• Journal of Korean Neurosurgical Society
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• 제59권3호
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• pp.259-268
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• 2016

Objective : Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. Methods : HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. Results : AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. Conclusion : Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.

• Food Science and Biotechnology
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• 제18권1호
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• pp.190-196
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• 2009

The inhibition effects of an Alpinia officinarum (AO, Zingiberaceae) on the formation of advanced glycation end products, aldose reductase, and scavenging effect on 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical for the prevention and/or treatment of diabetic complications were investigated. The ethyl acetate fraction of AO was the most effective among all fractions. Through the tests with electron impact-mass spectrometry and nuclear magnetic resonance, two compounds (compound 1 and 2) finally obtained from the ethyl acetate fraction of AO were identified as galangin (1) and kaempferide (2), respectively. In addition, the compound 1 and 2 and the ethyl acetate fraction were compared for the prevention effect on advanced glycation end products, aldose reductase, and the scavenging effect on DPPH radical. The ethyl acetate fraction was significantly more effective than the 2 compounds for those preventive activities.

• 생약학회지
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• 제37권4호
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• pp.307-313
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• 2006

Reactive oxygen species (ROS) and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic nephropathy by hyperglycemia. To find natural agents improving diabetic nephropathy, 63 natural resources which used to the treatment of diabetes mellitus in a folk remedy were investigated with an in vitro system employing radical scavenging activity and inhibitory activity of AGEs formation. In results, the extracts of Aspalathus linearis, Rubus coreanus, Rosa rugosa, and Epimedium koreanum significantly inhibited the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with $IC_{50}$ values less than $10{\mu}g/ml$. The extracts of Zea mays, Cucurbita moschata, Cudrania tricuspidata, and Aspalathus linearis effectively reduced the formation of AGEs compared with the positive control $N-acetyl-_L-cystenine$ (NAC) and aminoguanidine (AG). In addition, the extracts of Aspalathus linearis, Commelina communis, Cornus officinalis, and Lespodeza cuneata showed the all inhibitory activity against DPPH radical and AGEs formation. Also, these resources definitely showed the radical scavenging activity against peroxynitrite $(ONOO^-)$ and hydroxyl radical $({\cdot}OH)$ relating to high glucose-induced ROS production. Thus, these results suggest that some natural resources may regulate the initiation and progression of diabetic nephropathy through inhibition of ROS production and AGEs formation.

• 생약학회지
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• 제46권3호
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• pp.260-267
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• 2015

Advanced glycation end products (AGEs) have been postulated to play a central role in the development of diabetic complications. A variety of different agents that inhibit AGEs have been under investigation. In this study, 111 herbal medicines from China have been investigated with an in vitro evaluation system using AGEs formation inhibitory activity. Of these, 9 herbal medicines (IC₅₀: <5 μg/ml) were found to have significant AGEs formation inhibitory activity. Particularly, herbal medicines Barleria cristata (leaves), Calotropis gigantea (stems), Ardisia virens (leaves), Dalbergia yunnanensis (leaves) Pittosporum runcatum (leaves), Ardisia japonica (leaves), Rhododendron racemosum (twigs), Oxyria sinensiss (aerial parts), Pyrrosia calvata (whole plants), showed more potent inhibitory activity (approximately 15-40 fold) than the positive control aminoguanidine (IC₅₀: 76.47 μg/ml).

• 생약학회지
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• 제46권3호
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• pp.250-259
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• 2015

Advanced glycation end products (AGEs) have been implicated in diabetic complications. In this study, the inhibitory effect on AGEs formation of 156 Korean herbal medicines has been evaluated. Among them, 15 Korean herbal medicines were showed to have significant effect (IC₅₀: <10 μg/ml) compared to positive reference, aminoguandine (IC₅₀: 76.47±4.81 μg/ml). Especially, four herbal medicines, Alnus firma (leaves, IC₅₀: 3.25±0.10 μg/ml), Juncus decipiens (whole plants, IC₅₀: 4.30±0.44 μg/ml), Smilax china (stems, IC₅₀: 3.55±0.21 μg/ml), and Vicia amoena (Aerial parts, IC₅₀: 4.25±0.06 μg/ml) showed more potent inhibitory activity approximately 8-24 fold) than the positive control aminoguanidine.

• 생약학회지
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• 제46권3호
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• pp.268-278
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• 2015

In this study, 80 herbal medicines from Vietnam have been investigated with an in vitro evaluation system using advanced glycation end products (AGEs) formation inhibitory activity. Of these, 10 herbal medicines (IC₅₀: <5 μg/ml) were found to have significant AGEs formation inhibitory activity. Particularly, herbal medicines Strobilanthes pateriformis (aerial parts), Rhodamnia dumetorum (twigs), Glochidion rubrum (twigs), Dipterocarpus obtusifolius (twigs), Bombax ceiba (twigs), Amesiodendron chinense (twigs), Bauhinia coccinea (twigs), Lithocarpus laouanensis (twigs), Bauhinia bracteata (twigs) and Connarus paniculatus (twigs), showed more potent inhibitory activity (approximately 16-31 fold) than the positive control aminoguanidine (IC₅₀: 76.47 μg/ml).

• 생약학회지
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• 제40권4호
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• pp.388-393
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• 2009

Advanced glycation end products (AGEs) have been implicated in the development of diabetic complications. The AGEs inhibitors or cross-link breakers attenuate various functional and structural manifestations of diabetic complications. In this study, 64 herbal medicines from China and Vietnam have been investigated with an in vitro evaluation system using AGEs inhibitory activity. Of these, eight herbal medicines ($IC_{50}$<50 ${\mu}g$/ml) were found to have strong AGEs inhibitory activity compared with aminoguanidine (14 days, $IC_{50}$=75.98 ${\mu}g$/ml; 28 days, $IC_{50}$=88.27 ${\mu}g$/ml). Particularly, four herbal medicines, Buddleja officinalis (whole plant), Syzygium cuminii (leaf), Eugenia caryophyllate (seed), and Paeonia suffruticosa (root) showed more potent inhibitory activity (approximately 5-6 fold) than the positive control aminoguanidine.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.193-201
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• 2018

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

• 생약학회지
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• 제33권4호통권131호
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• pp.308-311
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• 2002

Advanced glycation end products(AGEs) are largly involved in the pathogenesis of diabetic nephropathy. It is obvious that inhibition of AGEs formation is important in preventing the occurrence and progression of diabetic nephropathy. In diabetes, this reaction is greatly accerated and is important in the pathogenesis of diabetic complications, especially diabetic nephropathy. Therefore, to seek possible AGEs inhibitors in herbal medicines, unprocessed - and processed Magnolia Bark were examined in vitro as basic data for aniaml experiment. The content of magnolol in unprocessed Magnolia Bark was $0.796{\pm}0.072%$, and after processing was decreased to $0.586{\pm}0.101%(p<0.01)$. The content of AGEs was measured by their intrinsic fluorescence. The $IC_{50}({\mu}g/ml)$ values of aminoguanidine, unprocessed- and procesled Magnolia Bark are $38.845{\pm}8.36{\mu}g/ml$, $54.264{\pm}3.153{\mu}g/ml$ and $27.882{\pm}1.836{\mu}g/ml$, respectively. This result means that prcessed Magnolia Bark was more effective than aminoguanidine, as positive control.

• 생약학회지
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• 제39권3호
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• pp.223-227
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• 2008

Advanced glycation end products (AGEs) contribute to the progression of micro and macrovsacular complication of diabetes and therefore present a promising target for therapeutic agents. In this study, 40 Korean herbal medicines have been investigated with an in vitro evaluation system using AGEs inhibitory activity. Of these, 21 herbal medicines $(IC_{50}<50{\mu}g/ml)$ exhibited an inhibitory activity against AGEs formation compared with anminoguanidine $(IC_{50}=72.12{\mu}g/ml)$. Particularly, 7 herbal medicines, Actinidia arguta (root and stem), Crataegus pinnatifida (twig), Camellia japonica (whole), Kalopanax pictus (bark), Lagerstroemia indica (leaf-stem), Reynoutria sachalinensis (root) showed more potent inhibitory activity (approximately 3-10 fold) than the positive control aminoguanidine.