examined. Degree of renal damage, renal proinflammatory cytokines, and fibrotic protein expression were analyzed by histopathology and immunohistochemistry. Renal AMP-activated protein kinase (AMPK) and transforming growth factor (TGF)-β1/Smad signaling pathway were determined by western blotting.

Results: Diabetic rats showed obvious renal dysfunction, inflammation and fibrosis. However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1. AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway. Meanwhile, AMPKα as a protective cytokine was markedly stimulated by AC.

Conclusion: In summary, AC controls blood glucose, inhibits inflammatory and fibrotic processes, suppresses the TGF-β1/Smad signaling pathway, and activates phosphorylation of AMPKα in the kidneys, which confirms the protective effects of AC in the early stage of diabetic kidney disease.

No MeSH data available.


Related in: MedlinePlus

Effect of AC on protein expression of TGF-β1, Smad2 and p-Smad2. a TGF-β1, Smad2 and p-Smad2 expression in right kidney. b Band density analysis of TGF-β1, Smad2 and p-Smad2. Values were expressed as mean ± SEM (n = 4). #P < 0.01 versus normal group; *P < 0.05 versus control group; **P < 0.01 versus control group
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Fig5: Effect of AC on protein expression of TGF-β1, Smad2 and p-Smad2. a TGF-β1, Smad2 and p-Smad2 expression in right kidney. b Band density analysis of TGF-β1, Smad2 and p-Smad2. Values were expressed as mean ± SEM (n = 4). #P < 0.01 versus normal group; *P < 0.05 versus control group; **P < 0.01 versus control group

Mentions: To elucidate the mechanism of the anti-inflammatory and antifibrotic effects of AC, the TGF-β1/Smad and AMPK signaling pathways were investigated by western blotting. The TGF-β1/Smad signaling pathway was considered to play a vital role in progression of renal fibrosis. As shown in Fig. 5a, b, TGF-β1 expression in diabetic rats was significantly increased, followed by overexpression of phospho (p)-Smad2. Whereas, TGF-β1 and p-Smad2 expression was markedly decreased by treatment with AC. The active form of AMPKα was more highly expressed in normal rats than diabetic rats (P < 0.01). Treatment with AC (150, 300 and 600 mg/kg) and metformin significantly upregulated the p-AMPKα expression (Fig. 6a, b). These results indicated that the anti-inflammatory and antifibrotic effects of AC were possibly related to TGF-β1/Smad and AMPK signaling pathways.Fig. 5


The anti-inflammatory and antifibrotic effects of Coreopsis tinctoria Nutt on high-glucose-fat diet and streptozotocin-induced diabetic renal damage in rats.

Yao L, Li L, Li X, Li H, Zhang Y, Zhang R, Wang J, Mao X - BMC Complement Altern Med (2015)

Effect of AC on protein expression of TGF-β1, Smad2 and p-Smad2. a TGF-β1, Smad2 and p-Smad2 expression in right kidney. b Band density analysis of TGF-β1, Smad2 and p-Smad2. Values were expressed as mean ± SEM (n = 4). #P < 0.01 versus normal group; *P < 0.05 versus control group; **P < 0.01 versus control group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4561427&req=5

Fig5: Effect of AC on protein expression of TGF-β1, Smad2 and p-Smad2. a TGF-β1, Smad2 and p-Smad2 expression in right kidney. b Band density analysis of TGF-β1, Smad2 and p-Smad2. Values were expressed as mean ± SEM (n = 4). #P < 0.01 versus normal group; *P < 0.05 versus control group; **P < 0.01 versus control group
Mentions: To elucidate the mechanism of the anti-inflammatory and antifibrotic effects of AC, the TGF-β1/Smad and AMPK signaling pathways were investigated by western blotting. The TGF-β1/Smad signaling pathway was considered to play a vital role in progression of renal fibrosis. As shown in Fig. 5a, b, TGF-β1 expression in diabetic rats was significantly increased, followed by overexpression of phospho (p)-Smad2. Whereas, TGF-β1 and p-Smad2 expression was markedly decreased by treatment with AC. The active form of AMPKα was more highly expressed in normal rats than diabetic rats (P < 0.01). Treatment with AC (150, 300 and 600 mg/kg) and metformin significantly upregulated the p-AMPKα expression (Fig. 6a, b). These results indicated that the anti-inflammatory and antifibrotic effects of AC were possibly related to TGF-β1/Smad and AMPK signaling pathways.Fig. 5

Bottom Line: Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis.However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1.AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Traditional Chinese Medicine, Xinjiang Medical University, Xinyi Street 393, Urumuqi, 830011, China. ylyl1026@sina.com.

ABSTRACT

Background: Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis. Coreopsis tinctoria Nutt, traditionally used as a healthcare tea, has anti-inflammatory, anti-hyperlipidemia, and glycemic regulation activities. The aim of our study was to investigate the renal protective effect of ethyl acetate extract of C. tinctoria Nutt (AC) on high-glucose-fat diet and streptozotocin (STZ)-induced diabetic rats.

Methods: A diabetic rat model was induced by high-glucose-fat diet and intraperitoneal injection of 35 mg/kg STZ. After treatment with AC at a daily dose of 150, 300 or, 600 mg/kg for 4 weeks, metabolic and renal function parameters of serum and urine were examined. Degree of renal damage, renal proinflammatory cytokines, and fibrotic protein expression were analyzed by histopathology and immunohistochemistry. Renal AMP-activated protein kinase (AMPK) and transforming growth factor (TGF)-β1/Smad signaling pathway were determined by western blotting.

Results: Diabetic rats showed obvious renal dysfunction, inflammation and fibrosis. However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1. AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway. Meanwhile, AMPKα as a protective cytokine was markedly stimulated by AC.

Conclusion: In summary, AC controls blood glucose, inhibits inflammatory and fibrotic processes, suppresses the TGF-β1/Smad signaling pathway, and activates phosphorylation of AMPKα in the kidneys, which confirms the protective effects of AC in the early stage of diabetic kidney disease.

No MeSH data available.


Related in: MedlinePlus