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Metastasis is the main cause of mortality in patients with cancer. Epithelial–mesenchymal transition (EMT), a crucial process in cancer metastasis, is an established target for antimetastatic drug development. LFG-500, a novel synthetic flavonoid, has been revealed as a potential antitumor agent owing to its various activities, including modulation of EMT in the inflammatory microenvironment. Here, using a transforming growth factor beta (TGF-β)-induced EMT models, we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer, MCF-7, and lung adenocarcinoma, A549, cell lines, consistent with the observed downregulation of YAP activity. Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase (ILK), suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments, which was verified by a correlation analysis with clinical data and tumor specimens. Hence, our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.

Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.

Objective(s): Sirt3 may regulate ROS production and might be involved in β-cell apoptosis, which plays an important role in the progression of type 2 diabetes mellitus (T2DM). Quercetin is a potent anti-oxidative bioflavonoid, but its effects on T2DM remain to be explored. This study aimed to investigate the effects of quercetin on β-cell apoptosis and explore its mechanisms. Materials and Methods: The effects of quercetin were conducted on db/db mice and INS1 cells. Fasting blood glucose was determined by the colorimetric method, serum insulin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, Sirt3 in INS1 cells was knocked down by plasmid transfection. The antioxidant proteins (SOD2 and CAT), apoptosis proteins (cleaved Caspase-3, Bax, and BCL-2), and Sirt3 protein in pancreases and INS1 cells were determined by western blotting. Results: When INS1 cells and diabetic mice were treated with quercetin, the levels of SOD2, CAT, and Sirt3 proteins were increased, the levels of cleaved Caspase-3 and the ratio of Bax to BCL-2 were decreased at different degrees, along with reduced blood glucose levels and elevated insulin levels in diabetic mice. When Sirt3 was knocked down in INS1 cells, increase of two antioxidants and decrease of cell apoptosis generated by quercetin could not occur. Conclusion: Quercetin protected islet β-cells from oxidation-induced apoptosis via Sirt3 in T2DM, which would be beneficial to develop new strategies for preventing β-cell failure in T2DM.

In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of "death signal", thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide-mediated stress signaling pathways. The work presents the ability of Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture: The survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed) and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density condition.

Objective(s): Increasing evidence suggests that regular physical exercise improves type 2 diabetes mellitus (T2DM). However, the potential beneficial effects of swimming on insulin resistance and lipid disorder in T2DM, and its underlying mechanisms remain unclear. Materials and Methods: Rats were fed with high fat diet and given a low dosage of Streptozotocin (STZ) to induce T2DM model, and subsequently treated with or without swimming exercise. An 8-week swimming program (30, 60 or 120 min per day, 5 days per week) decreased body weight, fasting blood glucose and fasting insulin. Results: Swimming ameliorated lipid disorder, improved muscular atrophy and revealed a reduced glycogen deposit in skeletal muscles of diabetic rats. Furthermore, swimming also inhibited the activation of Wnt3a/β-catenin signaling pathway, decreased Wnt3a mRNA and protein level, upregulated GSK3β phosphorylation activity and reduced the expression of β-catenin phosphorylation in diabetic rats. Conclusion: The trend of the result suggests that swimming exercise proved to be a potent ameliorator of insulin resistancein T2DM through the modulation of Wnt3a/β-catenin pathway and therefore, could present a promising therapeutic measure towards the treatment of diabetes and its relatives.

Breviflavone B is a novel chiral phytoestrogen that mimics the biological functions of 17β-estradiol (E2), an estrogen which is naturally produced in our body. It has exhibited a much higher estrogen receptor (ER) bioactivity than E2 or other phytoestrogens. Breviflavone B specifically activates ER at a low dose without activating other steroid receptors, and inhibits estrogen-stimulated breast cancer cell proliferation at high doses, making it a potential treatment option for breast cancer patients. In this report, a new liquid chromatography aprroach has been developed to isolate Breviflavone B from Epimedium Brevicornum herbal extracts. After passing through DIAION HP20 resin, the ethanolic extract of Epimedium Brevicornum was firstly fractionalized by a Diol column, then further separated by a C18 column using preparative HPLC, and finally purified by an ODS-MCR-HPS column in HPLC under gradient mode. In each stage of separation, the ER bioactivities of the each fraction were measured by estrogen receptor-driven reporter gene bioassays to guide the chromatographic fractionations. The results showed that the new combination of Diol and C18 and ODS-MCR-HPS column chromatography provided better separation selectivity than our previously-reported C18 column chromatography for isolation of Breviflavon B from Epemidium herbs. Pure Breviflavon B was successfully isolated from the ethanolic extract of Epimedium Brevicornum herb via this new approach of chromatographic fractionations guided by the bioassays.

RGD peptide (Arg-Gly-Asp tripeptide) binds to integrin αVβ(3) and αVβ(5), which is selectively expressed in tumor neovasculature and on the surface of some tumor cells. Some studies showed that coupling the RGD peptides to anticancer drugs yielded compounds with increased efficiency against tumors and lowered toxicity to normal tissues. The melanoma differentiation-associated gene-7/interleukin-24 gene (mda-7/IL-24) is a novel tumor-suppressor/cytokine gene that exhibits potent tumor-suppressive activity without damaging normal cells. To enhance the antitumor effect, we inserted a glycine residue into the wild type (mda-7/IL-24) between (164)Arg and (165)Asp to form a RGD peptide, named RGD-mda-7, then expressed RGD-mda-7 in Escherichia coli. Herein, we describe the expression and purification of RGD-mda-7. We detected the characterizations of immunostimulatory activity, tumor targeting, potent cytopathic effect, and apoptosis inducing exploited by RGD-mda-7 in tumor cells, and also compared these characterizations with wtmda-7/IL-24. The data showed that RGD-mda-7 had more potent tumor targeting and apoptosis-inducing effects than wtmda-7/IL-24.

A reverse-phase liquid chromatography method with diode array detection was developed to evaluate the quality of Ginkgo biloba extract through establishing chromatographic fingerprint and simultaneous determination of eight flavonoid compounds, namely rutin, myricetin, quercitrin, quercetin, luteolin, kaempferol, apigenin, and isorhamnetin. The chromatographic separation was performed on an Agilent SB-C18 column (250 × 4.6 mm, 5.0 µm) with a gradient elution program using a mixture of methanol and 0.1% formic acid (v/v) as mobile phase within 55 min at 360-nm wavelength. The correlation coefficients of similarity for different batches of G. biloba extract from the same manufacturer and G. biloba extract from different manufacturers were determined from the LC fingerprints, and they shared a close similarity. The eight flavonoid compounds showed good regression (R 2 > 0.9995) within test ranges, and the recovery of the method was in the range of 94.1–101.4%. In addition, the content of those eight flavonoid compounds in G. biloba extract prepared by different manufacturers of China was determined to establish the effectiveness of the method. The results indicated that the developed method by having a combination of chromatographic fingerprint and quantification analysis could be readily utilized as a quality control method for G. biloba extract and its related traditional Chinese medicinal preparations.

A HPLC-DAD method was used and validated for the simultaneous determination of five flavonoids (rutin, quercitrin, quercetin, kaempferol, and isorahamnetin) in rat plasma. Chromatographic separation was performed using a Kromasil C18 column (250 × 4.6 mm, 5 µm) maintained at 35°C. The mobile phase was a mixture of methanol and 0.1% formic acid with a step linear gradient. At 1.0 mL/min flow rate, the eluent of five flavonoids were detected simultaneously at 350 nm with good separation. Under optimum conditions, good linear relationship between the peak area and the concentrations were obtained in the ranges of 0.2525 ∼ 20.2, 0.1208 ∼ 9.66, 0.1008 ∼ 20.16, 0.031 ∼ 2.46, and 0.098 ∼ 7.84 µg/mL for rutin, quercitrin, quercetin, kaempferol, and isorhamnetin, respectively. The correlation coefficient for each analyte was above 0.999. The intra-day and inter-day precisions were better than 7% and 10%. The detection limit (S/N = 3) for rutin, quercitrin, quercetin, kaempferol, and isorhamnetin were 0.01...

Aim: To observe the effects of Ginkgo biloba extract (EGb) on the hypertrophy of mesangial cells and the accumulation of extracellular matrix (ECM) in mesangial cells. Methods: Cultured mesangial cells were allotted into 7 groups: normal group, solvent control group, high glucose group, low dose of EGb group, moderate dose of EGb group, high dose of EGb group, and captopril group. Activities of cell antioxidases, S phase percentage and G0/G1 phase percentage, collagen IV and laminin, Smad2/3 and Smad7, TGF-β1 mRNA were measured by different methods. Results: For EGb-treated groups, when compared with high glucose group, the cell percentage of S phase was raised and the percentage of G0/G1 was lowered. The intensity of oxidative stress was weakened. The expression of Smad2/3 was greatly decreased and Smad7 was increased. Collagen IV, laminin and TGF-β1 mRNA were also reduced. Conclusion: EGb can suppress cell hypertrophy and the accumulation of ECM in rat mesangial cells, which means it could play a vital role in the delay of glomerulosclerosis in diabetic nephropathy.

The anticancer agent genistein inhibits cell growth of tumor cell lines from various malignancies. In our study, we investigated the effectiveness of combined treatment of ionizing radiation (IR) with genistein on cervical HeLa cells and its possible mechanism. It was found that the inhibitory rate in cells with combined treatment was significantly higher than that of the cells treated with IR or genistein alone. After treatments of IR (4 Gy) combined with genistein (40 µmol/L), the apoptotic index of the cells was significantly increased and the cells were arrested in the G2/M phase. Survivin mRNA expression increased after IR (4 Gy), while it significantly decreased after combined treatment. These findings indicated that genistein enhanced the radiosensitivity of cervical cancer HeLa cells, and the mechanisms for this action might include increase of apoptosis, decrease of survivin expression, and prolongation of cell cycle arrest. Keywords:: genistein, ionizing radiation, survivin, apoptosis, cell cycle

Hydrophilic interaction chromatography (HILIC) is an emerging separation mode of liquid chromatography (LC). Using highly hydrophilic stationary phases capable of retaining polar/ionic metabolites, and accompany with high organic content mobile phase that offer readily compatibility with mass spectrometry (MS) has made HILIC an attractive complementary tool to the widely used reverse-phase (RP) chromatographic separations in metabolomic studies. The combination of HILIC and RPLC coupled with an MS detector expands the number of detected analytes and provides more comprehensive metabolite coverage than use of only RP chromatography. This review describes the recent applications of HILIC-MS/MS in metabolomic studies, ranging from amino acids, lipids, nucleotides, organic acids, pharmaceuticals, and metabolites of specific nature. The biological systems investigated include microbials, cultured cell line, plants, herbal medicine, urine, and serum as well as tissues from animals and humans. Owing to its unique capability to measure more-polar biomolecules, the HILIC separation technique would no doubt enhance the comprehensiveness of metabolite detection, and add significant value for metabolomic investigations. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:574-600, 2016.

This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB.

A rapid and useful approach for screening potential bioactive components in Ginkgo biloba extract (GBE) with preventive effect against diabetic nephropathy (DN) was developed using mesangial cells extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Mesangial cells were first divided into two groups according to their treatments with high glucose or high glucose plus GBE. After incubation for 4, 8, 12, 16, 24 and 48 h, the cells were harvested and extracted with 40% acetic acid in water before LC-MS/MS analysis. Then, 19 compounds and five metabolites were found to selectively combine with mesangial cells. Notably, compounds including quercetin and rutin were identified or tentatively characterized according to the results of retention time and MS spectra, which is highly consistent with our previous reports that quercetin and rutin are potent protective agents against glomerulosclerosis in DN. Therefore, all these results indicate that target cell extraction coupled with LC-MS/MS analysis can be successfully applied for predicting the bioactive components in GBE with preventive effect against DN.

A new type of 4-isopropylcalix[4]arene-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)propylsilyl-appended silica particles (IPC4CD-HPS) has been prepared by treatment of bromoacetate-substituted (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)propylsilyl-appended silica particles (BACD-HPS) with 4-isopropylcalix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The bonded silica IPC4CD-HPS has been successfully used as chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phase was characterized by means of elemental analysis and Fourier transform infrared spectroscopy. This new CSP has a chiral selector with two anchored functional moieties: 4-isopropylcalix[4]arene and β-cyclodextrin. The chromatographic performance of IPC4CD-HPS was investigated by separation of positional isomers of several disubstituted benzenes and enantiomers of some chiral drug compounds under reversed-phase conditions. The results showed that IPC4CD-HPS had excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds due to the cooperative functioning of the anchored 4-isopropylcalix[4]arenes and β-cyclodextrins.

Urotensin II (UII), a somatostatin-like cyclic peptide, was originally isolated from the fish urophysis. Our previous study showed that UII stimulates the proliferation of A549 lung adenocarcinoma cells and promotes tumor growth in a nude mouse xenograft model, suggesting that UII may contribute to the pathogenesis of lung adenocarcinoma. In this study, the underlying mechanism for UII to promote lung adenocarcinoma growth was explored by observing the effect of UII on the tumor inflammatory microenvironment in tumor-bearing nude mice. Immunohistochemical analysis showed that UII promoted the infiltration of CD68(+) tumor-associated macrophages (TAMs) in the tumor micro-environment. Enzyme-linked immunosorbent assay (ELISA) demonstrated that UII promoted the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9). Western blot analysis showed that UII promoted the activation of nuclear factor-κB (NF-κB). These findings suggest that the enhanced levels of IL-6, TNF-α and MMP-9 in the tumor microenvironment, which likely resulted from increased activation of NF-κB induced by UII, may be one of the important mechanisms by which UII promotes lung adenocarcinoma growth. These findings imply that antagonists of UII or urotensin II-receptor (UT-R) have potential for the prevention and treatment of lung adenocarcinoma.

Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) has shown potent tumor cell apoptosis inducing capacity in multiple cancers. However, the apoptosis induction capacity of mda-7/IL-24 was low and directly correlated with the adhesion to tumor cells.Cell adhesion molecule integrin α(v)β(3) expressed on the surface of several types of solid tumor cells, and they bind to arginine-glycine-aspartic acid (RGD) which enhanced the adhesion to tumor cells. This rout was exploited to construct a tumor-targeting gene RGD-IL-24 which can express RGD-MDA-7/IL-24 protein that includes the cell adhesive sequence (164)Arg-(165)Gly-(166)Asp (A Glycine residue was inserted into the recombinant MDA-7/IL-24 between Arg164 and Asp165 to form a RGD motif). We successfully got the MDA-7/IL-24 mutant by overlapping polymerase chain reaction (PCR) and evaluated its therapeutic efficacy for tumor cell lines MCF-7, HeLa, HepG2, and normal human lung fibroblast (NHLF) line. And we found that the expression of pCDNA3.1/RGD-IL-24 was same to the expression of pCDNA3.1/IL-24. The RGD-IL-24 enhanced the apoptosis-inducing function in tumor cells, but not in normal cells. In tumor cell lines, the apoptosis-inducing activities of RGD-IL-24 was significantly higher than IL-24 detecting by MTT assay, Annexin V, and Hoechst 33258 analysis. Further, pCDNA3.1/RGD-IL-24 showed a significant increase in the ratio of pro-apoptotic (bax) to anti-apoptotic (bcl-2) proteins in tumor cell lines, but not in NHLF cell line. Together, these results suggest that RGD-IL-24 can enhance the apoptosis of tumor cells and may provide a promising drug in tumor therapy.

To investigate the chemical constituents of Kalopanax septemlobus.Chromatographic techniques including silica gel, gel, semi-preparative HPLC and PTLC as well as recrystallization were employed in the isolation and purification, and the structures were elucidated by spectral analysis and physical and chemical properties.6 compounds were identified as liriodendrin (1), (-) -syringarenol (2), trans-coniferyl aldehyde (3), trans-caffeic acid (4), beta-daucosterol (5), beta-sitosterol (6).Compounds 2 -5 are obtained from this genus for the first time.

The expression of the human Ki-67 protein, which is strictly associated with cell proliferation, is regulated by a variety of cellular mediators. In this study, we studied the effects of p53 on Ki-67 promoter in HeLa cells using luciferase reporter assay. The results showed that: (1) p53 inhibited Ki-67 promoter activity in a dose-dependent manner, (2) the p53-binding motifs mediated part of the transcriptional repression of Ki-67 promoter through a sequence-specific interaction with p53, (3) p53 was able to repress the Sp1-stimulated Ki-67 promoter activity, and (4) the Sp1-binding sites were responsible for the p53-mediated transcriptional repression of Ki-67 promoter. In conclusion, p53 inhibited Ki-67 promoter activity via p53- and Sp1-dependent pathways, and the interaction between p53 and Sp1 might be involved in the transcriptional regulatory mechanisms.

The protective effect of rutin on the glomerulosclerosis of diabetic nephropathy (DN) in rat mesangial cells was investigated. The cultured mesangial cells were divided into eight groups: normal, solvent control, high glucose, low dose of rutin, moderate dose of rutin, high dose of rutin, captopril and Ginkgo biloba extract. The cell cycles, type IV collagen and laminin in cytoplasm, TGF-β₁ mRNA of mesangial cells, Smad 2/3 and Smad 7, and the activities of four antioxidant indexes including T-SOD, MDA, CAT and GSH-Px were measured by flow cytometry, radioimmunoassay, RT-PCR, western blotting and visible spectrophotometry, respectively. Compared with the high glucose group, rutin decreased the cell percentages of the G₀/G₁ phase and inhibited the expression of Smad 2/3, laminin and type IV collagen, and TGF-β₁ mRNA level, significantly. The antioxidant capacity, the cell percentages of S phase and Smad 7 expression were significantly increased by rutin. These results suggest that rutin is a potent protective agent against glomerulosclerosis in DN.

To investigate the protective effects of Ginkgo biloba extract (GBE) on high glucose-induced apoptosis of human lens epithelial cells (HLEC) and the possible molecular mechanisms.The cultured HLEC were allotted into 6 groups: normal group, high glucose group, low-, moderate-, and high-dose GBE group, and the bendazac lysine group. Cell viability, cell apoptosis, the activities of cell antioxidases, aldose reductase, caspase-3, the levels of cell antioxidants, and the expressions of Bcl-2 and Bax were assessed by different methods.After being incubated with high glucose for 24 h, HLEC underwent apoptosis and exhibited significant oxidative stress. In the presence of GBE at different doses, the rate of HLEC apoptosis was lower and the oxidative stress state was significantly ameliorated. The increased ratio of Bax to Bcl-2 was significantly reduced and the activation of caspase-3 was suppressed by GBE in a dose-dependent manner.GBE prevents HLEC from high glucose-induced apoptosis through inhibiting oxidative stress, reducing the ratio of Bax to Bcl-2, and decreasing the activity of caspase-3. Therefore, GBE has a potential protective effect against diabetic cataract formation.

1. Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)-ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN.

It has been known that oxidative stress plays an important role in the development of diabetic nephropathy (DN). The antioxidative effects of Astragalus saponin I (AS I) were studied in vitro and in vivo. In the presence of high glucose and H2O2, the total antioxidative capability, catalase, reduced glutathione, and superoxide dismutase level of rat mesangial cells were significantly decreased, and transforming growth factor β1 (TGF-β1) mRNA level, collagen IV, and laminin level were significantly increased. When compared with those in the high glucose group, these 4 indexes of cells incubated in 2.0 and/or 20 µmol/L of AS I were significantly enhanced, and levels of TGF-β1 mRNA, collagen IV and laminin were statistically decreased. By flowcytomery, percentages of S phase of cells incubated in high glucose and H2O2 were lowered, while those in AS I were increased. Furthermore, the physical behaviors of rats treated with 12 mg/kg of AS I restored with vigor and weight gaining, while the level of HbAlC was significantly reduced. Thus, AS I has antioxidative effects and is a potential compound worth further study because it may prevent the development of DN. Keywords:: Astragalus saponin I, diabetic nephropathy, antioxidative, mesangial cell

To investigate the preventive and protective effects of bendazac lysine (BDL) on experimental early diabetic nephropathy (DN) rats.After an early DN model was induced by streptozotocin, rats were administered BDL at doses of 100, 200, and 400 mg/kg for 8 weeks. Blood glucose, microalbuminuria, kidney index, total antioxidative capacity, laminin, advanced glycation end products (AGE), aldose reductase (AR) activity, and the relative quantity of transforming growth factor beta1 (TGF- beta1) mRNA were measured by different methods. The ultrastructural morphology was observed by transmission electron microscope.The physical behaviors of early DN rats were hypopraxia, cachexia, and polyuria, while those treated with high doses of BDL were vibrant and vigorous. For BDL-treated DN rats, when compared with vehicle-treated DN rats, the blood glucose level and the intensity of oxidative stress were ameliorated. Also, the microalbuminuria level, AGE either in serum or in renal, and AR activity were significantly reduced. Furthermore, the expression of TGF-beta1 mRNA in the kidney cortex was declined and the thickness of glomerular base membrane was decreased significantly. The ultrastructure of glomerulus and mesangial matrix of BDL-treated DN rats were ameliorated.BDL has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.

Diabetic nephropathy (DN) has become the leading cause of end stage failure, but no renoprotective treatment has been very available for use in DN. Astragalus saponin I (AS I), a component extracted from Astragalus membranaceus BUNGE, was studied in experimental DN induced by administration of streptozotocin in male rats. The early DN rats were treated with 3 doses of AS I for 8 weeks to analyze its efficacy with different parameters. By comparison with vehicle-treated DN rats, the renal hypertrophy, the oxidative stress intensity, and the blood glucose level of DN rats were ameliorated by AS I. Also, the microalbuminuria level, advanced glycated end-products either in serum or in kidney cortex, and the aldose reductase activity were significantly reduced. Furthermore, the expression of transforming growth factor β1 mRNA in kidney cortex by RT-PCR analysis was markedly declined. Both the relative grade of mesangium hyperplasia by microscopical observation and the thickness of glomerular base membrane by electron microscope measurement were decreased significantly. Therefore, the results suggest that AS I has therapeutic effects on several pharmacological targets in the progress of DN and is a potential drug for prevention of early stage DN. Keywords:: Astragalus membranaceus, Astragalus saponin I, diabetic nephropathy