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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

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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.


Distribution of activated nuclear factor-kappaB (NF-κB) in the retinal microvascular cells detected by immunohistochemistry. (A) Representative photomicrographs of retinal microvasculatures from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Positive signals (arrow) for activated NF-κB were mainly detected in the nuclei of the diabetic retinal microvascular cells. 400× magnification; (B) Quantitative analysis of the positive cells in the retinal microvascular. The values in the bar graphs represent the mean ± 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-f006: Distribution of activated nuclear factor-kappaB (NF-κB) in the retinal microvascular cells detected by immunohistochemistry. (A) Representative photomicrographs of retinal microvasculatures from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Positive signals (arrow) for activated NF-κB were mainly detected in the nuclei of the diabetic retinal microvascular cells. 400× magnification; (B) Quantitative analysis of the positive cells in the retinal microvascular. The values in the bar graphs represent the mean ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.

Mentions: The transcription factor NF-κB is a common component of the downstream signal pathway of AGEs [36]. NF-κB also plays a key role in apoptosis [37,38]. Therefore, we evaluated the activation of NF-κB in the retinal microvascular cells with immunohistochemistry. Marked NF-κB activity was mainly found in the nuclei of the retinal microvascular cells of the diabetic rats (Figure 6A). However, in the normal rats, positive signals for activated NF-κB were rarely detected. AKE significantly inhibited the expression of activated NF-κB compared with the expression in diabetic rats (Figure 6B, 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
Distribution of activated nuclear factor-kappaB (NF-κB) in the retinal microvascular cells detected by immunohistochemistry. (A) Representative photomicrographs of retinal microvasculatures from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Positive signals (arrow) for activated NF-κB were mainly detected in the nuclei of the diabetic retinal microvascular cells. 400× magnification; (B) Quantitative analysis of the positive cells in the retinal microvascular. The values in the bar graphs represent the mean ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-08-00585-f006: Distribution of activated nuclear factor-kappaB (NF-κB) in the retinal microvascular cells detected by immunohistochemistry. (A) Representative photomicrographs of retinal microvasculatures from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE). Positive signals (arrow) for activated NF-κB were mainly detected in the nuclei of the diabetic retinal microvascular cells. 400× magnification; (B) Quantitative analysis of the positive cells in the retinal microvascular. The values in the bar graphs represent the mean ± the SEM, n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
Mentions: The transcription factor NF-κB is a common component of the downstream signal pathway of AGEs [36]. NF-κB also plays a key role in apoptosis [37,38]. Therefore, we evaluated the activation of NF-κB in the retinal microvascular cells with immunohistochemistry. Marked NF-κB activity was mainly found in the nuclei of the retinal microvascular cells of the diabetic rats (Figure 6A). However, in the normal rats, positive signals for activated NF-κB were rarely detected. AKE significantly inhibited the expression of activated NF-κB compared with the expression in diabetic rats (Figure 6B, 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.