• 생약학회지
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• 제39권3호
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• pp.249-254
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• 2008

An 80% EtOH extract and the solvent fractions of the seeds of Cornus officinalis were evaluated for their inhibitory activities against advanced glycation end products (AGEs) formation and AGEs-induced protein cross-linking in vitro. In vitro assay for AGEs-bovine serum albumin (BSA) formation showed that the 80% EtOH extract, n-hexane, EtOAc, n-BuOH and water fractions significantly inhibited AGEs formation with observed $IC_{50}$ values of 1.13, 17.64, 1.52, 1.24 and $3.27{\mu}g/ml$, respectively. In indirect AGEs-ELISA assay, the 800% EtOH extract, EtOAc and n-BuOH fractions exhibited more potent inhibitory activity on AGEs-BSA formation than aminoguanidine, a well know AGEs inhibitor. Furthermore, the 80% EtOH extract and all the solvent fractions inhibited concentration-dependently AGE-BSA cross-linking to collagen. The 80% EtOH extract, EtOAc, n-BuOH and water fractions also had a breaking activity against preformed AGE-BSA cross-linking concentration dependently. Thus these results suggest that the 80% EtOH extract and fractions of the seeds of C. officinalis could be an inhibitor as well as breaker of AGE-BSA cross-linking.

• 생약학회지
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• 제43권4호
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• pp.338-344
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• 2012

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, 62 herbal medicines from China and Vietnam have been investigated with an in vitro evaluation system using AGEs formation inhibitory activity. Of these, 5 herbal medicines ($IC_{50}$ < $5{\mu}g/ml$) were found to have significant AGEs formation inhibitory activity. Particularly, herbal medicines Albizia odoratissima (twigs and leaves), Rhododendron spinuliferum (twigs and leaves), Dioscorea cirrhosa (stems and leaves), Illicium verum (stems and leaves) and Aglaia perviridis (stems and leaves), showed more potent inhibitory activity (approximately 16-26 fold) than the positive control aminoguanidine ($IC_{50}=76.47{\mu}g/ml$).

• 대한수의학회지
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• 제44권3호
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• pp.389-397
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• 2004

The therapeutic efficacy of xylamine in the field of psychological medicine has been recognized for years and the drug is used to treat depression and some other conditions, but little is known about its mechanism of action on vascular system. Therefore, the present study was designed to investigate the influence of xylamine on the contractile responses of isolated rat thoracic arteries to phenylephrine(PE) and potassium chloride(KCl). Xylamine produced a concentration-dependent relaxation in PE-precontracted endothelium intact(+E) rat aortic rings, but not in a KCl-precontracted aortic rings. Also, xylamine inhibited the PE-induced contraction in concentration-dependent manner, but not in the high KCl-induced contraction in +E rings. This concentration-dependent inhibition was suppressed by the removal of the endothelium (-E). The inhibitory effects of xylamine($0.3{\mu}M$) on the PE-induced contractions were suppressed by N(G)-nitro-L-arginine(L-NNA), N(omega)-nitro-L-arginine methyl ester(L-NAME), aminoguanidine, dexamethasone, methylene blue, 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one(ODQ), indomethacin, ryanodine, tetrabutylammonium(TBA), lidocaine, procaine and 0 mM extracellular $Na^+$, but not by 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate(NCDC), lithium, nifedipine, verapamil, 0 mM extracellular $Ca^{2+}$, glibenclamide and clotrimazole. These findings suggest that xylamine could act as a vasorelaxant and direct inhibitor of arterial contraction. This vasorelaxation involves an endothelial nitric oxide (NO)/cGMP (guanosine 3',5'-cyclic monophosphate) pathway or cyclooxygenase system, and an interference with $Ca^{2+}$ release, TBA-sensitive $Ca^{2+}$-activated $K^+$ channels and $Na^+$$ channels.

• 한국식생활문화학회지
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• 제37권6호
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• pp.503-509
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• 2022

Methylglyoxal is a highly reactive precursor which forms advanced glycation end products (AGEs). AGEs and methylglyoxal are known to induce various diseases such as diabetes, vascular disorders, Diabetes Mellitus (DM), and neuronal disorders. Juglans regia L is an important food commonly used worldwide, having nutritious components, including phenolic compounds. Since ancient times, Juglans regia L have been differently applied by various countries for health and in diverse diseases, including arthritis, asthma, skin disorders, cancer, and diabetes mellitus. However, the effect of diabetes-induced renal damage against AGEs remains unclear. This study evaluates the anti-glycation and renal protective effects of ethanol extract of Juglans regia L against methylglyoxal-induced renal tubular epithelial cell death. Exposure to methylglyoxal resulted in reduced cell viability in NRK-52E cells, but co-treatment with Juglans regia L extracts significantly increased the cell viability. In addition, we examined the anti-glycation effect of Juglans regia L extracts. Compared to the positive control aminoguanidine and Alagebrium, treatment with Juglans regia L extracts significantly inhibited the formation of AGEs, collagen cross-linking, and breaking collagen cross-linking. Taken together, our results indicate that Juglans regia L is a potential therapeutic agent for regulating diabetic complications by exerting anti-glycation and renal protective activities.

• 대한약리학회지
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• 제30권3호
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• pp.273-289
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• 1994

뇌-허혈후 나타나는 신경세포의 손상에 glutamate의 과다한 유리와 그의 N-methyl-D-aspartate (NMDA) 수용체: calcium 통로 활성작용 및 polyamine중 putrescine의 증가로 인한 신경세포내 $[Ca^{2+}]$의 상승과 관련 있다는 보고들이 있다. 본 연구에서는 Mongolian gerbil에서 5분간 경동맥을 차단하여 뇌-허혈을 가한후 재관류시 해마의 세포외액내 polyamine, glutamate, acetylcholine농도, 해마의 $[^3H]MK-801$ 결합능의 변동 및 해마조직소견의 변동에 미치는 비가역성 ornithine decarboxylase (ODC) 억제제인 difluoromethylornithine (DFMO), diamine oxidase (DAO) 억제제인 aminoguanidine (AG), NMDA 수용체 길항제인 MK-801 및 calcium 통로 차단제인 nimodipine (NM)의 효과를 비교-검색하였다. 해마 세포외액내 polyamine, glutamate 및 acetylcholine은 microdialysis probe를 해마의 CA1부위에 위치시킨 후 나온 분취액을 HPLC와 luminometer를 사용하여 측정하였고, 해마조직에서 신경세포의 손상은 cresyl-violet 염색법으로 관찰하였다. 허혈후 해마 세포외액내 putrescine농도는 5분이내에 급속히 증가하여 뇌-허혈후 96시간까지 증가되는 경향을 보였으며 AG과 MK-801 처치시 saline 처치군에 비하여 증가정도가 상승되었으나 NM과 DFMO 처치로 putrescine의 증가는 감소되는 경향을 보였다. 해마 세포외액내 glutamate의 농도는 허혈후 5분 이내에 9배이상 유의하게 증가한 후 급격히 감소되어 25분후에는 정상치로 회복되었으나, 이같은 변동은 AG, DFMO 및 MK-801 처치로 영향을 받지 않았고 NM 처치로는 glutamate의 증가가 둔화되는 경향을 보였다. 해마 세포외액내 acetylcholine 농도는 허혈에 의하여 큰변동이 없었으나 허혈전 acetylcholine농도는 DFMO나 MK-801처치로 감소되는 경향을 보였다. 해마-synaptosome막의 $[^3H]MK-801$ 결합능은 saline 처치군에 비하여 AG과 MK-801 처치로 유의하게 감소되었다. 해마의 조직소견상 AG과 NM은 허혈후의 신경세포손상을 억제하고, MK-801은 손상의 예방에 별 영향을 주지 못하였으나 DFMO는 허혈에 의한 신경세포의 손상을 더욱 악화시키는 경향을 보였다. 이상의 결과로 미루어 NM과 다른기전으로 AG은 해마신경세포의 손상을 NMDA-수용체: calcium 통로의 활성화를 조절하여 허혈성 뇌손상을 억제할 수 있으리라 사료된다.

• IMMUNE NETWORK
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• 제1권2호
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• pp.116-125
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• 2001

Background: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro- and anti-inflammatory effects in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). Method: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)- or interphotoreceptor retinoid binding protein (IRBP)-immunized rats could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiments, the rats were treated orally with MSDM (10 mg/kg/day) at the early stage (-1~4 days) or throughout the experimental period (-1~15 days). Results: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development. A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP- or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-${\gamma}$. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rats without MSDM secreted high concentrations of IFN-${\gamma}$, but low concentrations of IL-10. Conclusion: In conclusion, NO administation suppresses EAE and EAU by modulating the Th1/Th2 balance during inflammatory immune responses. This work further suggests that NO may be useful in the therapeutic control of autoimmune disease.

• 대한수의학회지
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• 제43권3호
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• pp.361-371
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• 2003

The vasorelaxant actions and blood pressure lowering of the ${\alpha}_2$-adrenoceptor agonists (${\alpha}_2$-AAs) clonidine and xylazine were investigated in rat isolated aortic rings and anesthesized rats. Both clonidine and xylazine produced a concentration-dependent inhibition of the sustained contraction induced by norepinephrine (NE), but not by KCl. NE-induced contractions were attenuated partly by nifedipine or verapamil, voltage dependent $Ca^{2+}$ channel blockers. These $Ca^{2+}$ channel blockers-resistant contractions were abolished by clonidine or xylazine. Inhibitory effects of a ${\alpha}_2$-AAs on contractions could be reversed by ryanodine, an intracellular $Ca^{2+}$, transport blocker, and tetrabutylammonium (TBA), a $Ca^{2+}$ activated $K^+$ channel blocker, but not by nifedipine, glibenclamide or removal of extracellular $Ca^{2+}$ and endothelium. Moreover, ${\alpha}_2$-AAs produced relaxation in NE-precontracted isolated intact aortic rings in a concentration-dependent manner, but not in KCl-precontracted rings. The relaxant effects of ${\alpha}_2$-AAs were inhibited by ryanodine and TBA, but not by nifedipine, glibenclamide, N (G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), 2-nitro-4-carboxyphenyl N,N-diphenylcarhurnte (NCDC), lithium sulfate, staurosporine or removal of extracellular $Ca^{2+}$ and endothelium. In vivo, infusion of xylazine elicited significant decrease in anerial blood pressure. This xylazinelowered blood pressure was completely inhibited by the intravenous injection of TBA, but not by the intravenous injection of glibenclamide, L-NNA, L-NAME, AG, nifedipine, lithium sulfate or saponin.. These findings showed that the receptor-mediated and ${\alpha}_2$-adrenoceptor A-stimulated endothelium-independent vasorelaxant effect may be explained by decreasing intracellular $Ca^{2+}$ release and activation of $Ca^{2+}$-activated $K^+$ channels, which may contribute to the hypotensive effects of ${\alpha}_2$-AAs in rats.

• Journal of Yeungnam Medical Science
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• 제13권2호
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• pp.159-172
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• 1996

대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.

• 대한화장품학회지
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• 제43권3호
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• pp.239-245
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• 2017

노화는 생리학적으로 비가역적으로 일어나는 과정으로 노화가 진행됨에 따라 단백질의 산화화학반응 등으로 노화징후가 축적된다. 활성산소와 당화된 최종 당화산물(advanced glycation endproducts, AGEs 최종 당화산물)은 생체 조직과 세포를 공격하여 노화를 촉진한다고 알려져 있다. 본 연구에서는 항산화 물질로 알려진 aminoguanidine을 양성 대조군으로 anti-glycation 효과를 확인하였으며, methoxy PEG-45 thioctate(LA-PEG)를 농도별로 처리하여 anti-glycation 효과를 평가하였다. 실험결과 LA-PEG는 매우 우수한 anti-glycation 효과로 최종 당화산물(AGEs) 생성억제 활성이 매우 우수하게 나타났으며, 항산화 효과와 밀접한 연관을 나타냈다. 또, 세포노화 지표물질인 senescence-associated ${\beta}$-galactosidase ($SA-{\beta}-gal$) 활성을 사람 섬유아세포(HDF)를 이용하여 확인한 결과, LA-PEG를 처리하였을 때 염색된 세포의 수가 감소하여 세포의 senescence를 억제하는 것을 확인할 수 있었다. 본 연구결과, LA-PEG의 anti-glycation 효과 및 산화로 인한 단백질 손상에 대한 보호 효과가 우수하게 나타났으며, 항노화 화장품에 적용 시 효과적으로 적용할 수 있을 것으로 사료된다.

• 동의생리병리학회지
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• 제31권5호
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• pp.264-269
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• 2017

Prunella vulgaris, well-known traditional medicinal plant, is used for the cure of abscess, scrofula, hypertension and urinary diseases. Diabetic nephropathy is the most common cause of end-stage renal disease. The pathological characteristics of diabetic nephropathy are glomerular and tubular basement membrane thickening. The aim of the present study was to evaluate the effect of Prunella vulgaris, on diabetic glomerular injury in streptozotocin-induced diabetes rats. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ; 45 mg/kg) and confirmed by random glucose level higher than ${\leq}300mg/dL$. The experimental rats were divided into five groups: control group (Male SD rats), STZ group (Male SD rats injected STZ), Aminoguanidine group (Male SD rats injected STZ + AG 100 mg/kg/day), Low dose group (Male SD rats injected STZ + APV 100 mg/kg/day), High dose group (Male SD rats injected STZ + APV 300 mg/kg/day). AG or APVs were administered once a day for 8 weeks. Body weight and food/water intake were measured every four weeks. At the end of study, the kidneys were collected and cut into pieces for immunohistochemistry and western blot analysis. Our study showed that body weight and water/food intake were no significant differences between untreated STZ-induced diabetic rat and APV treated-STZ rat. However, phosphorylation of receptor-regulated Smads (Smad3) was significantly decreased in APV treated-STZ rat as compared with the diabetic group. In addition, APV was improved nephrin level in kidney tissue. Therefore, we suggest that APV has a protective effect against STZ-induced diabetic glomerular injury.