• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.11
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• pp.1414-1418
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• 2017

Inhibition of advanced glycation end product (AGE) formation is a valuable therapeutic strategy for the regulation of diabetic complications. This study was conducted to identify potential therapeutic targets of anti-diabetic complications from irradiated mangiferin using AGE formation assay. Radiolytic degradation of the xanthone glucoside mangiferin by gamma-irradiation resulted in three degraded mangiferin analogues: mangiferdiol (1), mangiferinol (2), and isomangiferinol (3). Structures of the three newly generated compounds were characterized by interpretation of nuclear magnetic resonance ($^1H$, $^{13}C$ NMR, $^1H-^1H$ COSY, HSQC, HMBC, and NOESY) and mass spectroscopic data. The anti-diabetic complication of the generated mangiferin derivatives were tested using in vitro AGE formation method. Among the tested degraded products, mangiferinol (2) and isomangiferinol (3) exhibited significantly improved potency against AGE formation inhibitory activities with $IC_{50}$ values of $5.6{\pm}0.8$ and $7.6{\pm}0.9{\mu}M$, respectively. This result implies that xanthone derivatives generated from gamma-irradiated mangiferin might be beneficial for prevention of diabetic complication and related diseases.

• Food Science of Animal Resources
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• v.34 no.1
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• pp.127-132
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• 2014

Optimization of carnosine and anserine extraction from chicken breast was performed using response surface methodology (RSM) to obtain the maximized physiological activities for anti-glycation and anti-oxidation. The optimum extraction conditions were water extraction for 1.6 h in the case of the 20-wk laying hen muscle and water extraction for 2.12 h in the case of 90-wk laying hen muscle. Higher carnosine and anserine contents were measured in the 20-wk laying hen muscle, along with higher physiological activities, which increased in direct proportion with the dipeptide contents. The extracts prepared from the 20-wk laying hen under optimum conditions showed 57% inhibition of advanced glycated end-product formation, 64% inhibition of lipid peroxidation, and 61% of DPPH radical scavenging effects. On the other hand, 52% inhibition of AGE formation, 62% inhibition of lipid peroxidation, and 53% of DPPH radical scavenging effect were demonstrated within the 90-wk laying hen. In addition, the ratio of carnosine was a key indicator for the physiological activities of the extracts.

• Natural Product Sciences
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• v.22 no.3
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• pp.175-179
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• 2016

The aim of this study was to evaluate the anti-diabetic effects of the water extract of Lespedeza cuneata (LCW) using rat insulinoma (RIN) m5F cells and streptozotocin (STZ)-induced diabetic rats. The effect of LCW on the protection of pancreatic beta cells was assessed using MTT assay, and nitric oxide production was assessed using Griess reagent. STZ-induced diabetic rats were treated with 100 and 400 mg/kg body weight of LCW for 5 weeks. In results, LCW significantly protected cytokine-induced toxicity and NO production, and increased insulin secretion in RINm5F cells. LCW significantly decreased serum blood glucose, thiobarbituric acid reactive substances (TBARS), blood urea nitrogen (BUN) and advanced glycation end products (AGEs) levels, and renal fibronectin expression in STZ-induced diabetic rats. Also, LCW effectively improved BW loss in STZ-induced diabetic rats. Thus, our results suggest that LCW has a beneficial effect on cytokine-induced pancreatic beta cell damage and biomarkers of diabetic complication in hyperglycemic rats.

• Natural Product Sciences
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• v.27 no.4
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• pp.245-250
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• 2021

The methylglyoxal (MGO) trapping constituents from Malus baccata L. were investigated using incubation of MGO and crude extract under physiological conditions followed by HPLC analysis. The peak areas of MGO trapping compounds decreased, and their chemical structures were identified by HPLC-ESI/MS. Sieboldin was identified as a major active molecule representing MGO-trapping activity of the crude extract. After reaction of sieboldin and MGO, remaining MGO was calculated by microplate assay method using imine (Schiff base) formation of 2,4-dinitrophenylhydrazine (DNPH) and aldehyde group. After 4 h incubation, sieboldin trapped over 43.8% MGO at a concentration of 0.33 mM and showed MGO scavenging activity with an RC₅₀ value of 0.88 mM for the incubation of 30 min under physiological conditions. It was also confirmed that sieboldin inhibited the production of advanced glycation end products (AGE) produced by bovine serum albumins (BSA)/MGO. Additionally, MGO trapping mechanism of sieboldin was more specifically identified by ¹H-, ¹³C-, 2D NMR and, confirm to be attached to the position of C-3' (or 5').

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.389-396
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• 2022

The increased expression of receptors for advanced glycation end-product (RAGE) is known as a key player in the progression of vascular remodeling. However, the precise signal pathways regulating RAGE expression in vascular smooth muscle cells (VSMCs) in the injured vasculatures are unclear. Given the importance of mitogen-activated protein kinase (MAPK) signaling in cell proliferation, we investigated the importance of MAPK signaling in high-mobility group box 1 (HMGB1)-induced RAGE expression in VSMCs. In HMGB1 (100 ng/ml)-stimulated human VSMCs, the expression of RAGE mRNA and protein was increased in association with an increase in AGE-induced VSMC proliferation. The HMGB1-induced RAGE expression was attenuated in cells pretreated with inhibitors for ERK (PD98059, 10 μM) and p38 MAPK (SB203580, 10 μM) as well as in cells deficient in ERK and p38 MAPK using siRNAs, but not in cells deficient of JNK signaling. In cells stimulated with HMGB1, the phosphorylation of ERK, JNK, and p38 MAPK was increased. This increase in ERK and p38 MAPK phosphorylation was inhibited by p38 MAPK and ERK inhibitors, respectively, but not by JNK inhibitor. Moreover, AGE-induced VSMC proliferation in HMGB1-stimulated cells was attenuated in cells treated with ERK and p38 MAPK inhibitors. Taken together, our results indicate that ERK and p38 MAPK signaling are involved in RAGE expression in HMGB1-stimulated VSMCs. Thus, the ERK/p38 MAPK-RAGE signaling axis in VSMCs was suggested as a potential therapeutic target for vascular remodeling in the injured vasculatures.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.13.1-13.15
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• 2018

Wound healing is delayed in diabetic patients. Increased apoptosis and endothelial progenitor cell (EPC) dysfunction are implicated in delayed diabetic wound healing. Melatonin, a major secretory product of the pineal gland, promotes diabetic wound healing; however, its mechanism of action remains unclear. Here, EPCs were isolated from the bone marrow of mice. Treatment of EPCs with melatonin alleviated advanced glycation end product (AGE)-induced apoptosis and cellular dysfunction. We further examined autophagy flux after melatonin treatment and found increased light chain 3 (LC3) and p62 protein levels in AGE-treated EPCs. However, lysosome-associated membrane protein 2 expression was decreased, indicating that autophagy flux was impaired in EPCs treated with AGEs. We then evaluated autophagy flux after melatonin treatment and found that melatonin increased the LC3 levels, but attenuated the accumulation of p62, suggesting a stimulatory effect of melatonin on autophagy flux. Blockage of autophagy flux by chloroquine partially abolished the protective effects of melatonin, indicating that autophagy flux is involved in the protective effects of melatonin. Furthermore, we found that the AMPK/mTOR signaling pathway is involved in autophagy flux stimulation by melatonin. An in vivo study also illustrated that melatonin treatment ameliorated impaired wound healing in a streptozotocin-induced diabetic wound healing model. Thus, our study shows that melatonin protects EPCs against apoptosis and dysfunction via autophagy flux stimulation and ameliorates impaired wound healing in vivo, providing insight into its mechanism of action in diabetic wound healing.