Rosiglitazone Group Research Articles

PPAR-γ regulates the polarization of M2 macrophages to improve the microenvironment for autologous fat grafting.

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR-γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR-γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment.

Targeting microbiota–immune–synaptic plasticity to explore the effect of tea polyphenols on improving memory in the aged type 2 diabetic rat model

ABSTRACT Objectives The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis. Methods The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study. Results Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes. Discussion TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.

A comparative study of the benefits of monotherapy rosiglitazone versus rosiglitazone with insulin in streptozotocin-induced diabetes in rats

Background: Diabetes is often associated with dyslipidemia, where plasma lipid and lipoprotein profile alterations increase the risk of coronary heart disease. Insulin resistance increases the risk of hyperinsulin and atherosclerosis, developing hypertension and diabetes. Patients with diabetes suffer from metabolic disorders in carbohydrates, fat, and proteins associated with hyperglycemia. Hence reducing insulin resistance is a therapeutic approach to treating diabetes. Aims and Objectives: The aim of the study was to evaluate the beneficial effects of monotherapy rosiglitazone, gemfibrozil, and insulin versus rosiglitazone, gemfibrozil, and insulin combination in streptozotocin-induced diabetes in rats. Materials and Methods: 42-Wistar rats of either sex were used in this study, except for the control group, streptozocin was used to induce diabetes. These rats were further allocated into five groups, each group consists of eight animals. Blood serum was used to estimate blood glucose and serum lipid levels were observed after a period of 6 weeks. Results were analyzed using SPSS software version 21.0. Results: Combination therapy of insulin + rosiglitazone + gemfibrozil showed a significant decrease in serum blood glucose, lipid levels in compared with vehicle and rosiglitazone groups. Conclusion: The results of our study demonstrated a more favorable lipid profile than the monotherapy regimen; adding gemfibrozil and insulin to rosiglitazone could help reverse the cardiovascular adverse events it causes.

Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene-2,4-thiazolidinediones as partial PPAR-γ agonists

Peroxisome proliferator-activated receptor-γ (PPAR-γ) partial agonists or antagonists, also termed as selective PPAR-γ modulators, are more beneficial than full agonists because they can avoid the adverse effects associated with PPAR-γ full agonists, such as weight gain and congestive heart disorders, while retaining the antidiabetic efficiency. In this study, we designed and synthesized new benzylidene-thiazolidine-2,4-diones while keeping the acidic thiazolidinedione (TZD) ring at the center, which is in contrast with the typical pharmacophore of PPAR-γ agonists. Five compounds (5a–e) were designed and synthesized in moderate to good yields and were characterized using spectral techniques. The in vivo antidiabetic efficacy of the synthesized compounds was assessed on streptozotocin-induced diabetic mice using standard protocols, and their effect on weight gain was also studied. Molecular docking and molecular dynamics (MD) simulation studies were performed to investigate the binding interactions of the title compounds with the PPAR-γ receptor and to establish their binding mechanism. Antidiabetic activity results revealed that compounds 5d and 5e possess promising antidiabetic activity comparable with the standard drug rosiglitazone. No compound showed considerable effect on the body weight of animals after 21 days of administration, and the findings showed statistical difference (p < 0.05 to p < 0.0001) among the diabetic control and standard drug rosiglitazone groups. In molecular docking study, compounds 5c and 5d exhibited higher binding energies (− 10.1 and − 10.0 kcal/mol, respectively) than the native ligand, non-thiazolidinedione PPAR-γ partial agonist (nTZDpa) (− 9.8 kcal/mol). MD simulation further authenticated the stability of compound 5c-PPAR-γ complex over the 150 ns duration. The RMSD, RMSF, rGyr, SASA, and binding interactions of compound 5c-PPAR-γ complex were comparable to those of native ligand nTZDpa-PPAR-γ complex, suggesting that the title compounds have the potential to be developed as partial PPAR-γ agonists.

The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways

Objective GuizhiFulingWan (GFW) has been reported to be effective against polycystic ovary syndrome (PCOS) by possessing oxidative stress and inflammation which related to PI3K/AKT/NF-κB, Nrf2/HO-1 pathway. This study aims to probe the effects and mechanisms of GFW combined with rosiglitazone on PCOS via PI3K/AKT/NF-κB and Nrf2/HO-1 pathways. Methods A rat PCOS model established by dehydroepiandrosterone (DHEA) injection. The experiment was allocated to control, DHEA, GFW, rosiglitazone, GFW + rosiglitazone groups. Treatment for 30 days, we monitored weight and ovarian weight of rats. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), lipid metabolism indexes, estrous cycle and sex hormone-, inflammation-, oxidative stress-related factors were examined. Hematoxylin&eosin staining assessed ovarian tissue pathological changes. Western blot determined PI3K/AKT/NF-κB, Nrf2/HO-1 pathways-related markers. Results GFW and rosiglitazone treatment suppressed body weight and ovarian weight in PCOS rats. They also decreased FBG, FINS, HOMA-IR while inhibited total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and enhanced high-density lipoprotein (HDL). They ameliorated estrous cycle, ovarian histological changes and follicular development. They restrained testosterone (T), luteinizing hormone (LH) and accelerated estradiol (E2), progesterone (P), follicle stimulating hormone (FSH). They inhibited glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD) in serum while increased GSH-Px, SOD and decrease MDA in ovarian tissues. They reduced C-reactive protein, interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), IL-6, IL-1β levels. GFW and rosiglitazone co-intervention regulated PI3K/AKT/NF-κB and Nrf2/HO-1 pathways in PCOS rats. Conclusion GFW alleviated ovarian dysfunction in PCOS rats, which may be related to the PI3K/AKT/NF-κB, Nrf2/HO-1 pathways.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

Intra-hematoma Rosiglitazone infusion therapy attenuates blood-brain barrier disruption after intracerebral hemorrhage in rabbits

ObjectiveTo observe the effect of intra-hematoma Rosiglitazone (RSG) infusion therapy in treating intracerebral hemorrhage (ICH). Specifically, to explore the effects of RSG on tight junction associated proteins Occludin and ZO-1 expression within perihematomal brain tissues as well as the blood–brain barrier (BBB) permeability after ICH in rabbits. MethodsA total of 30 rabbits were randomly assigned to three groups including sham control group (NC group, n = 10), hemorrhage model group (HM group, n = 10), and hemorrhage model with RSG treatment group (RSG group, n = 10). ICH was induced in rabbits of HM group and RSG group, involving an injection of autologous non-anticoagulant artery blood (0.3 mL, similar to basal ganglia hematoma 30 mL in humans) into the left basal ganglia of the rabbits’ brains. The NC group was injected with the same amount of saline into the same area. Six hours later after ICH induction or sham surgery, the RSG group received the intra-hematoma RSG (0.5 mg/0.1 mL) infusion, meanwhile the NC group and the HM group were injected with saline (0.1 mL) into the hematoma area. On day seven, the perihematomal brain tissues were obtained to determine the Occludin and ZO-1 expressions by Western Blot and RT-PCR, and the BBB permeability by the Evan’ s Blue (EB) content. ResultsOccludin and ZO-1 expressions and mRNA levels were all significantly decreased in the HM group and RSG group compared with the NC group (P < 0.01). Occludin and ZO-1 expressions and mRNA levels were all significantly increased in the RSG group compared with the HM group (P < 0.01). The EB contents were all significantly increased in the HM group and RSG group compared with the NC group (P < 0.01). The EB content was significantly decreased in the RSG group compared with the HM group (P < 0.01). ConclusionIntra-hematoma RSG infusion therapy could increase the expressions of tight junction associated proteins Occludin and ZO-1 in the perihematomal brain tissues and decrease the BBB permeability in rabbits after ICH.

Rosiglitazone Protects against Acetaminophen-Induced Acute Liver Injury by Inhibiting Multiple Endoplasmic Reticulum Stress Pathways.

Excessive acetaminophen (APAP) use can lead to acute liver injury (ALI) by inducing endoplasmic reticulum stress (ERS). We previously found that pretreatment with the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand rosiglitazone (RSG) alleviated ALI in APAP-treated mice. To examine if RSG-mediated hepatoprotection is associated with ERS suppression. Forty-eight male CD-1 mice were randomly divided into control, RSG, APAP 4 h, APAP 24 h, RSG + APAP 4 h, and RSG + APAP 24 h groups. The RSG and RSG + APAP groups received RSG (20 mg/kg) by gavage 48, 24, and 1 h before intraperitoneal injection of 300 mg/kg APAP, while the APAP group received APAP alone and the control group received only normal saline. Animals were sacrificed immediately (RSG and control groups), 4 h (APAP 4 h and RSG + APAP 4 h), or 24 h (APAP 24 h and RSG + APAP 24 h) post-APAP injection. Liver tissues were collected for hematoxylin-eosin staining, TUNEL staining, and Western blotting for ERS-associated proteins. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured. A second cohort received APAP or RSG + APAP as described and were monitored for survival over one week. At 4 and 24 h following APAP injection alone, serum ALT and AST levels were significantly elevated, and central lobular necrosis of the liver was observed. Necrosis area reached 21.7% at 4 h and 32.1% at 24 h post-APAP, while apoptotic fractions reached 25.6% and 32.4%. Further, 50% of mice in the survival analysis cohort died within one week post-APAP. At 4 h post-APAP, the ERS marker glucose-regulated protein-78 (GRP78) and ERS-associated proteins pJNK, GRP78, p-eIF2α, pPERK, and pIRE were all significantly upregulated. Pretreatment with RSG significantly reduced serum ALT and AST, liver necrosis area, apoptosis rate, and expression of ERS-associated proteins compared to APAP alone, while increasing survival to 80%. Rosiglitazone pretreatment can alleviate APAP-induced ALI by suppressing three branches of ERS signaling.

Rosiglitazone Alleviates Contrast-Induced Acute Kidney Injury in Rats via the PPARγ/NLRP3 Signaling Pathway.

Background This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.

Dietary fiber konjac glucomannan exerts an antidiabetic effect via inhibiting lipid absorption and regulation of PPAR-γ and gut microbiome

Konjac glucomannan’s influence on the regulation of diabetes mellitus, hyperlipidemia, and gut microbial flora was evaluated in this study. In addition, a high-fat diet and streptozotocin were used to induce type 2 diabetes mellitus in rats. At the end of the study, we analyzed various parameters such as body weight, plasma lipid profile, insulin levels by immunohistochemistry, degree of fibrosis in the liver, protein expression of PPAR-γ and p-SREBP-1C and gut microbial changes using 16S rRNA sequencing. The results of our study suggest that KGM supplementation significantly reduced the plasma lipid profile (TC, TG, VLDL, LDL, etc.). In addition, KGM has improved insulin levels, which were visualized using immunohistochemistry. Furthermore, KGM also regulated the protein expression of key regulatory proteins of lipid metabolism PPAR-γ and p-SREBP-1C (Group 3). Similar results were seen in the groups treated with the standard drug rosiglitazone (group 4). Finally, the 16S rRNA sequencing shows that KGM contributes to gut microbiota composition alterations, and it was observed using the Simpson, Shannon, Chao-1, and actual otus indices (group 3). KGM further alters the production of beneficial SCFAs and helps host good health. Furthermore, several metabolic pathways have been activated in T2DM rats. As a result, it becomes apparent that the digestive system's microbiome will play a role in T2DM. KGM has various health advantages but is particularly useful in treating hyperlipidemia and diabetes.

Protective effect of rosiglitazone on microscopic and oxidative stress parameters of ram sperm after freeze-thawing

The purpose of this study was to investigate the effects of rosiglitazone on ram semen after cryopreservation on the quality of thawed sperm. Sperm motility, membrane functionality, viability, total abnormality, acrosome membrane integrity, mitochondrial activity, reactive oxygen species production, ATP content and apoptotic features were assessed after thawing. Rosiglitazone at concentration of 60 µM resulted in the highest (P < 0.05) total motility, progressive motility and straight-line velocity. The percentages of average path velocity and curvilinear velocity were greater in the 60 µM group. Different concentrations of rosiglitazone did not have significant effects on amplitude of the lateral head displacement, linearity and straightness. The highest amounts of membrane functionality and mitochondrial activity after freeze-thawing were observed in groups containing 60 µM. By increasing the rosiglitazone level to 80 µM, no positive effect was observed in most of the evaluated parameters. The lowest ROS concentration was recorded in 60 µM rosiglitazone group (P < 0.05). The group containing 60 µM rosiglitazone also produced the lowest significant percentage of apoptosis-like changes and dead sperm. A greater (P < 0.05) percentage of acrosome integrity in frozen-thawed spermatozoa was observed in the 60 µM rosiglitazone group. There was no significant difference between 40 and 60 µM rosiglitazone in intact acrosome of ram thawed semen. The result showed that supplementation in ram semen extender with rosiglitazone had a positive role in the regulation of ram sperm motility and had strong protective effect on the sperm membrane and acrosome integrity.

Focal Microscopy Observe the Mechanism of Gegen Qinlian Decoction Treating Type 2 Diabetic Nephropathy in Nude Mice.

The incidence of diabetes is increasing year by year; among them, the rising trend of T2D is particularly obvious, and because it has many complications and poor prognosis, it has become one of the diseases that seriously endanger human health. Gegen Qinlian Decoction (GQD) has achieved good results in the treatment of type 2 diabetes (T2D). It can not only improve the anti-insulin effect of nude mice with type 2 diabetic, but also has the characteristics of small side effects and remarkable curative effect; it can improve the function of tissues and organs by multiple target spots and multiple ways. The method was to raise 30 nude mice with high fat and high sugar and inject small doses of streptozotocin (STZ). The treated nude mice were randomly divided into rosiglitazone group, Gegen Qinlian group, and model group, normally rearing 10 nude mice as a control group. The model group and the blank group were treated with 0.9% sodium chloride solution at 10 mL/kg, and the rosiglitazone group was intragastric administration with 3 mg/kg rosiglitazone solution. The GQD group was treated with 18.2 g/kg GQD, once a day, and lasting for 4 weeks. Use blood glucose meter to detect the FBG content in nude mice, use the radioimmunoassay to detect the amount of FINS, and calculate HOMA-IR. Use immunoenzyme linked assay method to detect the level of serum inflammatory factors. The experimental results showed that compared with the model group, the FBG of the rosiglitazone group mice was significantly decreased; the levels of the rosiglitazone group and the Gegen Qinlian group were significantly lower. Therefore, it is concluded that GQD can treat T2D in nude mice.

HM-Chromanone Ameliorates Hyperglycemia and Dyslipidemia in Type 2 Diabetic Mice.

The effects of (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HMC) on hyperglycemia and dyslipidemia were investigated in diabetic mice. Mice were separated into three groups: db/db, rosiglitazone and HMC. Blood glucose or glycosylated hemoglobin values in HMC-treated mice were significantly lower compared to db/db mice. Total cholesterol, LDL-cholesterol, and triglyceride values were lower, and HDL-C levels were higher, in the HMC group compared to the diabetic and rosiglitazone groups. HMC markedly increased IRS-1Tyr612, AktSer473 and PI3K levels and plasma membrane GLUT4 levels in skeletal muscle, suggesting improved insulin resistance. HMC also significantly stimulated AMPKThr172 and PPARα in the liver, and ameliorated dyslipidemia by inhibiting SREBP-1c and FAS. Consequently, HMC reduced hyperglycemia by improving the expression of insulin-resistance-related genes and improved dyslipidemia by regulating fatty acid synthase and oxidation-related genes in db/db mice. Therefore, HMC could ameliorate hyperglycemia and dyslipidemia in type 2 diabetic mice.

Rosiglitazone ameliorates acute hepatic injury via activating the Nrf2 signaling pathway and inhibiting activation of the NLRP3 inflammasome.

Acute hepatic injury is a common liver disease in clinical practice. Drugs with antioxidant activity exhibit a great potential for alleviating liver injury. The present study aimed to explore the role of rosiglitazone (RSG), a previously reported compound with anti-inflammatory properties, in hepatic injury. Kunming mice were divided into the following four groups: The control group; the RSG group; the carbon tetrachloride (CCl4) group; and the RSG + CCl4 group. Hepatic injury was confirmed by histological examination of the liver. In addition, the serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and those of the biochemical indices superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), NO and reactive oxygen species (ROS) were measured in each group of mice. Additionally, the levels of inflammatory factors and apoptosis-related proteins, as well as the activity of the related signaling pathways, were evaluated. The results showed that RSG could reverse the CCl4-mediated decrease in the levels of SOD, CAT and GSH, and increase in the levels of ALT, AST, MDA, NO and ROS. Furthermore, treatment with RSG could reduce the expression levels of inflammation- and apoptosis-related proteins, thus suggesting that RSG could attenuate inflammation and liver cell apoptosis. Additionally, treatment with RSG promoted the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, upregulated peroxisome proliferator-activated receptor γ and inhibited activation of the inflammasome NOD-like receptor protein 3 (NLRP3). In conclusion, the current study demonstrated that RSG could ameliorate acute hepatic injury via activating the Nrf2 signaling pathway and inhibiting activation of the NLRP3 inflammasome. The findings of the present study partly uncovered the mechanism underlying the effect of RSG on hepatic injury, thus supporting the application of RSG in clinical practice.

Effects of alcohol extract of radish seed on blood lipid, glucose and liver steatosis in ApoE-/- mice

Objective: To investigate the effects and mechanisms of alcohol extract of Raphani seed (AERS) on blood lipid, blood glucose and hepatic steatosis in ApoE-/- mice. Methods: Sixty ApoE-/- mice were randomly divided into control group (CG), normal saline group (NG), rosiglitazone group (RG) and AERS treatment groups (AERS-L / M / H). Except CG, other groups were fed with high-fat, high-sugar and high-salt diet for 9 weeks. The mice in RG were treated with rosiglitazone (1.33 mg·kg-1, 0.2 ml ·10 g-1) by gavage daily. The mice in CG and NG were treated with equal volume of NS by intragastric administration daily. The mice in AERS groups were treated with AERS at the doses of 100, 300 and 900 mg·kg-1 for 9 weeks, respectively. FPG and Fins were detected. Insulin resistance index (IRI) and liver coefficient (LC) were calculated. The levels of ALT, AST, Leptin (LEP), TNF - α and blood lipid (TC, FFA, etc.) were tested. The expressions of proteins related to liver lipid metabolism (HMG-R、LDL-R、LEP-R) were detected by Western blot. Results: Compared with NG or RG, CG showed significant changes in liver appearance (color, swelling, etc.) and pathology (steatosis, hepatocyte necrosis, etc.), while AERS-M/H groups were similar to CG. Compared with CG, the serum levels of FPG, Fins, IRI, ALT, AST, TNF-α, LC, TG, LDL-C, FFA and LEP were increased significantly (P＜0.05) . Compared with NG, AERS could decrease the above mentioned indicators in a dose-dependent manner (P＜0.05). Compared with RG, the levels of FPG and Fins of AERS-H were increased significantly, while the level of IRI was decreased (P＜0.05). Compared with NG and RG, the protein expressions of HMG-R and LEP-R in AERS groups were decreased, while the protein expression of LDL-R was increased in a dose-dependent manner (P＜0.05). Conclusion: AERS can prevent the increase of blood lipid, glucose and hepatic steatosis induced by high-fat and high-sugar diet in ApoE-/- mice. The mechanism is related to the decrease of FFA and LEP, the inhibition of TNF-α, HMG-R, LEP-R protein expressions and the promotion of LDL-R protein expression.

Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.

Effect of metformin and rosiglitazone in non-obese polycystic ovary syndrome women with insulin resistance

Objective: To investigate effects of metformin and rosiglitazone in non-obese polycystic ovary syndrome (PCOS) women with insulin resistance. Methods: Totally 200 non-obese PCOS women with insulin resistance in West China Second Hospital of Sichuan University were enrolled into this study from Sep. 2013 to Jun. 2016, and were randomly divided into two treatment groups: metformin group (1 500 mg/d) and rosiglitazone group (4 mg/d). The treatment lasted for 6 months. Their clinical and biochemical parameters were collected and compared. Results: In both groups, menstrual cycles [metformin group (37±4) days, rosiglitazone group (35±4) days] were shorter after treatment for 6 months (both P<0.01). After treatment for 6 months, body mass index [metformin group (21.6±1.6) kg/m2, rosiglitazone group (21.7±1.7) kg/m2] decreased in both groups (both P<0.01); decreased LH/FSH ratio (metformin group 1.67±0.80, rosiglitazone group 1.70±0.83) was also observed (both P<0.05). After treatment for 6 months, fasting insulin level [metformin group (13.5±5.1) mU/L, rosiglitazone group (12.7±5.6) mU/L] and homeostasis model assessment-insulin resistance index (metformin group 3.0±1.2, rosiglitazone group 2.8±1.2) were decreased in both groups (all P<0.01). Conclusions: For non-obese PCOS insulin resistance patients, screening of anthropometric and metabolic parameters is necessary. For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.

Rosiglitazone alleviates lipopolysaccharide-induced inflammation in RAW264.7 cells via inhibition of NF-κB and in a PPARγ-dependent manner.

Rosiglitazone is a synthetic peroxisome proliferator-activated receptor (PPAR)γ agonist widely used for the treatment of type 2 diabetes. Recent studies have demonstrated that rosiglitazone displays anti-inflammatory effects. The present study aimed to investigate whether rosiglitazone alleviates decreases in RAW264.7 cell viability resulting from lipopolysaccharide (LPS)-induced inflammation, as well as exploring the underlying mechanism. A macrophage inflammatory injury model was established by treating RAW264.7 cells with 100 ng/ml LPS. Cells were divided into LPS and rosiglitazone groups with different concentrations. Cell viability was assessed by performing an MTT assay. The expression of inflammatory cytokines was detected by conducting enzyme-linked immunosorbent assays and reverse transcription-quantitative PCR. Nitric oxidesecretion was assessed using the Griess reagent system. The expression levels of key nuclear factor-κB pathway-associated proteins were detected via western blotting. Rosiglitazone alleviated LPS-induced decrease in RAW264.7 cell viability and inhibited inflammatory cytokine expression in a concentration-dependent manner. Rosiglitazone significantly inhibited LPS-induced upregulation of p65 phosphorylation levels and downregulated IκBα expression levels. However, rosiglitazone-mediated inhibitory effects were reversed by PPARγ knockdown. The results of the present study demonstrated that rosiglitazone significantly inhibited LPS-induced inflammatory responses in RAW264.7 macrophage cells, which was dependent on PPARγ activation and NF-κB suppression.

The Effect of Diabetes Mellitus, Insulin, and Thiazolidinediones on Bone Histomorphometry in Streptozotocin-induced Diabetic Postmenopausal Wistar Rats

Background: Osteoporosis is a metabolic skeletal disease with low bone mass and bone microarchitectural disorganization. Thiazolidinediones (TZD) increase insulin sensitivity through activation of peroxisome proliferator-activated receptor gamma (PPARγ). One of the most important side effects of this drugs is its effects on bone, especially in postmenopausal women. The purpose of this study was to evaluate the effect of diabetes mellitus (DM), insulin, and TZDs on bone in postmenopausal Wistar rats.&#x0D; Methods: Sixteen postmenopausal Wistar rats were divided into four groups: (i) control group, (ii) Streptozotocin-induced DM group without treatment, (iii) Streptozotocin-induced DM group with insulin therapy, and (iv) Streptozotocin-induced DM group receiving rosiglitazone. Pictures of the obtained samples were taken under computer-equipped photo-light microscope, and bone tissue ratios were calculated in an area of 1 mm2. In this area, trabecular thicknesses were measured from six randomly selected regions. In addition, femoral neck regions were determined by measuring the farthest distance.&#x0D; Results: Compared to the control group, trabecular thicknesses were decreased in the uncontrolled DM and rosiglitazone groups. In the rosiglitazone-treated group, trabecular thickness was decreased compared to the uncontrolled DM group. The histological examination of the bones showed that uncontrolled DM and rosiglitazone treatment negatively affected the osteoblast and osteocyte activity. Insulin-treated group had a similar histologic examination compared to the control group.&#x0D; Conclusion: Our study showed that DM had unfavorable effects on bones, and rosiglitazone further exerts this effect. However, the negative effect of DM may be neutralized with the use of insulin.&#x0D; Keywords: diabetes mellitus, bone, osteoporosis, bone histomorphometry, rosiglitazone, insulin, thiazolidinediones

Effects of rosiglitazone on growth and skeletal muscle glucose metabolism of GIFT tilapia based on PI3K/Akt signaling pathway

This study aimed to investigate the effects of rosiglitazone on glucose metabolism of GIFT tilapia based on the PI3K/Akt signalling pathway. The experiment was divided into five groups: normal starch group (32%, LC), high starch group (53%, HC), HC + rosiglitazone group 1 (10 mg/kg, R1), HC + rosiglitazone group 2 (20 mg/kg, R2) and HC + rosiglitazone group 3 (30 mg/kg, R3). The results showed that a high starch diet added with 10–20 mg/kg rosiglitazone had a better specific growth rate and protein efficiency that was beneficial for the growth of the tilapia. With an increase in the rosiglitazone concentration, the contents of serum glucose, insulin and hepatic glycogen in the R1, R2 and R3 groups decreased gradually. Meanwhile, the muscle glycogen content in the R1, R2 and R3 groups increased gradually. The mRNA expression of the IRS-1, PI3K, GLUT-4 and Akt proteins in the R1, R2 and R3 groups was significantly higher than that in the HC group (p < 0.05). Compared with the HC group, the expression of the GSK-3 mRNA in the R1, R2 and R3 groups was significantly reduced (p < 0.05). The protein expression of p-GSK-3β (phosphorylated GSK-3β) in the R1 and R2 groups was significantly higher than that in the HC group (p < 0.05). In conclusion, a high starch diet supplemented with rosiglitazone can improve growth, enhanced the serum biochemical indices and increase the muscle glycogen content in the GIFT tilapia. It benefits in upregulating the IRS-1, PI3K and GLUT-4 mRNA in the skeletal muscle and promotes glucose uptake. Meanwhile, the phosphorylation of Akt and GSK-3β increased significantly and resulted in the inactivation of GSK-3β and alleviation of insulin resistance. Under these experimental conditions, the optimal dosage of rosiglitazone on tilapia was 10–20 mg/kg diet.