• Genomics & Informatics
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• v.11 no.4
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• pp.224-229
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• 2013

Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that is able to bind several different ligands, including advanced glycation endproducts, high-mobility group protein (B)1 (HMGB1), S-100 calcium-binding protein, amyloid-${\beta}$-protein, Mac-1, and phosphatidylserine. Its interaction is engaged in critical cellular processes, such as inflammation, proliferation, apoptosis, autophagy, and migration, and dysregulation of RAGE and its ligands leads to the development of numerous human diseases. In this review, we summarize the signaling pathways regulated by RAGE and its ligands identified up to date and demonstrate the effects of hyper-activation of RAGE signals on human diseases, focused mainly on renal disorders. Finally, we propose that RAGE and its ligands are the potential targets for the diagnosis, monitoring, and treatment of numerous renal diseases.

• Journal of Ginseng Research
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• v.39 no.2
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• pp.116-124
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• 2015

Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.187-193
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• 2013

The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-${\alpha}$ and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1305-1313
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• 2009

Saengjihwangeum-ja (SJHEJ) was recorded in DongEuiBoGam as being able to be used for treatment of Sogal whose concept had been applied to Diabetes Mellitus (DM). Modification of proteins by long term circulation of glucose leads to the formation of advanced glycation end product(AGE). Recent immunological studies demonstrated that ligation of AGE play an important role in the development of diabetic complications including atherosclerosis, which includes activation, adhesion, and migration of monocytes. Also, AGE and Maillard reaction product(MRP) could augment monocyte inflammatory responses via ligation of AGE receptor. In this study, the effects of SJHEJ extracts on the expression of inflammatory response-related genes such as tumor necrosis factor-$\alpha$, monocyte chemoattractant protein-1, interferon-g-inducible protein-10, and cyclooxygenase-2 in the human monocyte cell line, THP-1 cells. Reverse transcriptase-polymerase chain reaction revealed that SJHEJ had inhibitory effects on the expression of the TNF-a, MCP-1, IP-10, COX2, IL-1b genes in MRP-induced THP-1 cells. Treatment with SJHEJ had reduced reactive oxygen production in THP-1 cells stimulated by MRP. These inhibitory effects might be exerted via prevention of oxidative stress in activated monocytes. In addition, radical scavenging activity of SJHEJ was increased. These results suggest that SJHEJ has a beneficial effects for improve diabetic vascular complication.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.133-145
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• 2008

Objectives: The aim of present study was to investigate recovery effects of Hirudo, which has been used clinically in diabetes therapy. Methods: We established three groups: normal, control, Hirudo, and assigned 6 rats to each group. The normal group was not treated by any process and fed by normal saline. The control & Hirudo groups were administered streptozotocin (STZ) to induce diabetes. Hirudo extract was orally administered to the Hirudo group for 10 days. After 8 weeks, the rats were sacrificed and their body weight, 24hrs urinary protein excretion, glucose, albumin, BUN, creatinine, total-cholesterol, LDL-cholesterol, triglyceride in blood, and level of glycation end-product (AGE) and transforming growth factor (TGF-${\beta}1$) in serum were measured. Morphological profiles and morphometric studies of the kidney cortex, renal transforming growth factor (TGF-${\beta}1$) expression, and renal receptor for advanced glycation end-products (RAGE) expression were studied. Results: The following results were obtained. The protein amount in urine per 24hrs of the Hirudo-treated group as compared to the control group was significantly reduced. The BUN and creatinine level in serum of the Hirudo-treated group as compared to the control group was significantly inhibited. The construction change in kidney of the Hirudo-treated group as compared to the control group was significantly inhibited. The factor of the Hirudo-treated group as compared to the control group was significantly inhibited, which induced the construction change in kidney. Conclusions: The above results suggest that Hirudo partially improved the function of the kidney.