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Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-κB pathway activation in human umbilical vein endothelial cells
- Source :
- Journal of ethnopharmacology. 148(1)
- Publication Year :
- 2012
-
Abstract
- Ethnopharmacological relevance Licorice (Glycyrrhiza uralensis roots) is used as a traditional medicine for the treatment of diabetes mellitus and its vascular complications. Glycyrrhizic acid (GA, also known as Glycyrrhizin), a triterpenoid saponin glycoside, is considered to be a bioactive component in Licorice and is beneficial to diabetic vascular complications. Aim of study The present study was conducted to evaluate the potential protective activities on AGEs-induced endothelial dysfunction, including anti-apoptosis, antioxidant stress and anti-proinflammatory responses, and explore the underlying mechanism. Materials and methods Human umbilical vein endothelial cells (HUVECs) were incubated and pre-treated with GA (10−9–10−6 M) or RAGE-Ab (5 μg/ml) in the presence or absence of 200 μg/ml AGEs. AO/EB fluorescence staining assay was performed to evaluate anti-apoptosis activity. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in cell supernatant were detected by kits while the intracellular reactive oxygen species (ROS) generation was determined by 2,7-dichlorodihydrofluorescin diacetate (DCFH-DA) kit. Immunocytochemistry analysis was designed to determine transforming growth factor beta1(TGF-β1) protein expression while immunofluorescence analysis for RAGE and NF-kB. The protein expressions of TGF-β1, RAGE and NF-kB were analyzed by Western blot analysis. Results Pretreatment with GA at a concentration of 10−8–10−6 M significantly reduced the AGEs-induced apoptosis in HUVECs. GA significantly increased antioxidant enzyme SOD activity and decreased peroxide degradation product MDA level in a dose-dependent manner. Furthermore, GA also remarkably inhibited the overgeneration of AGEs-induced ROS. Both immunocytochemistry analysis and western blot analysis showed that GA significantly decreased the protein expression of poinflammatory cytokine TGF-β1 in a similar manner which RAGE-Ab did. Additionally, AGEs-induced RAGE and NF-kB protein expressions were down-regulated significantly by the pretreatment with GA or RAGE-Ab. Conclusion These findings provide evidences that GA possesses protective activity on AGEs-induced endothelial dysfunction, including anti-apoptosis, anti-inflammation and antioxidant stress, via inhibiting RAGE/NF-kB pathway. GA might be an alternative for the prevention and treatment of diabetic vascular complications in an appropriate dosage.
- Subjects :
- Glycation End Products, Advanced
medicine.medical_specialty
Receptor for Advanced Glycation End Products
Anti-Inflammatory Agents
Apoptosis
Pharmacology
Umbilical vein
Antioxidants
RAGE (receptor)
Superoxide dismutase
chemistry.chemical_compound
Western blot
Internal medicine
Malondialdehyde
Drug Discovery
medicine
Human Umbilical Vein Endothelial Cells
Humans
Endothelial dysfunction
Glycyrrhizin
Cells, Cultured
medicine.diagnostic_test
biology
business.industry
Superoxide Dismutase
NF-kappa B
medicine.disease
Glycyrrhizic Acid
Endocrinology
chemistry
biology.protein
business
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 18727573
- Volume :
- 148
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of ethnopharmacology
- Accession number :
- edsair.doi.dedup.....7e3de62b7bb859318a8fd908a763264f