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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 apoptotic cell death in INS-1 cells during CsA-induced injury.(A and B) TUNEL staining was used to detect apoptosis, and its quantitative analysis is shown for INS-1 cells treated with either CsA alone or CsA plus 1 or 10 µg/mL of KRG for 24 h. TUNEL-positive nuclei (arrows) were rarely observed in the control group or in those treated with KRG alone. However, the numbers of TUNEL-positive nuclei increased significantly with CsA treatment compared with the control, and the addition of KRG decreased this. (C) Immunoblot analyses for Bcl-2, Bax and active caspase-3 in the INS-1 cells. The expression of Bcl-2 was reduced significantly in both CsA plus K groups compared with the CsA-alone group. By contrast, the expression levels of Bax and active caspase-3 were reduced in both CsA plus K groups compared with the CsA-only group. Magnifications×400. Relative optical densities of bands in each lane were normalized with each β-actin band from the same gel. #P<0.05 vs. Control or K1 or K10; *P<0.05 vs. CsA.
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pone-0072685-g007: Effect of KRG on apoptotic cell death in INS-1 cells during CsA-induced injury.(A and B) TUNEL staining was used to detect apoptosis, and its quantitative analysis is shown for INS-1 cells treated with either CsA alone or CsA plus 1 or 10 µg/mL of KRG for 24 h. TUNEL-positive nuclei (arrows) were rarely observed in the control group or in those treated with KRG alone. However, the numbers of TUNEL-positive nuclei increased significantly with CsA treatment compared with the control, and the addition of KRG decreased this. (C) Immunoblot analyses for Bcl-2, Bax and active caspase-3 in the INS-1 cells. The expression of Bcl-2 was reduced significantly in both CsA plus K groups compared with the CsA-alone group. By contrast, the expression levels of Bax and active caspase-3 were reduced in both CsA plus K groups compared with the CsA-only group. Magnifications×400. Relative optical densities of bands in each lane were normalized with each β-actin band from the same gel. #P<0.05 vs. Control or K1 or K10; *P<0.05 vs. CsA.

Mentions: To investigate the underlying molecular mechanisms of the antiapoptotic effect of KRG in CsA-induced injury, INS-1 cells were treated with CsA alone or combined with KRG (1 or 10 µg/mL) for 24 h. Figures 7A and 7B show TUNEL staining and its quantitative analysis in the four groups. The number of TUNEL-positive cells increased significantly with CsA treatment compared with the control, but the addition of KRG decreased them (Control, 1.1±0.3; K10, 0.9±0.2; CsA, 35.7±5.2; CsA+K10, 18.2±2.3; CsA vs. control or K10; CsA vs. CsA+K10, P<0.05). Figure 7C shows that CsA suppressed expression of the antiapoptotic marker Bcl-2 but that this suppression was attenuated by cotreatment with KRG. CsA treatment induced the expression levels of the proapoptotic markers Bax and active caspase-3, and these were attenuated by cotreatment with KRG. Thus, KRG had antiapoptotic effects in INS-1 cells during CsA treatment.


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 apoptotic cell death in INS-1 cells during CsA-induced injury.(A and B) TUNEL staining was used to detect apoptosis, and its quantitative analysis is shown for INS-1 cells treated with either CsA alone or CsA plus 1 or 10 µg/mL of KRG for 24 h. TUNEL-positive nuclei (arrows) were rarely observed in the control group or in those treated with KRG alone. However, the numbers of TUNEL-positive nuclei increased significantly with CsA treatment compared with the control, and the addition of KRG decreased this. (C) Immunoblot analyses for Bcl-2, Bax and active caspase-3 in the INS-1 cells. The expression of Bcl-2 was reduced significantly in both CsA plus K groups compared with the CsA-alone group. By contrast, the expression levels of Bax and active caspase-3 were reduced in both CsA plus K groups compared with the CsA-only group. Magnifications×400. Relative optical densities of bands in each lane were normalized with each β-actin band from the same gel. #P<0.05 vs. Control or K1 or K10; *P<0.05 vs. CsA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3757011&req=5

pone-0072685-g007: Effect of KRG on apoptotic cell death in INS-1 cells during CsA-induced injury.(A and B) TUNEL staining was used to detect apoptosis, and its quantitative analysis is shown for INS-1 cells treated with either CsA alone or CsA plus 1 or 10 µg/mL of KRG for 24 h. TUNEL-positive nuclei (arrows) were rarely observed in the control group or in those treated with KRG alone. However, the numbers of TUNEL-positive nuclei increased significantly with CsA treatment compared with the control, and the addition of KRG decreased this. (C) Immunoblot analyses for Bcl-2, Bax and active caspase-3 in the INS-1 cells. The expression of Bcl-2 was reduced significantly in both CsA plus K groups compared with the CsA-alone group. By contrast, the expression levels of Bax and active caspase-3 were reduced in both CsA plus K groups compared with the CsA-only group. Magnifications×400. Relative optical densities of bands in each lane were normalized with each β-actin band from the same gel. #P<0.05 vs. Control or K1 or K10; *P<0.05 vs. CsA.
Mentions: To investigate the underlying molecular mechanisms of the antiapoptotic effect of KRG in CsA-induced injury, INS-1 cells were treated with CsA alone or combined with KRG (1 or 10 µg/mL) for 24 h. Figures 7A and 7B show TUNEL staining and its quantitative analysis in the four groups. The number of TUNEL-positive cells increased significantly with CsA treatment compared with the control, but the addition of KRG decreased them (Control, 1.1±0.3; K10, 0.9±0.2; CsA, 35.7±5.2; CsA+K10, 18.2±2.3; CsA vs. control or K10; CsA vs. CsA+K10, P<0.05). Figure 7C shows that CsA suppressed expression of the antiapoptotic marker Bcl-2 but that this suppression was attenuated by cotreatment with KRG. CsA treatment induced the expression levels of the proapoptotic markers Bax and active caspase-3, and these were attenuated by cotreatment with KRG. Thus, KRG had antiapoptotic effects in INS-1 cells during CsA treatment.

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