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ABSTRACT: KIOM-79 is a mixture of 80% ethanol extracts of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix. The preventive effect of KIOM-79 on the development of diabetic keratopathy has been investigated.
Seven-week-old male Zucker diabetic fatty (ZDF) rats were treated with KIOM-79 (50 mg/kg body weight) once a day orally for 13 weeks. The thickness of the cornea was measured and the extent of corneal cell death was detected by a terminal deoxynucleotidyl transferase dUTP nick-end labelling assay. The expression of advanced glycation end products (AGEs), 8-hydroxydeoxyguanosine, nuclear factor-kappaB (NF-κB), Bax and Bcl-2 were evaluated in corneal tissues.
The administration of KIOM-79 prevented corneal oedema and apoptotic cell death of corneal cells. The accumulation of AGE in corneal tissues was reduced in ZDF rats treated with KIOM-79. Moreover, KIOM-79 attenuated oxidative DNA damage, NF-κB activation and Bax overexpression in the cornea.
The results suggested that KIOM-79 exhibited corneal protective properties by not only reducing oxidative stress but inhibiting the AGEs/NF-κB downstream signal pathway during the development of diabetic keratopathy.
The Journal of pharmacy and pharmacology. 04/2011; 63(4):524-30.
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ABSTRACT: Advanced glycation end products (AGEs) play an important role in the development of chronic diabetic complications. Chlorogenic acid (CGA) is a phenolic compound formed by the esterification of caffeic and quinic acids. In this study, we evaluated the inhibitory effects of CGA against the formation of AGEs and AGEs protein cross-linking in vitro. An in vitro assay for glycation of bovine serum albumin by high glucose showed that CGA inhibited AGEs formation with an IC(50) value of 148.32 μM and was found to be more effective than aminoguanidine, a well-known AGEs inhibitor (IC(50); 807.67 μM). In an indirect AGE-ELISA assay, the CGA exhibited more potent inhibitory activity on the cross-linking of AGEs to collagen than aminoguanidine. In addition, the inhibitory effects of CGA on AGEs formation and on its cross-linking with collagen might be caused by its interactions with reactive decarbonyl compounds, such as methylglyoxal. These results suggest that CGA could be beneficial in the prevention of AGEs progression in patients with diabetes because CGA can attenuate AGEs deposition in glucose.
Archives of Pharmacal Research 03/2011; 34(3):495-500. · 1.59 Impact Factor
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ABSTRACT: Previous studies have reported that KIOM-79 shows a strong inhibitory effect on AGE formation and inhibited a proinflammatory state in a murine macrophage cell line. In the present study, we investigated the effect of KIOM-79 on AGE accumulation and vascular inflammation in the aorta of Zucker diabetic fatty (ZDF) rats, a commonly used model of type 2 diabetes. Seven-week-old male ZDF rats were treated with KIOM-79 (50 mg/kg) once a day orally for 13 weeks. We examined the dissected aortas for AGE accumulation, expression of the receptor for AGEs (RAGE), and the expression of proinflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and vascular adhesion molecule-1 (VCAM-1). Nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were also measured by Southwestern histochemistry, electrophoretic mobility shift assay (EMSA), and immunohistochemistry, respectively. KIOM-79 markedly reduced the accumulation of AGEs and the expression of RAGE in the aorta. We also found that KIOM-79 attenuated the expression of inflammatory factors including NF-κB, MCP-1, VEGF, VCAM-1, and iNOS in the aortas of ZDF rats. These data suggest that KIOM-79 may prevent or retard the development of inflammation in diabetic vascular disease.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011:784136. · 4.77 Impact Factor
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ABSTRACT: Damage of lens epithelial cells (LECs) has been implicated in cataract formation. The aim of this study was to investigate the protective effect of KIOM-79, a combination of four plant extracts, on LECs. We examined the levels of advanced glycation end products (AGEs), nuclear factor-kappaB (NF-κB) activation and inducible nitric oxide synthase (iNOS) expression in LECs during cataract development using the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. KIOM-79 was orally administered by gavage to ZDF rats once a day for 13 weeks. Apoptosis was detected by TUNEL assay, and NF-κB activation and iNOS expression were studied by southwestern histochemistry and immunohistochemistry, respectively. In diabetic cataractous lenses, TUNEL-positive LECs were markedly increased 20-fold, and AGEs were highly accumulated (2.7-fold) in LECs. In addition, both NF-κB activation, and iNOS expression were significantly enhanced 3- to 5-fold, respectively, compared to levels found in normal ZL rats. However, the administration of KIOM-79 delayed the development of diabetic cataracts and prevented LEC apoptosis (70%) through the inhibition of AGEs, NF-κB-activation and iNOS expression. These observations suggest that KIOM-79 is useful in inhibiting diabetic cataractogenesis and acts through an antiapoptotic mechanism to protect LECs from injury.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011. · 4.77 Impact Factor
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ABSTRACT: The purpose of the experiment reported here was to assess the involvement of advanced glycation end products (AGEs), oxidative stress, and nuclear factor kappa-B (NF-κB) activation in the development of diabetic keratopathy.
Diabetes was induced by intraperitoneal streptozotocin injection in male Sprague-Dawley rats. The thickness of the cornea was measured. Apoptosis was detected by TUNEL assay and western blot for caspase-3. The expression of AGEs and 8-hydroxydeoxyguanosine (8-OHdG) were studied by immunohistochemistry in corneal tissues of normoglycaemic and diabetic rats. NF-κB activation was evaluated by electrophoretic mobility shift assay and southwestern histochemistry.
Corneal edema was observed in diabetic rats. The thickness of cornea was higher in diabetic than in control rats. AGEs were accumulated in corneal tissues. 8-OHdG and NF-κB were identified in corneal epithelium, stroma and endothelium, and its expressions were greater in diabetic than in those of control rats. Diabetes induces significant alterations in rat corneal tissue structure.
The higher expression of AGE, 8-OHdG and NF-κB in corneal tissues of diabetic rats suggests that these factors are involved in apoptosis and in subsequent corneal alterations related to diabetic keratopathy.
Albrecht von Graæes Archiv für Ophthalmologie 11/2010; 249(4):529-36. · 2.17 Impact Factor
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ABSTRACT: In an ongoing project directed toward the discovery of novel treatments for diabetic complications from traditional herbal medicines, fifteen compounds, apigenin (1), apigenin-7-O-beta-D: -glucopyranoside (2), apigenin-7-O-(6''-O-acetyl)-beta-D: -glucopyranoside (3), luteolin (4), luteolin-7-O-beta-D: -glucopyranoside (5), luteolin-7-O-(6''-O-acetyl)-beta-D: -glucopyranoside (6), isorhamnetin-3-Oneohesperidoside (7), 4-O-caffeoylquinic acid (8), chlorogenic acid methyl ester (9), 4-O-beta-D: -glucopyranosylcaffeic acid (10), lobetyolin (11), cordifolioidyne C (12), isomultiflorenyl acetate (13), beta-sitosterol glucoside (14), and alpha-spinosterol (15), were isolated from an EtOAc-soluble fraction of the flowers of Platycodon grandiflorum (balloonflower; Campanulaceae). The structures of the compounds were identified by physical and spectroscopic methods, as well as by comparison of their data with literature values. All the isolates were evaluated in vitro for inhibitory activity on the formation of advanced glycation end products and rat lens aldose reductase.
Archives of Pharmacal Research 06/2010; 33(6):875-80. · 1.59 Impact Factor
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ABSTRACT: It has been suggested that damage of lens epithelial cell (LEC) may play an important role in cataract formation. Nitric oxide is involved in cataract development. Here, we investigated the relationship between LEC damage and iNOS expression in the Zucker diabetic fatty (ZDF) rat.
At 21 weeks of age, the eyes were enucleated and the lens opacity was then examined. Apoptosis were detected by TUNEL assay, and the expression of iNOS and NF-kappaB activation were studied by immunohistochemistry and southwestern histochemistry respectively.
In 21-week-old male ZDF rats, cataract was developed, TUNEL-positive LECs were markedly increased, and the expression levels of iNOS mRNA and protein were significantly upregulated. The expression pattern of iNOS was closely correlated with apoptotic change of LECs. In addition, advanced glycation end products (AGEs) were accumulated in cytoplasm of LECs. Activated NF-kappaB was mainly detected in nucleus of LECs.
The higher expressions of AGEs, NF-kappaB and iNOS in LECs of diabetic rats suggest that these factors are involved in apoptosis of LEC alterations related to diabetic cataract.
Albrecht von Graæes Archiv für Ophthalmologie 02/2010; 248(6):811-8. · 2.17 Impact Factor
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ABSTRACT: Eight known compounds, lucidin (1), lucidin-omega-methyl ether (2), rubiadin (3), damnacanthol (4), 1,3,6-trihydroxy-2-methoxymethylanthraquinone (5), 3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (6), 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone 3-O-beta-primeveroside (7), and vanillic acid (8), were isolated from EtOAc- and n-BuOH-soluble fractions of the roots of Knoxia valerianoides. The structures of 1-8 were identified by analysis of spectroscopic data as well as by comparison with published values. All the isolates were subjected to in vitro bioassays to evaluate advanced glycation end products (AGEs) formation and rat lens aldose reductase (RLAR) inhibitory activity. Compound 5 showed the most potent inhibitory activity (IC(50) = 52.72 microM) against AGEs formation. Compounds 1, 2, and 8 also showed potent inhibitory activity on AGEs formation with IC(50) values of 79.28, 62.79, and 93.93 microM, respectively, compared with positive control, aminoguanidine (IC(50) = 962 microM). While, compounds 1 and 5-7 showed strong inhibitory activity against RLAR with IC(50) values of 3.35, 3.04, 6.39, and 2.05 microM, respectively.
Archives of Pharmacal Research 02/2010; 33(2):209-14. · 1.59 Impact Factor
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ABSTRACT: Advanced glycation end products (AGEs) have been implicated in the development of diabetic complications, including diabetic nephropathy. KIOM-79, an 80% ethanolic extract obtained from parched Puerariae Radix, gingered Magnolia Cortex, Glycyrrhiza Radix and Euphorbia Radix, was investigated for its effects on the development of renal disease in Zucker diabetic fatty rats, an animal model of type 2 diabetes. In vitro inhibitory effect of KIOM-79 on AGEs cross-linking was examined by enzyme-linked immunosorbent assay (ELISA). KIOM-79 (50 mg/kg/day) was given to Zucker diabetic fatty rats for 13 weeks. Body and kidney weight, blood glucose, glycated hemoglobin, urinary albumin and creatinine excretions were monitored. Kidney histopathology, collagen accumulation, fibrinogen and transforming growth factor-beta 1 (TGF-β1) expression were also examined. KIOM-79 reduced blood glucose, kidney weight, histologic renal damage and albuminuria in Zucker diabetic fatty rats. KIOM-79 prevented glomerulosclerosis, tubular degeneration, collagen deposition and podocyte apoptosis. In the renal cortex, TGF-β1, fibronectin mRNA and protein were significantly reduced by KIOM-79 treatment. KIOM-79 reduces AGEs accumulation in vivo, AGE-protein cross-linking and protein oxidation. KIOM-79 could be beneficial in preventing the progression of diabetic glomerularsclerosis in type 2 diabetic rats by attenuating AGEs deposition in the glomeruli.
Evidence-based Complementary and Alternative Medicine 08/2009; 2011:761859. · 4.77 Impact Factor
