• Journal of Acupuncture Research
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• v.19 no.4
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• pp.152-166
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• 2002

Objective : This study was undertaken to determine whether Hominis Placenta(HP) aqua-acupuncture exerts renoprotective effect on diabetic nephropathy induced by streptozotocin(STZ) in rats. Methods : In order to study the renoprotective effect of HP aqua-acupuncture, experimental animals were divided into 5 groups and treated for 2 weeks as follows: control group was injected subcutaneously by saline aqua-acupuncture into Sinsu(BL23) in STZ induced diabetic rats, 5% HP aqua-acupuncture group was injected subcutaneously by 5% HP aqua-acupuncture into Sinsu(BL23) in STZ induced diabetic rats, 10% HP aqua-acupuncture group was injected subcutaneously by 10% HP aqua-acupuncture into Sinsu(BL23) in STZ induced diabetic rats, normal group was injected subcutaneously by saline aqua-acupuncture into Sinsu(BL23) in normal rats, and Captopril group was administrated with captopril at a dose of 50mg/kg in STZ induced diabetic rats. Results : While HP aqua-acupuncture did not reduce any body weight, index of kidney hypertrophy, the plasma glucose concentration and BUN respectively, HP aqua-acupuncture showed lowering urinary albumin excretion rate and serum creatinine as compared with the control group. Gene and protein expressions of $TGF-{\beta}1$ and fibronectin in kidney, one of the extracellular matrix proteins were investigated. There were significant differences in expression levels in HP aqua-acupuncture group as compared with the control group, and $100{\mu}g/m{\ell}$ and $500{\mu}g/m{\ell}$ of HP depressed apoptosis, showing in a dose dependent manner. In the HE staining, HP aqua-acupuncture inhibited the injury of glomerulus and proximal convoluted tubule. Conclusions : HP aqua-acupuncture showed the renoprotective effect possibly through suppressions of $TGF-{\beta}1$ and fibronectin expressions in kidney.

• Journal of Ginseng Research
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• v.36 no.3
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• pp.256-262
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• 2012

Reactive oxygen species play critical role in kidney damage. Free radical-scavenging activities of Panax ginseng are known to be increased by heat-processing. The structural change of ginsenoside and the generation of Maillard reaction products (MRPs) are closely related to the increased free radical-scavenging activities. In the present study, we have demonstrated the Maillard reaction model experiment using ginsenoside Re and glycine mixture to identify the renoprotective effect of MRPs from ginseng or ginsenosides. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg2, Rg6 and F4 by heat-processing. The free radical-scavenging activity of ginsenoside Re-glycine mixture was increased in a temperature-dependant manner by heatprocessing. The improved free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant MRPs which led to the protection of LLC-PK1 renal epithelial cells from oxidative stress. Although the free radical scavenging activities of less-polar ginsenosides were weak, they could protect LLC-PK1 cells from oxidative stress. Therefore, MRPs and less-polar ginsenosides contributed to the combined renoprotective effects against oxidative renal damage.

• Biomedical Science Letters
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• v.14 no.1
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• pp.19-26
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• 2008

This study investigated the effect of Rehmanniae Radix preparata extract on the antioxidant enzymes of kidney and renal function in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into three groups including normal control (NC), diabetic control (DC), and diabetic treatment with Rehmanniae Radix preparata (DRR). Over a 4-week study period, Rehmanniae Radix preparata aqueous extract was administered orally at 1124 mg/kg BW/day. The serum glucose level in the DRR group was significantly lower (P<0.05) than the DC group. The serum blood urea nitrogen in diabetic groups was significantly higher (P<0.001) than the NC group. The urinary total protein level in the DRR group was significantly lower (P<0.05) than the DC group. The renal xanthine oxidase activity in the DRR group was significantly lower (P<0.01) than the DC group. The renal catalase activity in the DC group was significantly lower (P<0.05) compared to the NC group and that was significantly higher (P<0.05) in the DRR group than the DC group. In conclusion, these results indicated that Rehmanniae Radix preparata can prevent or retard the development of diabetic nephropathy via its beneficial effects for correcting the hyperglycemia and favorable effects on antioxidant enzyme system.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.57-61
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• 2002

The renoprotective activities of white ginseng radix and rootlet were compared in spontaneously hypertensive rat (SHR) with diabetes. During oral administration of white ginseng radix (Ginseng Radix Alba, GRA) and white ginseng rootlet (Ginseng Radix Palva, GRP) for four weeks, arterial blood pressure and blood glucose levels were determined at every 10 days. In both GRA- and GRP-treatment groups, arterial blood pressures started to go down after 10 days of administration and maintained throughout the study period. After four weeks administrations of GRA and GRP, diastolic blood pressures were significantly decreased with 17% and 9%, respectively. GRA treatment also decreased blood glucose levels after 10 days of administration when compared with diabetic SHR group. At the end of the experiment, serum creatinine (Scr) and blood urea nitrogen (BUN) were not significantly different between the groups, except 62% higher value of BUN in diabetic SHR group when compared with SHR group. In the diabetic SHR group, the excretion of urinary albumin was increased significantly when compared with SHR. The level of urinary albumin in GRA treated group was markedly reduced when compared with diabetic SHR group $(67.8{\pm}4.7\;vs.\;131.3{\pm}13.5\;mg/24\;h).$ To examine the effects of ginseng radices on an overt diabetic nephropathy, index of kidney hypertrophy and transforming growth $factor-{\beta}1\;(TGF-{\beta}1)$ protein levels were evaluated. The glomerular and tubular cells stained positive for $TGF-{\beta}1$ seemed to be more abundant in diabetic SHR than in those with SHR, and GRA treated rats showed somewhat less $TGF-{\beta}1$ protein in glomerular and tubular cells when compared with diabetic SHR. Our results suggest that GRA might be a useful antihypertensive and antidiabetic agent with renoprotective effect.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.1-11
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• 2021

Objectives: Nephrotic syndrome is a kidney disorder, which is characterized by proteinuria, edema (swelling), and hyperlipidemia. Maydis Stigma (Corn silk) has been widely used in Asia as a traditional medicine and is known to have a diuretic effect and is used for the treatment of edema and indigestion. Methods: The aim of this study is to investigate the improvement effect of Maydis Stigma in treating nephrotic syndrome induced by puromycin aminonucleoside. Sprague-Dawley rats were intravenously injected with 75 mg/kg/day puromycin aminonucleoside, then treated with either Losartan or 200 mg/kg/day Maydis Stigma for seven days. Results: Maydis Stigma significantly decreased ascites and proteinuria level. Plasma levels of blood urea nitrogen (BUN) and plasma creatinine reduced significantly by Maydis Stigma. In addition, treatment with Maydis Stigma attenuated histological damage. Treatment with Maydis Stigma also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Conclusions: Maydis Stigma ameliorates kidney injury in nephrotic syndrome rat models. Maydis Stigma exerts a renoprotective effect owing to its anti-inflammatory effects and reductions of ascites and proteinuria. Thus, these results indicate that Maydis Stigma is likely to be a promising agent in the treatment of nephrotic syndrome.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.599-610
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• 2023

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

• Toxicological Research
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• v.27 no.1
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• pp.37-41
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• 2011

This study investigated the antioxidative action of Corni Fructus aqueous extract on kidneys of diabetic mice. The electron donating abilities of Corni Fructus aqueous extract and its antioxidant activities (XO, SOD, CAT, GST, eNOS) in kidneys of C57BL/6 or db/db mice were evaluated. For in vivo study, seven week-old male mice were divided into normal control group (NC, C57BL/6 mice), diabetic control group (DC, db/db mice) and Corni Fructus (500 mg/kg/day for 8 weeks) treated diabetic group (DCF, db/db mice). The electron donating abilities of Corni Fructus aqueous extract exhibited 7%, 24.4%, and 42.7% at concentrations of 100, 500, and $1000\;{\mu}g/ml$, respectively. The activity of XO in the DCF group was significantly lower than the DC group by 35% (p < 0.05). The SOD activity was significantly higher in the DCF group than the DC group by 26% (p < 0.05). The activities of CAT and GST were lowered in the DCF group than the DC group by 26% (p < 0.05) and 7.6%, respectively. The mRNA expression of eNOS in kidneys was lower in the DCF group than the DC group by 24%. These results indicate that Corni Fructus reduced oxidation stress as evidenced by the restoration of the enzymatic antioxidative defense system in renal tissues of db/db mice. It is suggested that these antioxidative actions of Corni Fructus on renal tissues in db/db mice could contribute to its renoprotective effects on diabetic nephropathy.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.619-628
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• 2023

In the modern era, chronic kidney failure due to diabetes has spread across the globe. Prunetin (PRU), a component of herbal medicines, has a broad variety of pharmacological activities; these may help to slow the onset of diabetic kidney disease. The anti-nephropathic effects of PRU have not yet been reported. The present study explored the potential nephroprotective actions of PRU in diabetic rats. For 28 days, nephropathic rats were given oral doses of PRU (20, 40, and 80 mg/kg). Body weight, blood urea, creatinine, total protein, lipid profile, liver marker enzymes, carbohydrate metabolic enzymes, C-reactive protein, antioxidants, lipid peroxidative indicators, and the expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 2 (GLUT-2) mRNA genes were all examined. Histological examinations of the kidneys, liver, and pancreas were also performed. The oral treatment of PRU drastically lowered the blood glucose, HbA1c, blood urea, creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, lipid profile, and hexokinase. Meanwhile, the levels of fructose 1,6-bisphosphatase, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase were all elevated, but glucose-6-phosphate dehydrogenase dropped significantly. Inflammatory marker antioxidants and lipid peroxidative markers were also less persistent due to this administration. PRU upregulated the IRS-1 and GLUT-2 gene expression in the nephropathic group. The possible renoprotective properties of PRU were validated by histopathology of the liver, kidney, and pancreatic tissues. It is therefore proposed that PRU (80 mg/kg) has considerable renoprotective benefits in diabetic nephropathy in rats.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.227-231
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• 2017

Background: Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). Methods: The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells. Results: As a result, ginsenoside Rh3 shows a stronger protective effect than that shown by Rk2. Cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment also significantly reduced after cotreatment with ginsenoside Rh3. Conclusion: These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.

• Journal of Pharmacopuncture
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• v.24 no.1
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• pp.1-13
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• 2021

Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. It has a variety of valuable pharmacological and therapeutic activities including antioxidant, anti-inflammatory, anti-diabetic and anti-tumor. These pharmacological impacts have been demonstrated in in vitro and in vivo studies. Also, clinical trials have revealed the efficacy of troxerutin for management of phlebocholosis and hemorrhoidal diseases. In the present review, we focus on the therapeutic effects and biological activities of troxerutin as well as its molecular signaling pathways.