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Kang, Kim, Kim, Seo, Han, Chun, Hur, Ahn, Ha, Jung, Cha, and Lee: Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan
Original Article
Korean Diabetes Journal

Korean Diabetes Journal 2008; 32(1): 10-20.

Published online: 29 February 2008

DOI: https://doi.org/10.4093/kdj.2008.32.1.10

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan

Eun Seok Kang1, 2, 3, Beom Seok Kim4, Chul Hoon Kim2, 5, Gi Ho Seo2, 5, Seung Jin Han1, Sung Wan Chun1, Kyu Yeon Hur1, Chul Woo Ahn1, 2, 3, Hunjoo Ha6, Mankil Jung7, Bong Soo Cha1, 2, 3, Hyun Chul Lee1, 2, 3

Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine1, Korea.

Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine2, Korea.

Institute of Endocrine Research, Yonsei University College of Medicine3, Korea.

Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine4, Korea.

Department of Pharmacology, Yonsei University College of Medicine5, Korea.

Ewha Womans University College of Pharmacy and Center for Cell Signaling and Drug Discovery Research6, Korea.

Department of Chemistry, Yonsei University College of Science7, Korea.

Received 28 November 2007       Accepted 14 January 2008

Copyright © 2008 Korean Diabetes Association

Abstract

Background

Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.

Methods

LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks.

Results

None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1).

Conclusion

These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

Keywords: Lithospermic acid B, Amlodipine, Losartan, OLETF rats, Diabetic nephropathy

Figures and Tables

Fig. 1
Body weight change over time. Treatment with LAB (n = 6), losartan (n = 6), or amlodipine had no effect on the body weight gain compared with PBS treated OLETF control rats (n = 6). *P < 0.05 compared with LETO (n = 6).
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Fig. 2
Profiles of systolic blood pressure change. OLETF rats progressively developed hypertension, whereas treatment with either losartan (n = 6), amlodipine (n = 6), or LAB (n = 6) reduced systolic blood pressure significantly. Treatment with losartan and amlodipine resulted in similar reductions in SBP, while treatment with LAB had a less potent effect on lowering blood pressure. *P < 0.05 compared with LETO (n = 6), †P < 0.05 compared with PBS treated OLETF (n = 6). a and b represent P < 0.05.
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Fig. 3
A. Renin mRNA expression profile. B. Angiotensinogen mRNA expression profile. At 38 weeks of age, OLETF rat showed higher renal renin and angiotensinogen mRNA levels than LETO rats. Treatment with losartan (n = 6) significantly increased renin mRNA levels but had no effect on angiotensinogen mRNA levels in OLETF rats. Treatment with amlodipine (n = 6) or LAB (n = 6) had no significant effects on renin and angiotensinogen mRNA expression level in OLETF rats. Values are means ± SE. *P < 0.05 compared with LETO (n = 6), †P < 0.05 compared with PBS treated OLETF (n = 6).
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Fig. 4
Profile of renal MCP-1 levels by relative PCR. MCP-1 level in creased in OLETF rats compared with LETO rats. Only treatment with LAB caused a decrease in renal cortical MCP-1 mRNA expression levels. LAB decreased amount of MCP-1 expression to the 57% level of PBS treated OLETF control (n = 6).
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Fig. 5
Profiles of glucose tolerance test at 38 weeks. Blood glucose levels were the greatest 30 min after the intraperitoneal glucose injection in all animals, which was followed by a distinct disposal phase. There was a delay in blood glucose disposal in OLETF rats. Treatment with LAB (n = 6), losartan (n = 6), or amlodipine (n = 6) did not significantly influence fasting and postprandial plasma glucose levels. *P < 0.05 compared with LETO (n = 6).
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Fig. 6
Effects on albuminuria. The amount of albuminuria was markedly suppressed by treatment with losartan (n = 6) and LAB (n = 6), but not with amlodipine (n = 6). Values are means ± SE. *P < 0.05 compared with LETO (n = 6), †P < 0.05 compared with OLETF (n = 6).
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Fig. 7
ELISA results for TGF-β1 protein expression in the kidney cortex. Quantitative analyses of TGF-β1 showed that losartan (n = 6) and LAB (n = 6) strongly inhibited TGF-β1 protein expression in the renal cortex of OLETF rats. Values are means ± SE. *P < 0.05 compared with LETO (n = 6), †P < 0.05 compared with PBS treated OLETF (n = 6).
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Fig. 8
Effect of treatments on renal cortex MDA levels. OLETF rats showed higher levels of renal cortical MDA contents compared with LETO rats. Treatment with amlodipine (n = 6), losartan (n = 6) or LAB (n = 6) decreased the renal cortical MDA concentration. Values are means ± SE. *P < 0.05 compared with LETO (n = 6), †P < 0.05 compared with PBS treated OLETF (n = 6). a and b represent P < 0.05.
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Table 1
Characteristics of experimental groups at 38 weeks
kdj-32-10-i001

Values are means ± SE. AST, Aspartate aminotransferase; ALT, Alanine aminotransferase. *P < 0.05 compared to LETO; †P < 0.05 compared to OLETF.

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