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Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

Lim SW, Doh KC, Jin L, Piao SG, Heo SB, Zheng YF, Bae SK, Chung BH, Yang CW - PLoS ONE (2013)

Bottom Line: Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line.Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death.The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul, Korea.

ABSTRACT

Background: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury.

Methods: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media.

Results: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine.

Conclusions: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

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Effect of KRG on pancreatic function in CsA-induced pancreatic injury.(A and B) Results of IPGTT among the experimental groups. CsA-treated mice had significantly elevated blood glucose compared with the VH-only control group at 30 and 60 min. CsA plus daily treatment with 0.2 or 0.4 mg/kg KRG (K0.2 or K0.4, respectively) decreased blood glucose levels significantly at 30 and 60 min compared with the CsA-only group. (C) Calculation of the AUCg for the experimental groups. CsA plus K0.2 or K0.4 treatment resulted in a decreased AUCg compared with the CsA-only group. (D) Serum insulin levels in the experimental groups. The CsA plus K0.2 or K0.4 groups had significantly increased insulin levels compared with the CsA-only group. Values are mean ± standard errors (SE: n = 10). #P<0.05 vs. VH; *P<0.05 vs. CsA; †P<0.05 vs. CsA+K0.2; ‡P<0.05 vs. CsA+K0.4.
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pone-0072685-g001: Effect of KRG on pancreatic function in CsA-induced pancreatic injury.(A and B) Results of IPGTT among the experimental groups. CsA-treated mice had significantly elevated blood glucose compared with the VH-only control group at 30 and 60 min. CsA plus daily treatment with 0.2 or 0.4 mg/kg KRG (K0.2 or K0.4, respectively) decreased blood glucose levels significantly at 30 and 60 min compared with the CsA-only group. (C) Calculation of the AUCg for the experimental groups. CsA plus K0.2 or K0.4 treatment resulted in a decreased AUCg compared with the CsA-only group. (D) Serum insulin levels in the experimental groups. The CsA plus K0.2 or K0.4 groups had significantly increased insulin levels compared with the CsA-only group. Values are mean ± standard errors (SE: n = 10). #P<0.05 vs. VH; *P<0.05 vs. CsA; †P<0.05 vs. CsA+K0.2; ‡P<0.05 vs. CsA+K0.4.

Mentions: Table 1 shows the effects of 4 weeks of CsA and KRG (K) treatment on the basic parameters of the experimental groups. Both CsA+K groups (one treated daily with 0.2 g/kg and one with 0.4 g/kg of KRG) showed lower serum creatinine (Scr) and blood urea nitrogen (BUN) than the CsA only group. KRG cotreatment did not affect the CsA level in either whole blood or pancreatic tissues, indicating that drug interactions did not occur at these doses. Baseline blood glucose levels did not differ among the four groups (Figure 1A and B). However, the blood glucose level after intraperitoneal glucose loading was significantly higher in the CsA group than in the VH group, but cotreatment with KRG significantly decreased the blood glucose level at 30 and 60 min after glucose loading compared with the CsA group. KRG cotreatment with CsA decreased the calculated area under the curve for glucose (AUCg) compared with the CsA group (Figure 1C: VH, 1229±55 mg/dL/min; VH+K0.2, 1174±49 mg/dL/min; VH+K0.4, 1360±35 mg/dL/min; CsA, 1563±39 mg/dL/min; CsA+K0.2, 1447±32 mg/dL/min; CsA+K0.4, 1368±44 mg/dL/min; VH vs. CsA, CsA vs. CsA+K0.2 or CsA+K0.4, P<0.05). The fasting insulin level was significantly lower in the CsA group than in the VH group. It was significantly increased in both CsA+K groups compared with the CsA group (Figure 1D: VH, 0.30±0.05 ng/mL; VH+K0.2, 0.33±0.05 ng/mL; VH+K0.4, 0.30±0.04 ng/mL; CsA, 0.15±0.01 ng/mL; CsA+K0.2, 0.19±0.01 ng/mL; CsA+K0.4, 0.30±0.06 ng/mL; VH vs. CsA, CsA vs. CsA+K0.2 or CsA+K0.4, P<0.05). Thus, oral KRG administration during CsA-induced pancreatic dysfunction in mice improved glucose tolerance and restored defective insulin secretion, suggesting that KRG has an antihyperglycemic effect.


Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

Lim SW, Doh KC, Jin L, Piao SG, Heo SB, Zheng YF, Bae SK, Chung BH, Yang CW - PLoS ONE (2013)

Effect of KRG on pancreatic function in CsA-induced pancreatic injury.(A and B) Results of IPGTT among the experimental groups. CsA-treated mice had significantly elevated blood glucose compared with the VH-only control group at 30 and 60 min. CsA plus daily treatment with 0.2 or 0.4 mg/kg KRG (K0.2 or K0.4, respectively) decreased blood glucose levels significantly at 30 and 60 min compared with the CsA-only group. (C) Calculation of the AUCg for the experimental groups. CsA plus K0.2 or K0.4 treatment resulted in a decreased AUCg compared with the CsA-only group. (D) Serum insulin levels in the experimental groups. The CsA plus K0.2 or K0.4 groups had significantly increased insulin levels compared with the CsA-only group. Values are mean ± standard errors (SE: n = 10). #P<0.05 vs. VH; *P<0.05 vs. CsA; †P<0.05 vs. CsA+K0.2; ‡P<0.05 vs. CsA+K0.4.
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pone-0072685-g001: Effect of KRG on pancreatic function in CsA-induced pancreatic injury.(A and B) Results of IPGTT among the experimental groups. CsA-treated mice had significantly elevated blood glucose compared with the VH-only control group at 30 and 60 min. CsA plus daily treatment with 0.2 or 0.4 mg/kg KRG (K0.2 or K0.4, respectively) decreased blood glucose levels significantly at 30 and 60 min compared with the CsA-only group. (C) Calculation of the AUCg for the experimental groups. CsA plus K0.2 or K0.4 treatment resulted in a decreased AUCg compared with the CsA-only group. (D) Serum insulin levels in the experimental groups. The CsA plus K0.2 or K0.4 groups had significantly increased insulin levels compared with the CsA-only group. Values are mean ± standard errors (SE: n = 10). #P<0.05 vs. VH; *P<0.05 vs. CsA; †P<0.05 vs. CsA+K0.2; ‡P<0.05 vs. CsA+K0.4.
Mentions: Table 1 shows the effects of 4 weeks of CsA and KRG (K) treatment on the basic parameters of the experimental groups. Both CsA+K groups (one treated daily with 0.2 g/kg and one with 0.4 g/kg of KRG) showed lower serum creatinine (Scr) and blood urea nitrogen (BUN) than the CsA only group. KRG cotreatment did not affect the CsA level in either whole blood or pancreatic tissues, indicating that drug interactions did not occur at these doses. Baseline blood glucose levels did not differ among the four groups (Figure 1A and B). However, the blood glucose level after intraperitoneal glucose loading was significantly higher in the CsA group than in the VH group, but cotreatment with KRG significantly decreased the blood glucose level at 30 and 60 min after glucose loading compared with the CsA group. KRG cotreatment with CsA decreased the calculated area under the curve for glucose (AUCg) compared with the CsA group (Figure 1C: VH, 1229±55 mg/dL/min; VH+K0.2, 1174±49 mg/dL/min; VH+K0.4, 1360±35 mg/dL/min; CsA, 1563±39 mg/dL/min; CsA+K0.2, 1447±32 mg/dL/min; CsA+K0.4, 1368±44 mg/dL/min; VH vs. CsA, CsA vs. CsA+K0.2 or CsA+K0.4, P<0.05). The fasting insulin level was significantly lower in the CsA group than in the VH group. It was significantly increased in both CsA+K groups compared with the CsA group (Figure 1D: VH, 0.30±0.05 ng/mL; VH+K0.2, 0.33±0.05 ng/mL; VH+K0.4, 0.30±0.04 ng/mL; CsA, 0.15±0.01 ng/mL; CsA+K0.2, 0.19±0.01 ng/mL; CsA+K0.4, 0.30±0.06 ng/mL; VH vs. CsA, CsA vs. CsA+K0.2 or CsA+K0.4, P<0.05). Thus, oral KRG administration during CsA-induced pancreatic dysfunction in mice improved glucose tolerance and restored defective insulin secretion, suggesting that KRG has an antihyperglycemic effect.

Bottom Line: Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line.Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death.The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul, Korea.

ABSTRACT

Background: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury.

Methods: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media.

Results: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine.

Conclusions: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

Show MeSH
Related in: MedlinePlus