• Korean Journal of Pharmacognosy
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• v.44 no.3
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• pp.305-311
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• 2013

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, 54 herbal medicines from China have been investigated with an in vitro evaluation system using AGEs formation inhibitory activity. Of these, 6 herbal medicines ($IC_{50}<5{\mu}g/ml$) were found to have significant AGEs formation inhibitory activity. Particularly, herbal medicines Punica granatum (peels), Terminalia chebula (fruits), Rheum palmatum (roots), Oxyria digyna (stems and leaves), Anisodus luridus (roots) and Quercus schottkyana(stems and leaves) showed more potent inhibitory activity (approximately 9-43 fold) than the positive control aminoguanidine ($IC_{50}=77.04{\mu}g/ml$).

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.383.2-383.2
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• 2002

Diabetic nephropathy is major chronic complication of diabetes mellitus. Advanced glycation endproducts(AGEs) are largely involved in the pathogenesis of diabetic nephropathy. The irreversibly formed AGEs do not return to normal even if hyperglycemia is corrected and continue to accumulate over the lifetime of protein. The AGEs inhibitor. aminoguanidine(AG), is the only protein glycation inhibitor currently under development. its safety however is desirable. To find possible AGEs inhibitor in herbal medicines, bovine serum albumin was added to a mixture of sugars and some of processed. unprocessed herbal medicines or AG. Cyperi rhizoma was processed in four different methods according to chinese pharmacopoeia and traditional literatures. In comparision to the negative control with no inhibitor and positive control with AG. alcoholic extracts of these processed cyperi rhizoma proved to have more potent inhibitory activities than that of unprocessed cyperi rhizoma. These results revealed that some processed herbal medicines have a more potent in vitro inhibitory action on AGEs formation than AG. suggesting the possible candidate for diabetic nephropathy from the processed herbal medicines.

• Parasites, Hosts and Diseases
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• v.42 no.4
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• pp.175-183
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• 2004

To evaluate the role of nitric oxide (NO) in $IFN-{\gamma}$ production and apoptosis of splenocytes in genetically different strains of mice with toxoplasmosis, BALB/c (a toxoplasmosis resistant strain) and C57BL/6 (a toxoplasmosis susceptible strain) mice were infected with Toxoplasma gondii cysts orally and subsequently injected intraperitoneally with aminoguanidine, an iNOS inhibitor (AG; 35 mg/kg per mouse daily for 14 days). When BALB/c or C57BL/6 mice were infected with T. gondii without AG treatment, number of brain cysts, NO and IFN-y production by splenocytes, and percentages of apoptotic splenocytes were increased compared to uninfected control mice without AG treatment. AG treatment increased the number of brain cysts, and reduced NO and $IFN-{\gamma}$ production in T. gondii-infected C57BL/6 mice. In contrast, in T. gondii-infected BABL/c mice, the number of brain cysts, and NO and $IFN-{\gamma}$ production of splenocytes was not altered by treatment with AG. However, the percentages of apoptotic splenocytes in T. gondii-infected BALB/c or C57BL/6 mice were not affected by AG treatment. These results suggest that NO modulates $IFN-{\gamma}$ production in T. gondii-infected C57BL/6 mice, and that NO is involved in mediating a protective response in toxoplasmosis susceptible, but not resistant, mice strain during acute infection.

• Korean Journal of Pharmacognosy
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• v.44 no.4
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• pp.372-378
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• 2013

In this study, the inhibitory effect on advanced glycation end products (AGEs) formation of 43 Korean herbal medicines has been evaluated. Among them, 16 Korean herbal medicines were showed to have significant effect ($IC_{50}$; <50 ${\mu}g/ml$) compared to positive reference, aminoguandine ($IC_{50}$: $76.47{\pm}4.81{\mu}g/ml$). Especially, five herbal medicines, Rubus coreanus (leaves, $IC_{50}$: $4.49{\pm}0.03{\mu}g/ml$), Rubus coreanus (twigs, $IC_{50}$: $3.80{\pm}0.34{\mu}g/ml$), Ampleopsis brevipedunculata (stems, $IC_{50}$: $7.43{\pm}0.09{\mu}g/ml$), Lindera erythrocarpa (leave, $IC_{50}$: $8.14{\pm}0.20{\mu}g/ml$), and Lindera erythrocarpa (stems, $IC_{50}$: $3.69{\pm}0.14{\mu}g/ml$) showed more potent inhibitory activity (approximately 9-20 fold) than the positive control aminoguanidine.

• Korean Journal of Pharmacognosy
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• v.47 no.4
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• pp.312-318
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• 2016

Advanced glycation end products (AGEs) such as $N^{\varepsilon}$-(carboxy-methyl)lysine (CML) have been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the inhibitory effects of ethanolic extract of Aster koraiensis (AKE) on AGEs formation and AGEs-collagen cross-linking in vitro and CMLs formation in streptozotocin (STZ)-induced diabetic rats. AKE significantly inhibited AGEs formation ($IC_{50}$ value of $18.74{\mu}g/mL$) and AGEs-collagen cross-linking ($IC_{50}$ value of 0.274 mg/mL) in vitro than the well-known glycation inhibitor aminoguanidine ($IC_{50}$ value of $72.12{\mu}g/mL$ and 1.99 mg/mL, respectively). AKE (100 mg/kg per day) was given to diabetic rats for 9 weeks. In STZ-induced diabetic rats, severe hyperglycemia was developed, and urinary CMLs and plasma CMLs were markedly increased. Immunohistochemical stain revealed that CMLs were accumulated within renal glomerulus in STZ-induced diabetic rats. However, AKE significantly reduced urinary CMLs and plasma CMLs in diabetic rats. CMLs accumulation was inhibited by AKE treatment in the renal glomerulus. These results suggest that AKE had an inhibitory effect of AGE accumulation in the glomeruli of diabetic rat and could be an inhibitor of AGE-induced protein cross-linking. The oral administration of AKE may significantly help to prevent the progression of diabetic nephropathy in patients with diabetes.

• Applied Biological Chemistry
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• v.51 no.4
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• pp.316-320
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• 2008

Ten compounds, (+)-pinoresinol (1), (-)-balanophonin (2), gallicin (3), vanillin (4), 4-hydroxybenzaldehyde (5), coniferaldehyde (6), betulinic acid (7), ursolic acid (8), 5-hydroxymethyl furfural (9), and malic acid (10), were isolated from a EtOAc-soluble fraction of the seeds of Cornus officinalis. The structures of these compounds were elucidated by spectroscopic methods as well as by comparison with reported values. Compounds 1, 2, and 4-7 were isolated from this species for the first time. All the isolates (1-10) were subjected to an in vitro bioassay to evaluate their inhibitory activity against advanced glycation end products (AGEs) formation. Among these, compounds 2 and 3 showed the significant inhibitory activity on AGEs formation with $IC_{50}$ values of 27.81 and 18.04${\mu}M$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.481-487
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• 2014

Ischemic postconditioning (IPost) could decrease ischemia-reperfusion (IR) injury. It has not yet reported whether IPost is useful when ischemic heart disease is accompanied with co-morbidities like hyperthyroidism. The aim of this study was to examine the effect of IPost on myocardial IR injury in hyperthyroid male rats. Hyperthyroidism was induced with administration of thyroxine in drinking water (12 mg/L) over a period of 21 days. After thoracotomy, the hearts of control and hyperthyroid rats were perfused in the Langendorff apparatus and subjected to 30 minutes global ischemia, followed by 120 minutes reperfusion; IPost, intermittent early reperfusion, was induced instantly following ischemia. In control rats, IPost significantly improved the left ventricular developed pressure (LVDP) and ${\pm}dp/dt$ during reperfusion (p<0.05); however it had no effect in hyperthyroid rats. In addition, hyperthyroidism significantly increased basal $NO_x$ (nitrate+nitrite) content in serum ($125.5{\pm}5.4{\mu}mol/L$ vs. $102.8{\pm}3.7{\mu}mol/L$; p<0.05) and heart ($34.9{\pm}4.1{\mu}mol/L$ vs. $19.9{\pm}1.94{\mu}mol/L$; p<0.05). In hyperthyroid groups, heart $NO_x$ concentration significantly increased after IR and IPost, whereas in the control groups, heart $NO_x$ were significantly higher after IR and lower after IPost (p<0.05). IPost reduced infarct size (p<0.05) only in control groups. In hyperthyroid group subjected to IPost, aminoguanidine, an inducible nitric oxide (NO) inhibitor, significantly reduced both the infarct size and heart $NO_x$ concentrations. In conclusion, unlike normal rats, IPost cycles following reperfusion does not provide cardioprotection against IR injury in hyperthyroid rats; an effect that may be due to NO overproduction because it is restored by iNOS inhibition.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.587-595
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• 2003

The aim of this study was to investigate trazodone's effect on vasorelaxation and blood pressure lowering and to examine its underlying mechanism of action in isolated thoracic aorta and anesthesized rats. Precontracted aortic rings with high KCl were relaxed with trazodone, at concentrations of $50{\mu}M$ or greater. However, precontracted rings with phenylephrine (PE) were relaxed with trazodone, at concentrations of $0.03{\mu}M$ or greater, in a concentration-dependent manner. These relaxant effects of trazodone on endothelium intact rat aortic rings were significantly greater than those on denuded rings. The trazodone-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-L-arginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a $Ca^{2+}$-activated $K^+$ channel blocker, tetrabutylammonium (TBA), a $Ca^{2+}$ channel blocker, nifedipine, $Na^+$ channel blockers, lidocaine and procaine, and removal of extracellular $Na^+$, but not by aminoguanidine, 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC), indomethacin, glibenclamide and clotrimazole. In vivo, infusion of trazodone elicited significant decrease in arterial blood pressure. Trazodone-induced decrease in blood pressure was markedly inhibited by pretreatment of intravenous injection of saponin, L-NNA, methylene blue, TBA, lidocaine or nifedipine. These findings suggest that the endothelium-dependent relaxation and decrease in blood pressure induced by trazodone is mediated by release of NO from the endothelium, activation of TBA-sensitive $Ca^{2+}$-activated $K^+$ channels or inhibition of $Ca^{2+}$ entry through voltage-gated channel.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.597-606
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• 2003

Although the antidepressant effects of imipramine (IMI) have been well known in several studies, the effects on cardiovascular system, particularly the vasorelaxant effects, have not known clearly. We hypothesis that IMI-induced vasorelaxation involves NO (nitrie oxide), activation of guanylate cyclase (GC) and $Ca^{2+}$ channel. The possible roles of the endothelium and $Ca^{2+}$ in IMI-induced responses were investigated using isolated rings of rat thoracic aorta and anesthesized rats. In KCl-precontracted rings. IMI produces endothelium-dependent and endothelium-independent relaxations in intact (+E) as well as endothelium-denuded (-E) rat aorta in a concentration-dependent manner. In phenylephrine (PE)-precontracted rings, the IMI-induced relaxation was significantly greater in +E rings. The IMI-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, a non-selective GC inhibitor, methylene blue, $Na^+$ channel blockers, lidocaine and procaine, or $Ca^{2+}$ channel blockers, nifedipine and verapamil, in PE-precontracted +E rings, but not in PE-precontracted -E rings. These relaxations were also suppressed by lidocaine or procaine in -E aortic rings. However, IMI-induced relaxations were not inhibited by a PLC inhibitor 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC), an inositol monophosphatase inhibitor, lithium, indomethacin and dexamethasone in +E and -E rings. In vivo, infusion of IMI elicited significant decrease in arterial blood pressure. After intravenous injection of saponin, NOS inhibitors. MB and nifedipine, infusion of IMI inhibited the IMI-lowered blood pressure markedly. These findings suggest that the endothelium-dependent relaxation induced by IMI is mediated by activation of NO/cGMP signaling cascade or inhibition of $Ca^{2+}$ entry through voltage-gated channel, and this mechanism may contribute to the hypotensive effects of IMI in rats.

• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.354-363
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• 2009

Cytotoxic Nitric oxide (NO) overproduced by inducible NO Synthase (iNOS or NOS2), which was induced in inflammatory reactions and immune responses directly or indirectly affects the functions as host defense and can cause normal tissue damage. Microarray analysis was performed to identify gene profiles of both NO-dependent and -independent transcripts in RAW 264.7 macrophages that use selective NOS2 inhibitors aminoguanidine ($100\;{\mu}M$) and L-canavanine (1 mM). A total of 3,297 genes were identified that were up- or down-regulated significantly over 2-fold in lipopolysaccharide (LPS)-treated macrophages. NO-dependency was determined in the expressed total gene profiles and also within inflammatory conditions-related functional categories. Out of all the gene profiles, 1711 genes affected NO-dependently and -independently in 567 genes. In the categories of inflammatory conditions, transcripts of 16 genes (Pomp, C8a, Ifih1, Irak1, Txnrd1, Ptafr, Scube1, Cd8a, Gpx4, Ltb, Fasl, Igk-V21-9, Vac14, Mbl1, C1r and Tlr6) and 29 geneas (IL-1beta, Mpa2l, IFN activated genes and Chemokine ligands) affected NO-dependently and -independently, respectively. This NO dependency can be applied to inflammatory reaction-related functional classifications, such as cell migration, chemotaxis, cytokine, Jak/STAT signaling pathway, and MAPK signaling pathway. Our results suggest that LPS-induced gene transcripts in inflammation or infection can be classified into physiological and toxic effects by their dependency on the NOS2-mediated NO release.