• 생약학회지
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• 제42권2호
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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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• 제49권4호
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• pp.233-240
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• 2016

항산화, 항암 및 항염증 효능 등의 생리 활성이 보고된 우엉 뿌리의 열수 추출물을 제조하여 advanced glycation end products (AGEs) 형성 저해 효과를 확인하였다. AGEs는 bovine serum albumin (BSA)과 단당류인 glucose, fructose, galactose를 혼합하여 $37^{\circ}C$에서 3주간 배양하여 생성하였고 매주 형광도 측정, fructosamine 분석, ${\alpha}$-dicarbonyl compounds 함량 분석을 통해 AGEs의 생성량을 확인하였다. 우엉 뿌리 추출물의 AGEs 생성 저해능을 AGEs 생성 억제제로 알려져 있는 aminoguanidine (AG)의 저해능과 비교하였다. 우엉 뿌리 추출물은 BSA와 단당류인 glucose, fructose, galactose 각각의 당화반응을 억제하였으며 특히 배양 3주차에서 BSA와 glucose의 당화반응 결과물인 AGEs 생성을 유의적으로 저해하였다. 농도 2 mg/mL 이상의 우엉 뿌리 추출물은 1 mM AG보다 AGEs 생성 저해능이 우수하였으며 농도 4 mg/mL의 우엉 뿌리 추출물은 배양 3주차에서 AGEs 생성을 약 80% 이상 억제하는 효능을 나타냈다. 체내 혈당은 당뇨병과 같은 질환과 식이의 영향을 받으므로 다양한 glucose 농도에서 우엉 뿌리 추출물의 AGEs 생성 억제능을 조사하였다. 그 결과 AGEs 생성은 glucose의 농도에 비례하여 증가하였으며 우엉 뿌리 추출물은 당뇨환자의 식후에 관찰되는 혈당인 25 mM glucose 군에서 1 mM의 AG보다 높은 우수한 저해 효과를 확인하였다. 본 연구 결과는 우엉 뿌리 추출물의 AGEs 생성 억제라는 새로운 기능성을 밝히며 향후 당뇨 합병증 예방 효능을 가진 기능성 식품으로의 개발 가능성을 제시한다.

• 생명과학회지
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• 제23권2호
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• pp.157-166
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• 2013

본 연구는 Sprague-Dawley계 숫쥐에서 출생 초기 에탄올에의 노출에 의한 성장 후 뇌혈류 자가조절의 변동을 관찰하고 이러한 변동에 대한 nociceptin의 관여를 관찰하고자 하였다. 실험동물에게 에탄올 2.5 g/kg을 생후 6, 7 및 8일의 3일 동안 2시간 간격으로 1일 2회 피하 주사하였다. 주령 4, 8 및 12주 시기에 단계적 출혈에 의한 저혈압 및 혈액 재주입에 의한 혈압 상승시의 평균동맥혈압의 변동에 따른 국소 뇌혈류 변동을 laser-Doppler flowmetry 방법으로 측정하였고, 경막과 대뇌피질에서 nociceptin-유사 면역반응력의 발현을 면역조직화학법으로 측정하였다. 출생 초기 에탄올 투여는 4, 8 및 12주령 모두에서 국소 뇌혈류 자가조절 기능을 거의 소실시켰다. 에탄올 투여 전에 nociceptin을 전처치한 군에서는 모든 연령군에서 국소 뇌혈류 자가조절 기능이 보존되었으나, nociceptin 수용체 선택적 경쟁적 길항제인 [$Nphe^1$]nociceptin(1-13)$NH_2$를 전처치한 군에서는 보존되지 아니하였다. 출생 초기 에탄올 투여에 의하여 경막 내 nociceptin-유사 면역반응력이 모든 연령군에서 현저히 증가하였고, 7-nitroindazole (7-NINA) 전처치뿐만 아니라 aminoguanidine 전처치에 의하여 모든 주령에서 유의하게 억제되었다. 출생 초기 에탄올 투여에 의하여 대뇌피질 내 nociceptin-유사 면역반응력이 모든 연령군에서 현저히 증가하였고, 7-NINA 전처치와 aminoguanidine 전처치에 의하여 모든 주령에서 유의하게 억제되었다. 모든 실험군의 동맥혈가스분석 결과는 실험 전, 중 및 후에 유의한 차이를 보이지 아니하였다. 이상의 결과로 보아 출생 초기 에탄올 투여는 성장 후 뇌혈류 자가조절에 변동을 초래하고, 이에 대한 보상기전으로서 nociceptin의 발현이 증가하는데, 여기에는 nitric oxide가 깊이 관여하는 것으로 생각된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• 생약학회지
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• 제40권4호
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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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• 제4권2호
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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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• 제1권4호
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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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• 제14권3호
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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 : $905.32{\pm}7.58{\mu}M$).

• 생약학회지
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• 제37권1호통권144호
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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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• 제23권4호
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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.