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The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

View Article: PubMed Central - PubMed

ABSTRACT

Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells.

No MeSH data available.


Immunohistochemical localization of the advanced glycation end products (AGEs). (A) Representative immunostaining of AGEs in the retinal capillaries of normal rats (NOR), STZ-treated diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Strong immunoreactivity for AGEs was observed in the cytoplasm of the diabetic retinal microvascular cells. In contrast, immunoreactivity in the capillary cells of the AKE-treated diabetic rats was decreased. 400× magnification; (B) Quantitative analysis of the AGEs immunoreactive intensities. The values in the bar graphs represent the means ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
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nutrients-08-00585-f004: Immunohistochemical localization of the advanced glycation end products (AGEs). (A) Representative immunostaining of AGEs in the retinal capillaries of normal rats (NOR), STZ-treated diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Strong immunoreactivity for AGEs was observed in the cytoplasm of the diabetic retinal microvascular cells. In contrast, immunoreactivity in the capillary cells of the AKE-treated diabetic rats was decreased. 400× magnification; (B) Quantitative analysis of the AGEs immunoreactive intensities. The values in the bar graphs represent the means ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.

Mentions: To investigate AGE formation and accumulation in the retinal microvascular cells, immunohistochemical staining for AGEs was performed on the retinal trypsin digests. In the normal rats, only weak staining for AGEs was present within the retinal microvascular cells. In the diabetic rats, a striking increase in immunoreactive straining for AGEs was observed in the cytoplasm of the retinal microvascular cells (Figure 4A). The treatment of the diabetic rats with AKE reduced the AGEs deposited in the retinal microvascular cells. Morphometric analysis revealed that the intensity of AGE immunolabeling was significantly increased by 5-fold in diabetic rats compared with the normal rats (Figure 4B, p < 0.01), and this increase was suppressed by treatment with AKE (Figure 4B, p < 0.01).


The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction
Immunohistochemical localization of the advanced glycation end products (AGEs). (A) Representative immunostaining of AGEs in the retinal capillaries of normal rats (NOR), STZ-treated diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Strong immunoreactivity for AGEs was observed in the cytoplasm of the diabetic retinal microvascular cells. In contrast, immunoreactivity in the capillary cells of the AKE-treated diabetic rats was decreased. 400× magnification; (B) Quantitative analysis of the AGEs immunoreactive intensities. The values in the bar graphs represent the means ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037569&req=5

nutrients-08-00585-f004: Immunohistochemical localization of the advanced glycation end products (AGEs). (A) Representative immunostaining of AGEs in the retinal capillaries of normal rats (NOR), STZ-treated diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Strong immunoreactivity for AGEs was observed in the cytoplasm of the diabetic retinal microvascular cells. In contrast, immunoreactivity in the capillary cells of the AKE-treated diabetic rats was decreased. 400× magnification; (B) Quantitative analysis of the AGEs immunoreactive intensities. The values in the bar graphs represent the means ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
Mentions: To investigate AGE formation and accumulation in the retinal microvascular cells, immunohistochemical staining for AGEs was performed on the retinal trypsin digests. In the normal rats, only weak staining for AGEs was present within the retinal microvascular cells. In the diabetic rats, a striking increase in immunoreactive straining for AGEs was observed in the cytoplasm of the retinal microvascular cells (Figure 4A). The treatment of the diabetic rats with AKE reduced the AGEs deposited in the retinal microvascular cells. Morphometric analysis revealed that the intensity of AGE immunolabeling was significantly increased by 5-fold in diabetic rats compared with the normal rats (Figure 4B, p < 0.01), and this increase was suppressed by treatment with AKE (Figure 4B, p < 0.01).

View Article: PubMed Central - PubMed

ABSTRACT

Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-&kappa;B) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-&kappa;B and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-&kappa;B activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells.

No MeSH data available.