Limits...
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

Renal pathology and urinary albumin excretion from diabetic rats treated with Xiexin decoction. (a)–(f) Periodic acid-Schiff's reagent (PAS) stain. Original magnification (a)–(f) × 400. (g)–(r) Electron microscopy (EM) analysis. Representative images of glomerular basement membrane thickening (g)–(l) and mesangial matrix expansion (m)–(r), scale bars 2 μm, original magnification electron microscopy × 4,700. (s) Urinary albumin excretion at 4, 8, and 12 weeks. (t) Ratio of mesangial matrix area to glomerular area (M/G) in PAS staining. 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 intragastric gavage once a day for 12 weeks. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01 as compared with DM.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3713598&req=5

fig2: Renal pathology and urinary albumin excretion from diabetic rats treated with Xiexin decoction. (a)–(f) Periodic acid-Schiff's reagent (PAS) stain. Original magnification (a)–(f) × 400. (g)–(r) Electron microscopy (EM) analysis. Representative images of glomerular basement membrane thickening (g)–(l) and mesangial matrix expansion (m)–(r), scale bars 2 μm, original magnification electron microscopy × 4,700. (s) Urinary albumin excretion at 4, 8, and 12 weeks. (t) Ratio of mesangial matrix area to glomerular area (M/G) in PAS staining. 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 intragastric gavage once a day for 12 weeks. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01 as compared with DM.

Mentions: UAE was significantly increased at 4, 8, and 12 weeks, and creatinine clearance and the kidney weight to body weight ratio were also markedly increased at 12 weeks in the DM group, as compared with the NC group. In contrast, XXD and or losartan treatments significantly reduced UAE (Figure 2(s)), creatinine clearance, and kidney weight to body weight ratio, as compared with the DM group (Table 4). In addition, the diabetic rats treated with metformin for 12 weeks also exhibited a significant reduction in UAE (Figure 2(s)) and creatinine clearance (Table 4).


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)

Renal pathology and urinary albumin excretion from diabetic rats treated with Xiexin decoction. (a)–(f) Periodic acid-Schiff's reagent (PAS) stain. Original magnification (a)–(f) × 400. (g)–(r) Electron microscopy (EM) analysis. Representative images of glomerular basement membrane thickening (g)–(l) and mesangial matrix expansion (m)–(r), scale bars 2 μm, original magnification electron microscopy × 4,700. (s) Urinary albumin excretion at 4, 8, and 12 weeks. (t) Ratio of mesangial matrix area to glomerular area (M/G) in PAS staining. 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 intragastric gavage once a day for 12 weeks. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01 as compared with DM.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713598&req=5

fig2: Renal pathology and urinary albumin excretion from diabetic rats treated with Xiexin decoction. (a)–(f) Periodic acid-Schiff's reagent (PAS) stain. Original magnification (a)–(f) × 400. (g)–(r) Electron microscopy (EM) analysis. Representative images of glomerular basement membrane thickening (g)–(l) and mesangial matrix expansion (m)–(r), scale bars 2 μm, original magnification electron microscopy × 4,700. (s) Urinary albumin excretion at 4, 8, and 12 weeks. (t) Ratio of mesangial matrix area to glomerular area (M/G) in PAS staining. 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 intragastric gavage once a day for 12 weeks. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01 as compared with DM.
Mentions: UAE was significantly increased at 4, 8, and 12 weeks, and creatinine clearance and the kidney weight to body weight ratio were also markedly increased at 12 weeks in the DM group, as compared with the NC group. In contrast, XXD and or losartan treatments significantly reduced UAE (Figure 2(s)), creatinine clearance, and kidney weight to body weight ratio, as compared with the DM group (Table 4). In addition, the diabetic rats treated with metformin for 12 weeks also exhibited a significant reduction in UAE (Figure 2(s)) and creatinine clearance (Table 4).

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