[Show abstract][Hide abstract] ABSTRACT: Ocular pathologic angiogenesis is an important causative risk factor of blindness in retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular macular degeneration. Guibi-tang (GBT) is a frequently used oriental herbal formula in East Asian countries, and is also called Qui-pi-tang in Chinese and Kihi-To in Japanese. In the present study, we investigated the preventive effect of GBT on retinal pathogenic neovascularization in a mouse model of oxygen-induced retinopathy (OIR). C57BL/6 mice were exposed to 75% hyperoxia for five days on postnatal day 7 (P7). The mice were then exposed to room air from P12 to P17 to induce ischemic proliferative retinopathy. GBT (50 or 100 mg/kg/day) was intraperitoneally administered daily for five days (from P12 to P16). On P17, Retinal neovascularization was measured on P17, and the expression levels of 55 angiogenesis-related factors were analyzed using protein arrays. GBT significantly decreased retinal pathogenic angiogenesis in OIR mice, and protein arrays revealed that GBT decreased PAI-1 protein expression levels. Quantitative real-time PCR revealed that GBT reduced vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and plasminogen activator inhibitor 1 (PAI-1) mRNA levels in OIR mice. GBT promotes potent inhibitory activity for retinal neovascularization by decreasing VEGF, FGF2, and PAI-1 levels.
Preview · Article · Dec 2015 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: Retinal neovascularization is a common cause of vision loss in proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. Samul-tang (SMT) is a widely used traditional herbal medicine in East Asia and is also known as Shimotsu-to in Japanese and Si-Wu decoction in Chinese. This study was designed to evaluate the inhibitory effect of SMT on retinal pathogenic angiogenesis in a mouse model of oxygen-induced retinopathy (OIR).
The mice were exposed to a 75 % concentration of oxygen for five days, starting on postnatal day 7 (P7-P12). The mice were then exposed to room air and were intraperitoneally injected with SMT (10 mg/kg or 50 mg/kg) once per day for five days (P12-P16). On P17, we measured retinal neovascularization and evaluated both the expression of angiogenesis-related proteins and changes in the gene expression level in the mRNA.
SMT reduced the area of the central retina and reduced retinal neovascularization in OIR mice. The protein array revealed that SMT reduced the level of SDF-1 protein expression. Quantitative real-time PCR revealed that the HIF-1α, SDF-1, CXCR4 and VEGF mRNA levels in the retinas of OIR mice were elevated compared with those of normal control mice. However, SMT decreased the levels of HIF-1α, SDF-1, CXCR4 and VEGF mRNA in OIR mice.
We are the first to elucidate that SMT inhibits the retinal pathogenic angiogenesis induced by ischemic retinopathy in OIR mice. SMT significantly inhibited retinal neovascularization by downregulating HIF-1α, SDF-1, CXCR4 and VEGF. Based on the results of our study, SMT could be a useful herbal medicine for treating ischemic retinopathy.
Preview · Article · Dec 2015 · BMC Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: In the pathophysiology of diabetic retinopathy (DR), advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF) are thought to have important roles. It is known that VEGF causes a breakdown of the blood‑retinal barrier (BRB) and retinal neovascularization; however, how AGEs affect the retina has largely remained elusive. OSSC1E‑K19 is a novel phytochemical component of Osteomeles schwerinae. The objective of the present study was to evaluate the protective effects of OSSC1E‑K19 on retinal vascular injury in AGE‑modified rat serum albumin (AGE-RSA)-induced retinopathy. AGE-RSA-injected rat eyes were used investigate the protective effects of OSSC1E‑K19 on BRB breakdown. Intravitreal injection of OSSC1E-K19 prevented AGE-RSA-induced BRB breakdown and decreased retinal VEGF expression in retinal vessels. In addition, OSSC1E-K19 inhibited the loss of occludin, a significant tight junction protein. These results supported the potential therapeutic utility of OSSC1E-K19 for retinal vascular permeability diseases.
Preview · Article · Oct 2015 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)‑induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ‑induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ‑induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase‑3, methylglyoxal (MGO) and 8‑hydroxydeoxyguanosine (8‑OHdG) expression levels were measured. STZ‑induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase‑3, MGO and 8‑OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ‑induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase‑3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO‑derived advanced glycation end‑product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ‑induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase‑3 expression, and by restoring the balance of oxidative stress and MGO expression.
Preview · Article · Aug 2015 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: The retinal accumulation of advanced glycation end products (AGEs) is a condition, which is found in diabetic retinopathy. The purpose of the present study was to investigate the protective effect of Litsea japonica extract (LJE) and to elucidate its underlying protective mechanism in model diabetic db/db mice. Male, 7 ‑week‑old db/db mice were treated with LJE (100 or 250 mg/kg body weight) once a day orally for 12 weeks. The expression levels of AGEs and their receptor (RAGE) were subsequently assessed by immunohistochemistry. An electrophoretic mobility shift assay and southwestern histochemistry were used to detect activated nuclear factor κB (NF‑κB). The immunohistochemical analysis demonstrated that LJE significantly reduced the expression levels of the AGEs and RAGE in the neural retinas of the db/db mice. LJE markedly inhibited the apoptosis of retinal ganglion cells. In addition, LJE suppressed the activation of NF‑κB. These results suggested that LJE may be beneficial for the treatment of diabetes‑induced retinal neurodegeneration, and the ability of LJE to attenuate retinal ganglion cell loss may be mediated by inhibition of the accumulation of AGEs.
Preview · Article · Mar 2015 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway. AR-dependent synthesis of excess polyols leads to lens opacification in diabetic cataract. The purpose of this study is to investigate the protective effect of Litsea japonica extract (LJE) on diabetes-induced lens opacification and its protective mechanism in db/db mice. Seven-week-old male db/db mice were treated with LJE (100 and 250 mg/kg body weight) once a day orally for 12 weeks. LJE dose dependently inhibited rat lens aldose reductase activity in vitro (IC50 = 13.53 ± 0.74 µg/mL). In db/db mice, lens was slightly opacified, and lens fiber cells were swollen and ruptured. In addition, lenticular sorbitol accumulation was increased in db/db mice. However, the administration of LJE inhibited these lenticular sorbitol accumulation and lens architectural changes in db/db mice. Our results suggest that LJE might be beneficial for the treatment of diabetes-induced lens opacification. The ability of LJE to suppress lenticular sorbitol accumulation may be mediated by the inhibition of AR activity.
Preview · Article · Feb 2015 · Evidence-based Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: Abstract Many dietary supplements have been sold through advertising their large number of beneficial effects. The aim of this study was to determine whether bilberries (Vaccinium myrtillus) help to prevent diabetes-induced retinal vascular dysfunction in vivo. V. myrtillus extract (VME; 100 mg/kg) was orally administered to streptozotocin-induced diabetic rats for 6 weeks. All diabetic rats exhibited hyperglycemia, and VME did not affect the blood glucose levels and body weight during the experiments. In the fluorescein-dextran angiography, the fluorescein leakage was significantly reduced in diabetic rats treated with VME. VME treatment also decreased markers of diabetic retinopathy, such as retinal vascular endothelial growth factor (VEGF) expression and degradation of zonula occludens-1, occludin and claudin-5 in diabetic rats. In conclusion, VME may prevent or delay the onset of early diabetic retinopathy. These findings have important implications for prevention of diabetic retinopathy using a dietary bilberry supplement.
No preview · Article · Jan 2015 · International Journal of Food Sciences and Nutrition
[Show abstract][Hide abstract] ABSTRACT: Platelet-derived growth factor-BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy. The aim of this study was to evaluate the protective effects of root of Polygonum cuspidatum extract (PCE) on early renal glomerular proliferation in streptozotocin (STZ)-induced diabetic rats.
PCE (100, 350 mg/kg/day) was administered to diabetic rats for 16 weeks. Blood glucose and albuminuria were measured. Renal histology, alpha-smooth muscle actin (alpha-SMA), and proliferating cell nuclear antigen (PCNA) expression levels were also examined.
After 16 weeks of treatment with PCE, severe hyperglycemia and albuminuria were observed in the diabetic rats. The expressions levels of alpha-SMA and PCNA proteins were significantly increased in the glomeruli of the diabetic rats. The expression levels of PDGF-BB and its receptor expressions were greatly increased in the glomeruli of the diabetic rats. However, PCE markedly reduced albuminuria in the diabetic rats. PCE inhibited alpha-SMA and PCNA up-regulation and ameliorated PDGF-BB and PEGFR-Ss protein expression in the diabetic rats. In addition, the binding of PDGF-BB/PDGFR-Ss was inhibited by PCE as shown by an in vitro assay.
These results suggest that PCE has an inhibitory effect on mesangial proliferation in diabetic renal tissues via the inhibition of the interaction of PDGF-BB with its receptor. PCE may have beneficial effects in preventing the progression of diabetic nephropathy.
Preview · Article · Dec 2014 · BMC Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr−/−) mice. In three-week-old male Vldlr−/− mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr−/− mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC50 = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.
No preview · Article · Nov 2014 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: Retinal neovascularization is a common pathology in age-related macular degeneration, retinopathy of prematurity and proliferative diabetic retinopathy. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. Oxygen-induced retinopathy in the mouse is the standard experimental model of proliferative retinopathies. Sipjeondaebo-tang (SDT) is the most widely used traditional herbal formula in East Asia, also known as Shi-Quan-Da-Bu-Tang in Chinese and Juzen-taiho-to in Japanese. SDT has been known to exert anti-angiogenic activities in several tumor models, but the role of SDT in proliferative retinopathies remains unclear. Thus, the object of the present study is to examine the mechanism of action and efficacy of SDT on retinal neovascularization in oxygen-induced ischemic retinopathy (OIR) mice. Neonatal mice at postnatal day 7 (P7) were exposed to 75% concentration of oxygen for 5 days (P7-P12), and then returned to room air from P12 to P17 to induce retinal neovascularization. SDT were administered once per day for 5 consecutive days (P12-P16) by intraperitoneal injection. Retinal neovascularization was measured at P17. We used a protein array to evaluate the expression levels of angiogenic factors. Inhibitory activity of SDT on PDGF-BB/PDGFRβ interaction was evaluated in vitro. Retinal neovascularization in the OIR mice was significantly decreased by SDT. SDT decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, SDT dose-dependently inhibited PDGF-BB/PDGFRβ interaction (IC50 = 388.82 ± 7.31 µg/ml). In conclusion, SDT is a potent inhibitor of retinal neovascularization through inhibiting the pro-angiogenic effect of PDGF-BB.
No preview · Article · Nov 2014 · The Tohoku Journal of Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Background: A number of studies have reported the relationship between environmental temperature and the incidence of myocardial infarction (MI) according to gender, age, and location. The incidence of temperature-associated episodes of MI may increase with aggravated climate conditions, especially in older people, patients with underlying cardiovascular diseases, and those who are poor, uneducated, or isolated. However, scientific evidence is still insufficient especially regarding the risk of low socio-economic status population for temperature-associated MI admissions.
Objectives: In the present study, we evaluated hospital admissions for temperature-associated MI according to gender, age (<75 or ≥75 years), insurance type (National health Insurance (NHI) for the general population, or medical care (Medicaid) for the poor), and location (urban or rural) to compare the risks among these subpopulations. We also evaluated changes in threshold temperatures in summer and winter and correlated the findings with the risks of temperature-associated MI in the subpopulations.
Methods: We used National Health Insurance Service data for daily hospital admissions of MI, meteorological data from the Korea Meteorological Administration, and air pollution data from the National Institute of Environmental Research from 1 January 2004 to 31 December 2012. The generalized models analysis (GAM) was used to assess the short-term effects of temperature (mean, maximum and minimum thresholds) associated with MI admissions when temperatures increased above or decreased below the threshold temperature. The relationships were adjusted by humidity, barometric pressure at sea level, composition and amount of air pollutants (PM10, NO2, O3), day of the week, and duration of the heat wave or cold wave. We defined the threshold temperature as the change point detected using piecewise regression analysis with increased risk based on the relationship between temperature and MI admissions.
Results: An increased risk for hospital admission due to MI for several subpopulations was found when temperatures rose above or dropped below threshold temperatures. The threshold temperature and relative risks (RR) for MI were different according to subpopulations and season. In the summer, the threshold of mean temperatures ranged between 23.5C to 28.5C and the RRs ranged from 1.01 to 1.16 among the following subgroups: 1.16 (95% CI: 1.01-1.33) for the ≥75 years age group and 1.01 (95% CI: 0.96-1.05) for the <75 years age group, and 1.10 (95% CI: 1.02-1.20) for the urban population and 1.03 (95% CI: 0.95-1.12) for the rural population. The maximum temperature threshold ranged from 33.5C to 34.5C and the RRs ranged from 1.02 to 1.15 among the following subgroups: 1.08 RR (95% CI: 1.02-1.14) for the female group, 1.12 (95% CI: 1.01-1.24) for the ≥75 years age group, and 1.15 (95% CI: 1.04-1.28) for the Medicaid group. During winter, the RR of the Medicaid group was 1.05 (95% CI: 0.98-1.12) when the mean temperature dropped below threshold by -0.5C. The RR was 1.11 (95% CI: 1.04-1.20) at temperatures below the minimum temperature threshold (-13.5C). The RR of the urban population was 1.16 (95% CI: 1.02-1.32) and that of rural population was 1.04(95% CI: 1.00-1.08) when temperatures dropped below the minimum temperature threshold.
Conclusions: Significant increases in MI risk for several subgroups were associated with temperatures above or below the temperature threshold during summer and winter, respectively. In the summer, the female group, the ≥75 years age group, the Medicaid group, and the urban population showed the highest risk for MI when temperatures exceeded the mean and maximum temperature threshold. During winter, the Medicaid group and the urban population showed the highest risk for MI when temperatures dropped below the minimum temperature threshold. These findings identify vulnerable groups who are at increased risk for hospital admission due to MI that is related to climate change. The data can be used to establish climate change adaptation strategies for susceptible populations.
[Show abstract][Hide abstract] ABSTRACT: Background: A number of studies have examined the influence of meteorological factors and seasonal variation on the incidence of cardiovascular disease. An association between temperature and congestive heart failure or ischemic heart disease seems to be fairly robust; however, the relationship between temperature and subarachnoid hemorrhage stroke (SAH) is complex and the findings are contradictory. There has been consistent evidence for the short-term effects of ambient temperature on increased risk of myocardial infarction (MI) and death due to cardiovascular disease. However, the association between environmental temperature and risk of SAH remains controversial. Most research in SAH has concentrated on the relationship between season and incidence of SAH. It is important to include threshold temperatures, temperature lag effects, and nonlinear exposure-response relationships when evaluating the effects of temperature on stroke, MI, and acute coronary syndrome. The aim of this study was to investigate the association between the daily temperature and risk for SAH by analyzing the hospital admission records of 111,316 SAH patients from 2004 to 2012 in Korea.
Methods: We used climate variables from the Korean Meteorological Administration, air pollution data provided by Korea National Institute of Environmental Research, and SAH admission data from the National Health Insurance Service. We estimated the temperature-SAH association by applying generalized additive models (GAMs) with nonparametric smoothing functions (splines) to describe nonlinear relationships. Associations were adjusted according to humidity, barometric pressure at sea level, and air pollutants including PM10 and NO2. We estimated the threshold temperature using the piecewise-defined function. The analysis was performed for the following subgroups: gender (male or female), age (<75 years or ≥75 years), insurance type (National Health Insurance for the general population (NHI) or medical care (Medicaid) for the poor), and area (rural or urban) with climate zones based on cooling degree-days (CDD) for summer and heating degree-days (HDD) for winter. Results: We found a delayed effect, between 22-28 days, on the incidence of SAH due to hot temperature. The maximum threshold temperature during heat exposure was 31.5C. The maximum temperature increase of 1C above the threshold temperature was associated with a significant increase in relative risk (RR) of 1.07 for the >75 years age group, and 1.03 for males, respectively. Apart from longer lasting heat effects, short-term cold effects were observed between 4-7 days. The mean threshold temperature during cold exposure was -3.5C and the minimum threshold temperature was -13.5C. A mean temperature decrease of 1℃ was associated with a significant increase in RR of 1.03 for the <75 years age group, and 1.02 for females. The increased risk associated with minimum temperature was especially strong for male patients (RR =1.09, CI=1.05-1.14). With regard to heat exposure, the Medicaid group showed RR of 1.11 (lag: 1 day), which was higher than the NHI group who showed RR of 1.02 (lag: 22-28 days). With regard to cold exposure, the RRs in the Medicaid group were 1.05 with the mean temperature lag of 4-7 days, and 1.11 at the minimum temperature with a lag of 15-21 days, respectively. Meanwhile, patients in the NHI group only showed a risk of 1.01 at the mean temperature. The RR due to heat exposure was higher in hot areas with higher cooling degree-days (CDD) than in warm areas with lower cooling degree-days (CDD). Meanwhile, the RR due to cold exposure was higher in cold areas with higher heating degree-days (HDD) than in warm areas with lower heating degree-days (HDD).
Conclusions: This is the first study to find an association between temperature and incidence of SAH related to heat and cold exposure (defined by threshold temperatures). An increase in temperature above the heat temperature threshold or decrease in temperature below the cold temperature threshold correlated with increased risk of SAH in susceptible populations with different lag effects and risks. Our findings provide useful information for identifying the risk of SAH in vulnerable groups that can be used to establish climate change adaptation strategies.
[Show abstract][Hide abstract] ABSTRACT: Aim:
The inhibition of advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) mediated downstream signaling pathways have been suggested to have retinoprotective actions in diabetic retinopathy. Herein, we examined the protective effects of aminoguanidine (AG), an AGEs inhibitor, on diabetes-induced injury of retinal ganglion cells in the Zucker diabetic fatty (ZDF) rats.
Materials and methods:
Seven-week-old male ZDF rats were treated with AG (50 mg/kg body weight) once a day orally for 13 weeks. Serum and vitreous concentration of AGEs were examined. Expressions of AGEs and its receptor (RAGE) were assessed by immunohistochemistry. Southwestern histochemistry was used to detect activated nuclear factor (NF)-κB.
At the end of the study, vitreal levels of AGEs were significantly reduced in ZDF rats treated with AG. Similary, immunohistochemical analysis showed that AG significantly reduced the positive areas for AGEs and RAGE. Furthermore, AG strongly inhibited the loss of retinal ganglion cells by apoptosis. AG also suppressed the activation of to NF-κB.
Our results suggest that AG has retinoprotective properties through not only direct inhibition of AGEs formation but also downregulation of NF-κB.
[Show abstract][Hide abstract] ABSTRACT: Loss of blood-retinal barrier (BRB) properties is an important feature in the pathology of diabetic retinopathy. Endothelium integrity is important for the normal vascular function. Litsea japonica (Thunb.) Jussieu is a Korean native plant that is consumed as a vegetable food. In this study, we evaluated the ability of an ethanol extract of L. japonica to prevent retinal vascular leakages in db/db mice, which is an animal model of type II diabetes. L. japonica extracts (LJE, 100 and 250 mg/kg) were administered once a day, orally, for 12 weeks. Vehicle-treated db/db mice exhibited hyperglycemia and retinal vascular leakage. LJE treatment blocked diabetes-induced BRB breakdown and decreased retinal VEGF expression in db/db mice. LJE also inhibited the degradation of occludin, which is an important tight junction protein. These findings support the potential therapeutic usefulness of L. japonica for retinal vascular permeability diseases.
[Show abstract][Hide abstract] ABSTRACT: Retinal pathogenic angiogenesis in the eyes is a causative factor in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. This study was designed to examine the pathogenic role of the high-mobility group box-1 (HMGB1) protein and the inhibitory effect of ethyl pyruvate (EP), a well-known antioxidant substance, in retinal pathogenic angiogenesis in mice with oxygen-induced retinopathy (OIR), one of the animal models of proliferative ischemic retinopathy. The OIR mouse model was used for our in vivo studies. The mice were exposed to 75% oxygen from postnatal day 7 (P7) to P11, after which the mice were brought to room air and intraperitoneally injected with EP (50 mg/kg, or 100 mg/kg) for five days. At P17, the mice were perfused with fluorescein isothiocyanate-dextran, and flat-mounted retinas were used to measure nonperfused and neovascular tufts. In OIR mice, an intraperitoneal injection of EP reduced the nonperfused retinal area in the treatment group and significantly reduced the retinal neovascular tufts. In addition, EP inhibited the overexpression of HMGB1 in the retinas of OIR mice. These data suggest that EP could serve as an innovative pharmaceutical agent to prevent retinal neovascularization through inhibiting HMGB1 expression.
Preview · Article · Nov 2013 · Journal of Diabetes Research
[Show abstract][Hide abstract] ABSTRACT: KIOM-79, a herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix, has a strong inhibitory effect on advanced glycation end products (AGEs) formation. We investigated the beneficial effects of KIOM-79 on cardiac fibrosis in Zucker diabetic fatty (ZDF) rats. KIOM-79 (50 or 500 mg/kg/day) was orally administered for 13 weeks. AGEs formation and collagen expression in the myocardium were assessed by immunohistochemistry. The expression levels of the receptor for AGEs (RAGE), transforming growth factor- β 1 (TGF- β 1), collagen IV, fibronectin, urotensin II, and urotensin II receptor were examined in the myocardial tissue of ZDF rats. KIOM-79 treatment at 500 mg/kg inhibited the accumulation of AGEs, reduced RAGE mRNA and protein expression, and reduced the upregulation of cardiac fibrogenic factors, such as fibronectin and collagen IV, in heart of ZDF rats. Additionally, KIOM-79 ameliorated urotensin II/receptor gene expression in the cardiac tissue of ZDF rats. Our findings indicate that KIOM-79 diminishes cardiac fibrosis in ZDF rats by preventing AGEs accumulation and RAGE overexpression and by modulating the cardiac urotensin II/receptor pathway, which decreases the amount of profibrotic factors, such as TGF- β 1, fibronectin, and collagen in cardiac tissue.
Preview · Article · Nov 2013 · Evidence-based Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: Cataracts are a major cause of human blindness. Aldose reductase (AR) is an important rate-limiting enzyme that contributes to cataract induction in diabetic patients. Scopoletin is the main bioactive constituent of flower buds from Magnolia fargesii and is known to inhibit AR activity. To assess scopoletin's ability to mitigate sugar cataract formation in vivo, we studied its effects in a rat model of dietary galactose-induced sugar cataracts. Galactose-fed rats were orally dosed with scopoletin (10 or 50 mg/kg body weight) once a day for 2 weeks. Administering scopoletin delayed the progression of the cataracts that were induced by dietary galactose. Scopoletin also prevented galactose-induced changes in lens morphology, such as lens fiber swelling and membrane rupture. Scopoletin's protective effect against sugar cataracts was mediated by inhibiting both AR activity and oxidative stress. These results suggest that scopoletin is a useful treatment for sugar cataracts.
Preview · Article · Sep 2013 · Evidence-based Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: Increasing evidence indicates that advanced glycation end products (AGEs) contribute to the pathogenesis of diabetic nephropathy. The aim of this study was to investigate the protective effect of L. japonica extract (LJE) against renal damage in the db/db mouse. LJE (100 or 250 mg/kg per day) was given to diabetic mice for 12 weeks. Body weight, blood glucose levels, glycated hemoglobin (HbA1c) levels, and proteinuria were examined. In in vitro assay of the inhibition of AGE formation, immunohistochemical analysis of podocyte loss and AGE accumulations were performed. In 20-week-old db/db mice, severe hyperglycemia developed, and proteinuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. LJE treatment significantly reduced proteinuria and AGE accumulations in diabetic mice. Moreover, the loss of nephrin, an important slit diaphragm component in the kidneys, was restored by LJE treatment. Our studies suggest that LJE might be beneficial for the treatment of diabetic nephropathy. The ability of LJE to attenuate proteinuria and podocyte dysfunction may be mediated by the inhibition of AGE accumulation in the context of diabetic nephropathy in db/db mice.
Full-text · Article · May 2013 · Evidence-based Complementary and Alternative Medicine