• Korean Journal of Pharmacognosy
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• v.42 no.2
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• pp.161-168
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• 2011

Advanced glycation end products (AGEs) has been shown to play an important role in the development of the diabetic complications. The AGEs inhibitors or cross-link breakers attenuate various functional and structural manifestations of diabetic complications. In this study, 69 China herbal medicines have been investigated with an in vitro evaluation system using AGEs inhibitory activity. Of these, 28 herbal medicines $IC_{50}$=<50 ${\mu}g/ml$) were found to have stronger AGEs inhibitory activity compared with aminoguanidine ($IC_{50}$=59.77 ${\mu}g/ml$). Particularly, 5 herbal medicines, Camptotheca acuminata (stem, leaf), Eurya groffii (stem, leaf), Cornus Capitata (leaf), Mucuna birdwoodiana (root), Nelumbo nucifera (fruit, seed) showed more potent inhibitory activity (approximately 6-27 fold) than the positive control aminoguanidine.

• Journal of Nutrition and Health
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• v.49 no.4
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• pp.233-240
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• 2016

Purpose: Diabetic complications are a major concern to manage progression of diabetes. Production of advanced glycation end products (AGEs) due to high blood glucose is one of the mechanisms leading to diabetic complications. Multiple pharmacologic AGE inhibitory agents are currently under development, but clinical applications are still limited due to safety issues. Thus, it is necessary to identify a safe anti-glycation agent. It is known that burdock roots have antioxidant, anti-inflammatory, and anti-cancer activities. The objective of the present study was to investigate the inhibitory role of burdock roots on the formation of high glucose-induced glycation of bovine serum albumin (BSA). Methods: In this study, glycation of BSA by glucose, galactose, or fructose at $37^{\circ}C$ for 3 weeks was assessed based on levels of ${\alpha}$-dicarbonyl compounds (early-stage glycation products), fructosamine (intermediate products of glycation), and fluorescent AGEs (late-stage glycation products). In order to compare the inhibitory actions of burdock root extract in AGE formation, aminoguanidine (AG), a pharmacological AGE inhibitor, was used as a positive control. Results: BSA glycation by glucose, fructose, and galatose was dose- and time-dependently produced. Burdock root extract at a concentration of 4 mg/mL almost completely inhibited glucose-induced BSA glycation. The results demonstrate that burdock root extract inhibited AGE formation with an $IC_{50}$ value of 1.534 mg/mL, and inhibitory activity was found to be more effective than the standard anti-glycation agent aminoguanidine. This study identified a novel function of burdock root as a potential anti-glycation agent. Conclusion: Our findings suggest that burdock root could be beneficial for preventing diabetic complications.

• Journal of Life Science
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• v.23 no.2
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• pp.157-166
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• 2013

This study aimed to investigate whether nociceptin contributes to the alterations in cerebral blood flow (CBF) regulation following postnatal exposure to ethanol in Sprague-Dawley rats. Animals received ethanol twice a day, 2 hr apart, on postnatal 6, 7 and 8 days. The changes in regional CBF (rCBF) in response to the changes in mean arterial blood pressure were determined at 4-, 8-, and 12-week of age by laser-Doppler flowmetry. Hypotension was induced by the gradual withdrawal of blood from arterial catheter, and the reversal of blood pressure was produced by the reinfusion of blood. Expression of nociceptin-like immunoreactivity was determined in dura mater and cerebral cortex using immunohistochemistry. Postnatal exposure to ethanol almost abolished the autoregulation of rCBF in all age groups. Pretreatment with nociceptin but not with [$Nphe^1$]nociceptin(1-13)$NH_2$, a selective competitive nociceptin receptor antagonist, 5 min prior to ethanol administration preserved the autoregulation of rCBF in all age groups. Postnatal exposure to ethanol markedly increased the expressions of nociceptin-like immunoreactivity in the dura mater and cerebral cortex, both of which were significantly inhibited by pretreatment with 7-nitroindazole monosodium salt as well as aminoguanidine 5 min prior to ethanol administration in all age groups. The values of arterial blood gas analysis were not significantly different from the basal levels in all groups. These results suggest that nociceptin deeply contributes to the compensatory mechanisms for the nitric oxide-dependent alterations in CBF autoregulation following postnatal exposure to ethanol.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.197.2-197.2
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• 2003

One of the consequences of hyperglycemia is the excessive nonenzymatic glycation of proteins known as Millard reaction. Under hyperglycemia the irreversibly formed advanced glycation endproducts(AGEs) do not return to normal when hyperglycemia is corrected and continue to accumulate over the lifetime of protein. AGEs are largely involved in the pathogenesis of diabetic complications. To find possible AGEs inhibitor, BSA was added to a mixture of sugars and unprocessed-, processed Coptidis Rhizoma, Berberine, its standard compound or AG(Aminoguanidine HCl: positive control). (omitted)

• Korean Journal of Pharmacognosy
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• v.40 no.4
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• pp.382-387
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• 2009

Enhanced formation and accumulation of advanced glycation end products (AGEs) have been implicated as a major pathogenesis process leading to diabetic complications, normal aging, atherosclerosis and Alzheimer's disease. In our ongoing project to discover novel treatments for diabetic complications from natural sources, we have investigated on the inhibitory activity of 67 ethanol extracts from 57 Korean herbal medicines against the formation of AGEs in vitro. Of these, 22 extracts were found to have a significant AGEs inhibitory activity ($IC_{50}$<50 ${\mu}g$/ml) compared with aminoguanidine ($IC_{50}$=75.98 ${\mu}g$/ml). Particularly, 6 extracts from 3 herbal medicines, Castanea crenata (flower, leaf, bark-twig), Acer tatarium subsp. ginnala (fruit) and Sapium japonicum (leaf, twig) showed (approximately 8-17 fold) stronger inhibitory activity than that of aminoguanidine.

• IMMUNE NETWORK
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• v.4 no.2
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• pp.108-115
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• 2004

Background: Production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathology of autoimmune disease. It is unknown whether iNOS expression is increased within testes and whether iNOS and NO have essential roles in the pathogenesis of EAO. Methods: EAO was induced in guinea pig testes at 17 days after secondary immunization by administration of crude extract (CE) and purified glycoprotein 1 (GP1) from normal guinea pig testes. iNOS gene expression was assessed by RT-PCR and Northern blot analysis in testes. Localization of iNOS and Mac-1 and the indicator of NO-mediated tissue injury, nitrotyrosine, were detected in the testicular lesion by immunohistochemistry. Results: In control testes, inflammation and iNOS gene expression were not detected, whereas, in CE- and GP1-injected testes, inflammation and marked iNOS gene expression were evident at day 17 after secondary immunization. Immunohistochemistry of Mac-1 showed the colocalization with iNOS protein and nitrotyrosyl proteins in intertubules, suggesting that NO produced by infiltrated macrophages may be involved in inflammatory lesions of intertubules. Intraperitoneal administration of aminoguanidine significantly prevented EAO with reduction of inflammation, iNOS expression and nitrotyrosine formation. Conclusion: These results suggest that NO production by macrophages may be important in the pathogenesis of CE- and GP1-induced EAO. Furthermore, this study demonstrated the therapeutic potential of iNOS inhibitor in the treatment of inflammatory and autoimmune mediated-diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.345-353
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• 1997

The effects of crude saponin (SAP) and alkaloid (ALK) fractions of Panax ginseng C.A. Meyer on the detrimental effects of electroconvulsive shock (ECS) and scopolamine on passive avoidance response (PAR) were studied in male Sprague-Dawley rats, referring their effects on the neuronal injury and plasticity of hippocampus in response to electrolytic lesion of left entorhinal cortex (ECL). The detrimental ECS effect on PAR was attenuated by pre- and post-treatments with SAP and ALK, respectively, or by pretreatment with aminoguanidine (AG), an inhibitor of diamine oxidase and NO synthase. And the detrimental scopolamine effect on PAR was also inhibited by pre-treatment with ALK or AG, and by post- treatment with SAP or ALK, respectively. On the 7th day after ECL, the brain sections stained by cresyl violet and by acetylcholinesterase (AChE) histochemistry, respectively, showed the chromatolysis and numeral decrease of neurons and the reduction of AChE reactivity in the hippocampus CA1 area and to a lesser extent, in the dentate gyrus. The neuronal cell death of the CA1 area was significantly reduced by SAP, ALK, or AG, and the reduction of AChE reactivity was significantly attenuated by SAP or ALK and to a lesser extent by AG. These results suggests that the protective effect of ginseng SAP and ALK fractions on ECS- or scopolamine-induced impairment of PAR may be ascribed in part to preservation of hippocampal neurons, particularly cholinergic neurons.

• Natural Product Sciences
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• v.14 no.3
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• pp.192-195
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• 2008

Three known compounds, puerarol (1), pueroside B (2), and ononin (3), were isolated from an EtOAc-soluble fraction of the roots of Pueraria lobata. The isolates (1 - 3) were subjected to an in vitro bioassay to evaluate their inhibitory activity on the formation of advanced glycation end products (AGEs). Puerarol (1) exhibited a remarkable inhibitory activity on AGEs formation with $IC_{50}$ value of $2.05{\pm}0.32{\mu}M$ as compared with positive control, aminoguanidine ($IC_{50}$ value : $905.32{\pm}7.58{\mu}M$).

• Korean Journal of Pharmacognosy
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• v.37 no.1 s.144
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• pp.48-52
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• 2006

Advanced glycation end products (AGEs) are largely involved in the pathogenesis of diabetic complications. As part of our ongoing project directed toward the discovery of preventive and/or delay agents for diabetic complications from natural sources, 92 Korean traditional herbal medicines have been investigated with an in vitro evaluation system using AGEs inhibitory activity. Of these, 17 herbal medicines exhibited a significant inhibitory activity against AGEs formation. Particularly, 9 herbal medicines, i.e., Cinnamomi Cortex, Artemisiae Argyi Herba, Ammoni Tsao-ko Fructus, Menthae Herba, Amomi Semen, Polygoni Avicularis Herba, Lycopi Herba, Salviae Radix, and Nelumbinis Semen showed more potent inhibitory activity (2-4 fold) than the positive control aminoguanidine.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.407-412
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• 2000

The presence of the nitric oxide synthase (NOS) enzyme from Salmonella typhimurium (S. typhimurium) was identified by measuring radiolabeled L-$[^3H]$citrulline and NO, and Western blot analysis. NOS was partially purified by both Mono Q ion exchange and Superose 12HR size exclusion column chromatography, sequentially. The molecular weight of NOS was estimated to be 93.3 kDa by Western blot analysis. The enzyme showed a significant dependency on the typical NOS cofactors; an apparent Km for L-arginine of 34.7 mM and maximum activity between $37^{\circ}C$ and $43^{\circ}C$. The activity was inhibited by NOS inhibitors such as aminoguanidine and $N^{G}$ $N^{G}$-dimethyl-L-arginine. taken together, partially purified NOS in S. typhimurium is assumed to be a different isoform of mammalian NOSs.OSs.