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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 연구보고서
- 저자정보
- 발행연도
- 2006.12
- 수록면
- 1 - 7 (157page)
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About 120 extracts of herbal medicines were tested for the inhibitory effect on advanced glycation end productions (AGEs) formation and aldose reductase (AR) in vitro as an our preliminary study. Of these, 84 herbal medicines and single compounds showed a potent inhibitory action on AGEs formation, and 21 herbal medicines and single compounds were proved to be a good in vitro AR inhibitor.
Based on above preliminary screening data, a multi-herbal medicine, KIOM-79, CS, KIOM-80, and a pure compound, KIOM-10 and compound K4, were chosen for more detailed investigation with type Ⅰ and type Ⅱ animal models. In the first place, in diabetes group treated with CS in streptozotocin (STZ)-induced rats, CCr and proteinuria were significantly decreased. CCr and proteinuria are important factors for kidney function. Also, other related factors including expression of TGF -βl, PKC, VEGF, eNOS, ECM, type Ⅲ collagen in kidney were significantly changed. Immunohistochemical staining showed CS prevented glomeruli enlargement and also density of AGEs, RAGE, TGF-β1 and type Ⅳ collagen.
KIOM-79 with low concentration was administrated to type 1 animal model. CCr was significantly decreased and proteinuria showed a tendency to be decreased. It inhibited significantly expression of Fibronectin, PKC and VEGF mRNNprotein. Immunohistochemical staining showed KIOM-79 prevented glomeruli enlargement and also density of AGEs and type IV collagen.
Taking together all data, CS and KIOM-79 showed a great potential for prevention of the prog TGF-β1, VEGF and fibronectin expression by high glucose (25 mM) or Sl00b (5 ㎍/㎖) was prevented by KIOM-10 in a dose dependent manner in human retinal pigment epithelial (RPE) cells. Also, KIOM-10 inhibited extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)/Akt activation and lipid peroxidation (the formed malondialdehyde (MDA) levels) in human RPE cells. The present study demonstrates high glucose- or S100b- induced VEGF, TGF-βI and fibronectin expression and KIOM-10 inhibits high glucose- or S100b-induced TGF -β1 expression and secretion and fibronectin expression via ERKIMAPKI Akt signaling pathway in human RPE cells.
In human lens epithelial cells, PO41-14-42-Kl inhibited expression of TGF-β2 mRNA and protein. Ex vivo study, treatment of PO41-14-42-Kl decreased the opacity of lens by 22%.
For mechanism investigation of diabetic nephropathy, we established the mesangial cell culture from rats kidney.
The expression of VEGF and AGEs were significantly increased in retina of streptozotocine (STZ)-induced diabetic rats. Moreover, VEGF and AGEs levels are markedly increased in serum of diabetic rats compared with normal rats. However, there is no significant correlation of VEGF and AGEs in serum of diabetic rats.
As part of research for isolation of novel, natural inhibitors on AGEs formation from herbal medicines, a new compounds, Puerariafuran, as well as 32 known compounds were isolated from several herbal medicines, using an in vitro bioassay based on the inhibition of AGEs to monitor chromatographic fractionation. Puerariafuran exhibited about nine hundred times stronger inhibitory activity on AGEs formation than aminoguanidine used as the positive control in this study.
Based on above preliminary screening data, a multi-herbal medicine, KIOM-79, CS, KIOM-80, and a pure compound, KIOM-10 and compound K4, were chosen for more detailed investigation with type Ⅰ and type Ⅱ animal models. In the first place, in diabetes group treated with CS in streptozotocin (STZ)-induced rats, CCr and proteinuria were significantly decreased. CCr and proteinuria are important factors for kidney function. Also, other related factors including expression of TGF -βl, PKC, VEGF, eNOS, ECM, type Ⅲ collagen in kidney were significantly changed. Immunohistochemical staining showed CS prevented glomeruli enlargement and also density of AGEs, RAGE, TGF-β1 and type Ⅳ collagen.
KIOM-79 with low concentration was administrated to type 1 animal model. CCr was significantly decreased and proteinuria showed a tendency to be decreased. It inhibited significantly expression of Fibronectin, PKC and VEGF mRNNprotein. Immunohistochemical staining showed KIOM-79 prevented glomeruli enlargement and also density of AGEs and type IV collagen.
Taking together all data, CS and KIOM-79 showed a great potential for prevention of the prog TGF-β1, VEGF and fibronectin expression by high glucose (25 mM) or Sl00b (5 ㎍/㎖) was prevented by KIOM-10 in a dose dependent manner in human retinal pigment epithelial (RPE) cells. Also, KIOM-10 inhibited extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)/Akt activation and lipid peroxidation (the formed malondialdehyde (MDA) levels) in human RPE cells. The present study demonstrates high glucose- or S100b- induced VEGF, TGF-βI and fibronectin expression and KIOM-10 inhibits high glucose- or S100b-induced TGF -β1 expression and secretion and fibronectin expression via ERKIMAPKI Akt signaling pathway in human RPE cells.
In human lens epithelial cells, PO41-14-42-Kl inhibited expression of TGF-β2 mRNA and protein. Ex vivo study, treatment of PO41-14-42-Kl decreased the opacity of lens by 22%.
For mechanism investigation of diabetic nephropathy, we established the mesangial cell culture from rats kidney.
The expression of VEGF and AGEs were significantly increased in retina of streptozotocine (STZ)-induced diabetic rats. Moreover, VEGF and AGEs levels are markedly increased in serum of diabetic rats compared with normal rats. However, there is no significant correlation of VEGF and AGEs in serum of diabetic rats.
As part of research for isolation of novel, natural inhibitors on AGEs formation from herbal medicines, a new compounds, Puerariafuran, as well as 32 known compounds were isolated from several herbal medicines, using an in vitro bioassay based on the inhibition of AGEs to monitor chromatographic fractionation. Puerariafuran exhibited about nine hundred times stronger inhibitory activity on AGEs formation than aminoguanidine used as the positive control in this study.
목차
[요약문]
SUMMARY
제1장 연구 개발과제의 개요
제2장 국내외 기술개발 현황
제3장 연구개발 수행내용 및 결과
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UCI(KEPA) : I410-ECN-0101-2009-519-016568262