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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.


Apoptosis in the retinal capillaries. The trypsin-digested retinas from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE) were stained with (A) Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL; green) and (B) cleaved caspase-3 (red). 400× magnification. Quantitative analysis of (C) TUNEL-positive nuclei and (D) caspase-3-positive cells. All data are expressed as the mean ± the standard error of the mean (SEM), n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
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nutrients-08-00585-f003: Apoptosis in the retinal capillaries. The trypsin-digested retinas from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE) were stained with (A) Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL; green) and (B) cleaved caspase-3 (red). 400× magnification. Quantitative analysis of (C) TUNEL-positive nuclei and (D) caspase-3-positive cells. All data are expressed as the mean ± the standard error of the mean (SEM), n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.

Mentions: To characterize the death of retinal vascular cells, we applied the TUNEL assay and cleaved caspase-3 immunostaining. In the retinal trypsin digests of normal rats, barely any TUNEL-positive cells were observed. In the diabetic group, many TUNEL-positive microvascular cells and numerous fragmented nuclei were observed in the retinal trypsin digests (Figure 3A). Similarly, enhanced caspase-3-positive cells were observed in the retinal capillaries of the diabetic rats (Figure 3B). However, the treatment with AKE in the diabetic rats prevented the increase in positive cells and resulted in a level similar to that observed in the normal rats (Figure 3C,D).


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
Apoptosis in the retinal capillaries. The trypsin-digested retinas from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE) were stained with (A) Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL; green) and (B) cleaved caspase-3 (red). 400× magnification. Quantitative analysis of (C) TUNEL-positive nuclei and (D) caspase-3-positive cells. All data are expressed as the mean ± the standard error of the mean (SEM), n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-08-00585-f003: Apoptosis in the retinal capillaries. The trypsin-digested retinas from normal rats (NOR), STZ-induced diabetic rats (STZ) and AKE-treated diabetic rats (AKE) were stained with (A) Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL; green) and (B) cleaved caspase-3 (red). 400× magnification. Quantitative analysis of (C) TUNEL-positive nuclei and (D) caspase-3-positive cells. All data are expressed as the mean ± the standard error of the mean (SEM), n = 8. * p < 0.01 vs. normal rats, #p < 0.01 vs. STZ-induced diabetic rats.
Mentions: To characterize the death of retinal vascular cells, we applied the TUNEL assay and cleaved caspase-3 immunostaining. In the retinal trypsin digests of normal rats, barely any TUNEL-positive cells were observed. In the diabetic group, many TUNEL-positive microvascular cells and numerous fragmented nuclei were observed in the retinal trypsin digests (Figure 3A). Similarly, enhanced caspase-3-positive cells were observed in the retinal capillaries of the diabetic rats (Figure 3B). However, the treatment with AKE in the diabetic rats prevented the increase in positive cells and resulted in a level similar to that observed in the normal rats (Figure 3C,D).

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.