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Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats.

Wu JS, Shi R, Zhong J, Lu X, Ma BL, Wang TM, Zan B, Ma YM, Cheng NN, Qiu FR - Evid Based Complement Alternat Med (2013)

Bottom Line: XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor- κ B pathway activity, and downregulated renal transforming growth factor- β 1.Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets.Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor- κ B pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
In Chinese medicine, Xiexin decoction (XXD) has been used for the clinical treatment of diabetes for at least 1700 years. The present study was conducted to investigate the effective ingredients of XXD and their molecular mechanisms of antidiabetic nephropathy in rats. Rats with diabetes induced by high-fat diet and streptozotocin were treated with XXD extract for 12 weeks. XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor- κ B pathway activity, and downregulated renal transforming growth factor- β 1. The concentrations of multiple components in plasma from XXD were determined by liquid chromatography and tandem mass spectrometry. Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets. Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor- κ B pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats.

No MeSH data available.


Related in: MedlinePlus

Effects of Xiexin decoction on renal inflammation factor and transforming growth factor β1 (TGF-β1) expression in diabetic rats. (a)–(c) Western blot analysis of protein levels; (d)–(f) Real-time PCR analysis of mRNA levels; (g)–(h) Quantification by ELISA. NC: normal control; DM: diabetic model control; XXDL: XXD extract 1.25 g/kg; XXDH: XXD extract 2.5 g/kg; losartan 10 mg/kg and metformin 100 mg/kg. NC and DM were treated with normal saline. All the rats were administered via intragastric gavage once time each day for 12 weeks. ICAM-1: intercellular adhesion molecule-1; MCP-1: monocyte chemotactic protein-1; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6. Data are expressed as mean ± SD *P < 0.05, **P < 0.01 as compared with DM.
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fig4: Effects of Xiexin decoction on renal inflammation factor and transforming growth factor β1 (TGF-β1) expression in diabetic rats. (a)–(c) Western blot analysis of protein levels; (d)–(f) Real-time PCR analysis of mRNA levels; (g)–(h) Quantification by ELISA. NC: normal control; DM: diabetic model control; XXDL: XXD extract 1.25 g/kg; XXDH: XXD extract 2.5 g/kg; losartan 10 mg/kg and metformin 100 mg/kg. NC and DM were treated with normal saline. All the rats were administered via intragastric gavage once time each day for 12 weeks. ICAM-1: intercellular adhesion molecule-1; MCP-1: monocyte chemotactic protein-1; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6. Data are expressed as mean ± SD *P < 0.05, **P < 0.01 as compared with DM.

Mentions: After 12 weeks of diabetes, renal protein and mRNA MCP-1 and ICAM-1 expression, and levels of TNF-α and IL-6, were markedly increased in the DM group, as compared with NC rats. Renal TGF-β1 protein and mRNA expression were also significantly increased in DM. XXD and losartan treatment significantly downregulated these changes (Figure 4). In addition, the diabetic rats treated with metformin also exhibited a significant reduction in MCP-1 and ICAM-1 expression and TNF-α level (Figure 4). Collectively, these data indicated that XXD could suppress the renal inflammation induced by diabetes.


Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats.

Wu JS, Shi R, Zhong J, Lu X, Ma BL, Wang TM, Zan B, Ma YM, Cheng NN, Qiu FR - Evid Based Complement Alternat Med (2013)

Effects of Xiexin decoction on renal inflammation factor and transforming growth factor β1 (TGF-β1) expression in diabetic rats. (a)–(c) Western blot analysis of protein levels; (d)–(f) Real-time PCR analysis of mRNA levels; (g)–(h) Quantification by ELISA. NC: normal control; DM: diabetic model control; XXDL: XXD extract 1.25 g/kg; XXDH: XXD extract 2.5 g/kg; losartan 10 mg/kg and metformin 100 mg/kg. NC and DM were treated with normal saline. All the rats were administered via intragastric gavage once time each day for 12 weeks. ICAM-1: intercellular adhesion molecule-1; MCP-1: monocyte chemotactic protein-1; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6. Data are expressed as mean ± SD *P < 0.05, **P < 0.01 as compared with DM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: Effects of Xiexin decoction on renal inflammation factor and transforming growth factor β1 (TGF-β1) expression in diabetic rats. (a)–(c) Western blot analysis of protein levels; (d)–(f) Real-time PCR analysis of mRNA levels; (g)–(h) Quantification by ELISA. NC: normal control; DM: diabetic model control; XXDL: XXD extract 1.25 g/kg; XXDH: XXD extract 2.5 g/kg; losartan 10 mg/kg and metformin 100 mg/kg. NC and DM were treated with normal saline. All the rats were administered via intragastric gavage once time each day for 12 weeks. ICAM-1: intercellular adhesion molecule-1; MCP-1: monocyte chemotactic protein-1; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6. Data are expressed as mean ± SD *P < 0.05, **P < 0.01 as compared with DM.
Mentions: After 12 weeks of diabetes, renal protein and mRNA MCP-1 and ICAM-1 expression, and levels of TNF-α and IL-6, were markedly increased in the DM group, as compared with NC rats. Renal TGF-β1 protein and mRNA expression were also significantly increased in DM. XXD and losartan treatment significantly downregulated these changes (Figure 4). In addition, the diabetic rats treated with metformin also exhibited a significant reduction in MCP-1 and ICAM-1 expression and TNF-α level (Figure 4). Collectively, these data indicated that XXD could suppress the renal inflammation induced by diabetes.

Bottom Line: XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor- κ B pathway activity, and downregulated renal transforming growth factor- β 1.Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets.Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor- κ B pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
In Chinese medicine, Xiexin decoction (XXD) has been used for the clinical treatment of diabetes for at least 1700 years. The present study was conducted to investigate the effective ingredients of XXD and their molecular mechanisms of antidiabetic nephropathy in rats. Rats with diabetes induced by high-fat diet and streptozotocin were treated with XXD extract for 12 weeks. XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor- κ B pathway activity, and downregulated renal transforming growth factor- β 1. The concentrations of multiple components in plasma from XXD were determined by liquid chromatography and tandem mass spectrometry. Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets. Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor- κ B pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats.

No MeSH data available.


Related in: MedlinePlus