Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.738
Filtrar
1.
Contrast Media Mol Imaging ; 2022: 1888153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072636

RESUMO

As one of the common complications of diabetes mellitus (DM), Diabetic Peripheral Neuropathy (DPN) threatens human lives seriously. Emerging evidences have confirmed the protective effects of lidocaine on DPN. However, the possible role and underlying mechanisms of lidocaine in DPN have not been clarified. In this study, the potential role of lidocaine in DPN is explored, and the possible mechanisms are investigated. The rat DPN model is constructed through administration of streptozotocin (STZ, 60 mg/kg). All rats are randomly divided into four groups, including the control group, DPN group, lidocaine (3.78 mg/time) group, and lidocaine combined with the SP600125 (15 mg/kg) group. Mechanical threshold, thermal latency, and blood glucose of rats before and after treatment are detected, and Nerve Conduction Velocity (NCV) is assessed. Moreover, qRT-PCR and western blot assays are carried out to determine the expressions of the c-Jun signaling pathway. The experimental results demonstrate that lidocaine remarkably downregulates the mRNA and protein expressions of the c-Jun signaling pathway in serum and DRGs induced with DPN. Besides, lidocaine combined with SP600125 can obtain better effects than lidocaine alone. It is clearly evident that lidocaine has a certain therapeutic effect on DPN.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Humanos , Lidocaína/farmacologia , Lidocaína/uso terapêutico , NAD/metabolismo , NAD/uso terapêutico , Ratos , Transdução de Sinais , Estreptozocina/uso terapêutico
2.
Biomed Res Int ; 2022: 4469766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046447

RESUMO

Background: Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods: Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results: In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1ß. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion: Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas , Osteoporose , Animais , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Osteoporose/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina
3.
Biomed Pharmacother ; 153: 113424, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076545

RESUMO

Diabetic nephropathy (DN) is one of the most serious microvascular complications following diabetes mellitus (DM). Ferulic acid (FA), a phenolic acid widely found in plants, has multiple pharmacological effects such as anti-oxidation, anti-inflammation and anti-tumor. However, the current research on FA in the field of DN is insufficient. The present study aimed to explore the nephroprotective effect of FA on DN in mice and reveal its underlying mechanism. DN was induced by high-fat diet (HFD) combined with streptozotocin (STZ) injection in male C57BL/6J mice. Animals were randomly divided into four groups (n = 8): Control group, DN group, FA group (200 mg/kg FA, i.g.) and valsartan (VAL) group (12 mg/kg VAL, i.g.). The drug was administered once a day for 8 weeks. Treated with FA, the body weight and fasting blood glucose (FBG) of DN mice were reduced and the renal organ coefficient was significantly optimized. Meanwhile, FA decreased levels of 24-h urine protein excretion (24-h UP) in urine and blood urea nitrogen (BUN), creatinine (Cr) in serum, reduced levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in serum. In addition, FA promoted light chain 3 (LC3) expression markedly, and inhibited the expressions of p62, NOD-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-1ß (IL-1ß) in renal tissues. In conclusion, FA played a positive role in alleviating renal injury in HFD/STZ-induced DN mice by enhancing autophagy and suppressing excessive inflammation.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Autofagia , Colesterol/metabolismo , Ácidos Cumáricos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Inflamação/metabolismo , Rim , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina/farmacologia
4.
Biomed Pharmacother ; 153: 113510, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076597

RESUMO

Balanites aeqyptiaca (BA) seeds were toasted at 70 °C, milled and the oil expelled to resolve to meal which were defatted to resolve to defatted balanites aeqyptiaca (BA) protein meal and (BA) protein concentrate respectively. These were subjected to analysis using standard methods. There exist marked trend between defatted balanites aeqyptiaca protein meal, protein concentrate and incidences of diabetes. This work investigated the anti- diabetic effects of balanites aeqyptiaca defatted protein meal and concentrate supplemented diets in streptozotocin (STZ)-induced diabetic rats. The rats were fattened for two weeks with high fat diet (HFD) to introduce Hyperglycemia and then made diabetic by intraperitoneal administration of STZ (35 mg/kg body weight) and fed diets containing 5 % defatted balanites aeqyptiaca protein meal (DAPM) and 5 % balanites aeqyptiaca protein concentrate (APC) for 14 days. The effect of the diet on blood glucose, serum glutathione peroxidase (GPx), glutathione transferase (GSH), thiobarbituric acid reactive species (TBARS), α-amylase and intestinal α-glucosidase activities were investigated. There was marked increase in the blood glucose, TBARS, pancreatic α-amylase and intestinal α-glycosidase with corresponding decrease in serum GPx and GSH contents in diabetic rats control groups. These trends were however, reversed in diabetic rats fed diet supplemented with the balanites aeqyptiaca protein meals for 14 days. The meals from defatted and protein concentrate inhibit α-amylase and α-glycosidase inhibitory activity in vivo. Thus, the anti-diabetes properties of the defatted meal and protein concentrate may be attributed to the influence of its constituent phytochemicals on starch digestion as well as endogenous enzymes activities. The study revealed that defatted aduwa meal and proteins concnentrate demonstrated potentials used as functional ingredients in food materials and could also increase income access of low resource populace.


Assuntos
Balanites , Diabetes Mellitus Experimental , Animais , Balanites/química , Glicemia/metabolismo , Dieta , Glutationa Peroxidase/metabolismo , Hipoglicemiantes/farmacologia , Refeições , Ratos , Ratos Wistar , Estreptozocina , Substâncias Reativas com Ácido Tiobarbitúrico/análise , alfa-Amilases/metabolismo
5.
Biomed Pharmacother ; 153: 113533, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076612

RESUMO

Oxidative stress, a key player in diabetic retinopathy (DR), is associated with retinal cell apoptosis. This study investigated the effect of tocotrienol-rich fraction (TRF), a potent antioxidant, towards visual behaviour, retinal morphology, cells apoptosis and redox status in streptozotocin (STZ)-induced DR rats. Sprague-Dawley rats were divided into 3 groups: non-diabetic (N), was injected with citrate buffer intraperitoneally, diabetic treated with vehicle (DV), and diabetic treated with TRF (DT), were injected with STZ intraperitoneally (55 mg/kg) to induce diabetes. DT received 100 mg of TRF/kg orally for 12-weeks, whereas DV and N received vehicle. The general and visual-behaviour responses were assessed at week 12 in an open field arena. Rats were then sacrificed, and retinae were processed for haematoxylin and eosin (H&E) and terminal transferase-mediated dUTP nick end-labelling (TUNEL) staining. Retinal antioxidant, lipid peroxidation and anti-apoptotic markers were measured. The general and visual-behaviour responses in DT were comparable to N. Retinal thickness and cell counts were lower in DV and DT compared to N. Lower number of TUNEL-positive cells were observed in DT compared to DV (1.48-fold, p < 0.001) which correlated with retinal caspase-3 expression (2.31-fold, p < 0.001). The retinal oxidative stress in DT was lower than DV as indicated by higher reduced glutathione (2.10-fold, p < 0.05), superoxide dismutase (1.12-fold, p < 0.05) and catalase (1.40-fold, p < 0.001), and lower malondialdehyde (2.54-fold, p < 0.001). In conclusion, oral TRF (100 mg/kg) supplementation for 12-weeks reduces retinal oxidative stress in STZ-induced DR rats, which in turn reduces retinal cell apoptosis and protects retinal morphology. These findings were associated with preservation of the visual-behaviour responses.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Tocotrienóis , Animais , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Estreptozocina/farmacologia , Superóxido Dismutase/metabolismo , Tocotrienóis/farmacologia , Tocotrienóis/uso terapêutico
6.
Front Endocrinol (Lausanne) ; 13: 942549, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120443

RESUMO

Persistent chronic oxidative stress is a primary pathogenic characteristics of diabetic foot ulcers. Puffball spores are a traditional Chinese medicine used to treat diabetic foot ulcers infections and bedsores. However, their effects against diabetic wounds and the mechanism underlying these effects remain largely unknown. The present study explored the effectiveness of puffball spores in diabetic wound treatment and the mechanisms underlying their effects. Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes were treated with puffball spores to ascertain whether they accelerated wound healing.Real-time quantitative PCR, western blotting, hematoxylin-eosin and Masson's trichrome staining, immunohistochemistry analysis, and immunofluorescence assays were performed. As indicated by wound and serum histology and biochemical analyses, the puffball spores accelerated wound healing by activating Akt/Nrf2 signaling and promoting the expression of its downstream antioxidant genes, markedly stimulating antioxidant activity and enhanceing angiogenesis and collagen deposition. Our findings showed that puffball spores could accelerate diabetic wound healing, enhance antioxidant ability, promote the expression of vascular markers, and suppress inflammation, thus providing a theoretical basis for the treatment of diabetic and refractory wounds.


Assuntos
Diabetes Mellitus Experimental , Pé Diabético , Animais , Antioxidantes/farmacologia , Colágeno/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/terapia , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Fator 2 Relacionado a NF-E2 , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley , Esporos/metabolismo , Estreptozocina , Cicatrização
7.
Molecules ; 27(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36080407

RESUMO

The absence of a treatment efficient in the control of type 2 diabetes mellitus requires more functional products to assist treatment. Luteolin (LU) and diosmin (DIO) have been known as bioactive molecules with potential for the treatment of diabetes. This work aimed to establish the role that a combination of LU and DIO in selenium nanoparticles (SeNPs) played in streptozotocin (STZ)- induced diabetes mice. Green synthesis of Se NPs was performed by mixing luteolin and diosmin with the solution of Na2SeO3 under continuous stirring conditions resulting in the flavonoids conjugated with SeNPs. The existence of flavonoids on the surface of SeNPs was confirmed by UV-Vis spectra, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) images, and DLS graphs via Zetasizer. The average diameter of GA/LU/DIO-SeNPs was 47.84 nm with a PDI of -0.208, a zeta potential value of -17.6, a Se content of 21.5% with an encapsulation efficiency of flavonoids of 86.1%, and can be stabilized by gum Arabic for approximately 175 days without any aggregation and precipitation observed at this time. Furthermore, The C57BL/6 mice were treated with STZ induced-diabetes and were exposed to LU/DIO, SeNPs, and GA/LU/DIO-SeNPs for six weeks. The treatment by nanospheres (GA/LU/DIO-SeNPs) in the mice with diabetes for a period of 6 weeks restored their blood glucose, lipid profile, glycogen, glycosylated hemoglobin, and insulin levels. At the same time, there were significant changes in body weight, food intake, and water intake compared with the STZ- untreated induced diabetic mice. Moreover, the GA/LU/DIO-SeNPs showed good antioxidant activity examined by catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) in liver and kidney and can prevent the damage in the liver evaluated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. The nanospheres exhibited a significant anti-diabetic activity with a synergistic effect between the selenium and flavonoids. This investigation provides novel SeNPs nanospheres prepared by a high-efficiency strategy for incorporating luteolin and diosmin to improve the efficiency in type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Diosmina , Nanopartículas , Selênio , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Luteolina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Selênio/química , Estreptozocina
8.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36077157

RESUMO

Sexual dysfunction is a common problem for men with diabetes. Epigallocatechin gallate (EGCG) is known to ameliorate erectile function in aging rats. However, there has not yet been a report to evaluate its effects on diabetic male rat sexual behavior in the literature. In this study, we investigated the effects of EGCG on male sexual behavior in diabetic rats. Diabetic rats were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin. After streptozotocin injection for one week, animals were then orally treated with 40 mg/kg of EGCG or vehicle. Copulatory behavior and fasting blood glucose levels were recorded before treatment, as well as 7 and 14 days after treatment. Serum LH, testosterone, and PDE5a levels were measured by EIA assay after the last behavioral test. Data showed that diabetic rats who had diminished sexual functions demonstrated significantly increased latencies in mount, intromission, and ejaculation, as well as significant decreases in frequencies of intromission and ejaculation, compared to non-diabetic controls, indicating sexual function recovery. Lower blood glucose levels were also found in diabetic rats after EGCG treatment. Additionally, the lower LH and higher PDE5a levels in diabetic rats than controls were also noted. The findings declared that EGCG had a protective effect on male sexual behavior in diabetic rats.


Assuntos
Catequina , Diabetes Mellitus Experimental , Animais , Glicemia , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Masculino , Ratos , Estreptozocina
9.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077238

RESUMO

Patients with diabetes mellitus tend to develop ischemia-related complications and have compromised endothelial progenitor cell (EPC) function. Melatonin protects against ischemic injury, possibly via EPC modulation. We investigated whether melatonin pretreatment could restore EPC function impairment and improve circulation recovery in a diabetic critical limb ischemia mouse model. Under 25 mM high-glucose medium in vitro, EPC proliferation, nitric oxide production, tube formation, and endothelial nitric oxide synthase (eNOS) phosphorylation were significantly suppressed. Hyperglycemia promoted EPC senescence and apoptosis as well as increased reactive oxygen species (ROS) production. Melatonin treatment reversed the harmful effects of hyperglycemia on EPC through adenosine monophosphate-activated protein kinase-related mechanisms to increase eNOS phosphorylation and heme oxygenase-1 expression. In an in-vivo study, after a 4-week surgical induction of hindlimb ischemia, mice with streptozotocin (STZ)-induced diabetes showed significant reductions in new vessel formation, tissue reperfusion, and EPC mobilization in ischemic hindlimbs compared to non-diabetic mice. Mice with STZ-induced diabetes that received melatonin treatment (10 mg/kg/day, intraperitoneal) had significantly improved blood perfusion ratios of ischemic to non-ischemic limb, EPC mobilization, and densities of capillaries. In addition, a murine bone marrow transplantation model to support these findings demonstrated that melatonin stimulated bone marrow-originated EPCs to differentiate into vascular endothelial cells in femoral ligation-induced ischemic muscles. In summary, this study suggests that melatonin treatment augments EPC function along with neovascularization in response to ischemia in diabetic mice. We illustrated the protective effects of melatonin on EPC H2O2 production, senescence, and migration through melatonin receptors and modulating eNOS, AMPK, and HO-1 activities at the cellular level. Thus, melatonin might be used to treat the impairment of EPC mobilization and circulation recuperation in response to ischemic injury caused by chronic hyperglycemia. Additional studies are needed to elucidate the applicability of the results in humans.


Assuntos
Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Hiperglicemia , Melatonina , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Células Progenitoras Endoteliais/metabolismo , Membro Posterior/irrigação sanguínea , Humanos , Peróxido de Hidrogênio/metabolismo , Hiperglicemia/metabolismo , Isquemia/metabolismo , Melatonina/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica , Estreptozocina/farmacologia
10.
PLoS One ; 17(9): e0273703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107823

RESUMO

OBJECTIVE: Numerous methods for modeling gestational diabetes mellitus (GDM) in rats exist. However, their repeatability and stability are unclear. This study aimed to compare the effects of high-fat and high-sugar (HFHS) diet, HFHS diet combined with streptozotocin (STZ) administration, and HFHS diet combined with movement restriction (MR) modeling methods on rat models to confirm the best method for constructing a rat model of GDM. METHOD: Forty female Sprague-Dawley rats were randomly divided into four groups (n = 10): the normal control (NC), HFHS, HFHS+STZ, and HFHS+MR groups. The rats in the NC group were fed with a standard diet, and those in the remaining groups were fed with a HFHS diet. The rats in the HFHS+STZ group received 25 mg/kg STZ on their first day of pregnancy, and those in the HFHS+MR group were subjected to MR during pregnancy. Bodyweight, food intake, water intake, fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of insulin sensitivity (HOMA-IS), homeostasis model assessment of ß-cell function, pancreatic and placental morphology, and the expression levels of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in placentas were then quantified. Moreover, iTRAQ was used to identify placental proteomics. RESULTS: During pregnancy, the rats in the HFHS+STZ group showed FBG levels that were kept stable in a state of moderate hyperglycemia; the typical GDM symptoms of polydipsia, polyphagia, polyuria, and increased body weight; and the modeling rate of 87.5%. On the first and 19th days of pregnancy, the rats in the HFHS group showed higher FBG than that of the NC group, increasing body weight and food intake and the modeling rate of 50%. On the 19th day of pregnancy, the FBG of the rats in the HFHS+MR group was higher than that of the rats in the NC group, and the modeling rate of 42.9%. Comparison with the NC group revealed that the three modeling groups exhibited increased FINS and HOMA-IR, decreased HOMA-IS, and different degrees of pathological changes in pancreases and placentas. Among the groups, the HFHS+STZ group displayed the greatest changes with significant reductions in the numbers of pancreatic and placental cells and appeared cavitation. The expression levels of GLUT1 and GLUT3 in the placentas of the HFHS+STZ and HFHS+MR groups were higher than those in the placentas of the NC and HFHS groups. The above results indicated that the rats in the HFHS+STZ group showed the best performance in terms of modeling indicators. After the changes in placental proteomics in the HFHS+STZ group were compared with those in the NC group, we found that in the HFHS+STZ group, five proteins were up-regulated and 18 were down-regulated; these proteins were enriched in estrogen signaling pathways. CONCLUSION: HFHS combined with the intraperitoneal injection of 25 mg/kg STZ was the best modeling method for the nonspontaneous model of experimentally induced GDM, and its modeling rate was high. The pathological characteristics of the constructed GDM rat model were similar to those of human patients with GDM. Moreover, the model was stable and reliable. The modeling method can provide a basis for constructing a GDM rat model for subsequent research on the prevention and treatment of GDM.


Assuntos
Diabetes Gestacional , Animais , Glicemia , Peso Corporal , Diabetes Gestacional/metabolismo , Estrogênios , Feminino , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 3 , Humanos , Insulina/metabolismo , Placenta/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Estreptozocina
11.
Iran J Med Sci ; 47(5): 484-493, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36117578

RESUMO

Background: Brown algae have gained worldwide attention due to their significant biological activities, such as antidiabetic properties. In the present study, the antidiabetic properties of six brown algae from the Persian Gulf were investigated. Methods: An experimental study was conducted from 2017 to 2019 to examine the inhibitory effects of six brown algae against the α-glucosidase activity. Methanol (MeOH) and 80% MeOH extracts of Colpomenia sinuosa, Sargassum acinaciforme, Iyengaria stellata, Sirophysalis trinodis, and two accessions of Polycladia myrica were analyzed. The effect of 80% MeOH extracts of Sirophysalis trinodis on blood glucose levels in streptozotocin-induced diabetic rats was evaluated. Chemical constituents of brown algae were analyzed using thin-layer chromatography and liquid chromatography-mass spectrometry techniques. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The 80% MeOH extracts of Iyengaria stellata (IC50=0.33±0.15 µg/mL) and Colpomenia sinuosa (IC50=3.50±0.75 µg/mL) as well as the MeOH extracts of Colpomenia sinuosa (IC50=3.31±0.44 µg/mL) exhibited stronger inhibitory effect on α-glucosidase than the acarbose (IC50=160.15±27.52 µg/mL, P<0.001). The 80% MeOH extracts of Sirophysalis trinodis reduced postprandial blood glucose levels in diabetic rats compared to the control group (P=0.037). Fucoxanthin was characterized as the major antidiabetic agent in most of the algal extracts. Conclusion: Sirophysalis trinodis is recommended as a novel source for isolation and identification of potential antidiabetic compounds due to its high in vivo and in vitro antidiabetic effects.


Assuntos
Diabetes Mellitus Experimental , Feófitas , Acarbose , Animais , Glicemia/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Oceano Índico , Metanol , Feófitas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Estreptozocina/análise , alfa-Glucosidases
12.
Front Endocrinol (Lausanne) ; 13: 926129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082077

RESUMO

Aims/Objectives: Wound healing in people with diabetes is delayed secondary to impaired nitric oxide generation, advanced glycation end products (AGE), and poor migration of epithelial cells. We developed a novel topical esmolol hydrochloride (Galnobax) and assessed its efficacy for wound healing in streptozocin-induced diabetic hairless rat. Methods: All experiments were performed at an animal laboratory and tertiary-care research facility. Ex vivo aldose reductase inhibition was assessed from enzymes obtained from a bacterial culture (spectrophotometer), sorbitol content in homogenized red blood cells, and AGE in glucose and bovine serum by fluorometry following the addition of esmolol in varying concentrations. A scratch assay of human fibroblasts, endothelial cells, and keratinocytes was assessed under a high-glucose environment and after esmolol by phase-contrast microscopy. The efficacy evaluation of the topical application of Galnobax (14 and 20%) or vehicle was conducted in streptozotocin-induced diabetic hairless rats, and endogenous nitrite and hydroxyproline from homogenized wound tissue were measured along with pharmacokinetic and dermal toxicity in Hanford miniature swine. Results: Esmolol inhibited the formation of sorbitol by 59% in erythrocytes in comparison to glucose-induced sorbitol levels. AGE generation in bovine serum albumin was reduced at 1 mM esmolol concentrations (2.6 ± 1.7) compared with control (p < 0.05) and similar to that of diclofenac (2.5 ± 1.3). Esmolol at 1 and 10 µM enhanced the migration of fibroblasts, epithelial cells, and keratinocytes compared with control. The nitric oxide levels (day 7) were 44 and 112% higher with Galnobax (14%) than those of the diabetic group (p < 0.05) and the vehicle control group (p < 0.05), respectively. The days 7 and 14 hydroxyproline in the wound was higher by 22 and 44% following Galnobax (14%) compared with the diabetic and vehicle control groups. The wound area exhibited better reduction with Galnobax at 14% up to day 10 follow-up compared with the controls. The pharmacokinetic and dermal toxicity in miniature swine suggested no significant adverse event with Galnobax. Conclusions: Topical esmolol hydrochloride is a novel, safe, and effective treatment modality that acts through pleotropic mechanisms to hasten wound healing in diabetes.


Assuntos
Diabetes Mellitus , Produtos Finais de Glicação Avançada , Aldeído Redutase/farmacologia , Animais , Células Endoteliais , Fibroblastos , Glucose/farmacologia , Humanos , Hidroxiprolina/farmacologia , Óxido Nítrico/farmacologia , Propanolaminas , Ratos , Sorbitol/farmacologia , Estreptozocina , Suínos , Porco Miniatura , Cicatrização
13.
Pharm Biol ; 60(1): 1732-1738, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36086879

RESUMO

CONTEXT: Salidroside (SAL), one of the major glycosides isolated from the roots of Rhodiola rosea L. (Crassulaceae), has anti-inflammatory, antioxidant, and antidiabetic properties. OBJECTIVE: Our study assessed whether SAL exerts a protective effect on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via the Akt/GSK-3ß signalling pathway. MATERIALS AND METHODS: Adult male Wistar rats were divided into three groups (n = 8): normal control, DN + vehicle, and DN + SAL. SAL (50 mg/kg/day, oral) was administered for 8 weeks. Biochemical and histopathologic examinations were performed to evaluate the therapeutic effects of SAL on oxidative stress, inflammation, renal function, and apoptosis. RESULTS: SAL induced rats demonstrated ameliorated levels of FBG (20.53 ± 0.72 mmol/L vs. 26.02 ± 1.44 mmol/L), urine albumin excretion (27.00 ± 1.46 mmol/L vs. 41.00 ± 1.59 mmol/L), blood urea nitrogen (14.42 ± 0.70 mmol/L vs. 17.77 ± 0.72 mmol/L), and serum creatinine (112.80 ± 6.98 mmol/L vs. 159.00 ± 3.81 mmol/L) compared to normal control rats, along with the alleviation of renal pathologic changes by improving the irregular shape of glomeruli tissues. Biochemical analysis showed that SAL-treated animals displayed suppressed levels of serum inflammatory cytokines and kidney oxidative stress markers and attenuated apoptotic characteristics. Moreover, it increased the phosphorylation levels of Akt and GSK-3ß in kidneys. DISCUSSION AND CONCLUSION: The present study validated the involvement of the Akt/GSK-3ß signalling pathway in renal improvement. These findings can form the basis to investigate the protective effect of SAL in DN in clinical trials.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/prevenção & controle , Glucosídeos , Glicogênio Sintase Quinase 3 beta/metabolismo , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Masculino , Estresse Oxidativo , Fenóis , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Estreptozocina/farmacologia
14.
Sci Data ; 9(1): 558, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088402

RESUMO

Mouse models for streptozotocin (STZ) induced diabetes probably represent the most widely used systems for preclinical diabetes research, owing to the compound's toxic effect on pancreatic ß-cells. However, a comprehensive view of pancreatic ß-cell mass distribution subject to STZ administration is lacking. Previous assessments have largely relied on the extrapolation of stereological sections, which provide limited 3D-spatial and quantitative information. This data descriptor presents multiple ex vivo tomographic optical image datasets of the full ß-cell mass distribution in mice subject to single high and multiple low doses of STZ administration, and in glycaemia recovered mice. The data further include information about structural features, such as individual islet ß-cell volumes, spatial coordinates, and shape as well as signal intensities for both insulin and GLUT2. Together, they provide the most comprehensive anatomical record of the effects of STZ administration on the islet of Langerhans in mice. As such, this data descriptor may serve as reference material to facilitate the planning, use and (re)interpretation of this widely used disease model.


Assuntos
Diabetes Mellitus Experimental , Ilhotas Pancreáticas , Animais , Glicemia/análise , Insulina/análise , Camundongos , Estreptozocina/análise
15.
Nutrients ; 14(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36079819

RESUMO

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that is characterized by hyperglycemia, insulin resistance, and lack of insulin production. It has been previously reported that Thymus serpyllum has therapeutic potential against many diseases. To investigate the antidiabetic action of Thymus serpyllum, this study aimed to analyze its restorative impact in diabetic mice, in which it was administered in diet. Diabetes was induced in BALB/c mice fed with a high-fat diet and two intraperitoneal injections of streptozotocin. With the onset of diabetes, the mice were administered daily with aqueous extract of Thymus serpyllum (500 mg/kg/d and 800 mg/kg/d) for 4 weeks. Body weight and fasting blood glucose levels were measured after every 1 week of the treatment. Subsequently, intraperitoneal glucose tolerance and insulin tolerance tests were conducted. In addition, liver tissue was isolated for assessment in terms of levels of gene expression of the AMPK, IRS1, and GLUT2 gene. Treatment with the aqueous extract of Thymus serpyllum was found to be significantly effective in controlling hyperglycemia and improving glucose and insulin tolerance. Predictable with these impacts, the extract of Thymus serpyllum upregulated the AMPK expression at the mRNA level, as well as upregulating the expression of IRS1 and GLUT2 gene. Histopathological examination of the liver, kidney, and pancreas also revealed the restorative impact in terms of cellular morphology. The results hence demonstrated that oral administration of aqueous extract of Thymus serpyllum can potentially attenuate hyperglycemia in the liver muscle of streptozotocin (STZ)-induced diabetic mice via AMPK and IRS1 upregulation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hiperglicemia , Thymus (Planta) , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Hipoglicemiantes , Insulina , Fígado/metabolismo , Camundongos , Estreptozocina/efeitos adversos , Thymus (Planta)/metabolismo
16.
J UOEH ; 44(3): 287-292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36089347

RESUMO

Pancreatic neuroendocrine carcinoma (NEC) as classified in the World Health Organization (WHO) 2010 was reclassified in the WHO 2017 as either neuroendocrine tumor (NET) G3 or NEC. An accurate diagnosis based on the WHO 2017 classification is important in order treating this disease appropriately. We report a case diagnosed as NET G3 that responded remarkably well to treatment with streptozocin. The patient would likely not have received the streptozocin treatment if she had been diagnosed with NEC. The WHO 2017 classification is reasonable for the treatment of advanced pancreatic neuroendocrine neoplasms.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Feminino , Humanos , Gradação de Tumores , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Estreptozocina/uso terapêutico
17.
Molecules ; 27(16)2022 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-36014421

RESUMO

Alzheimer's disease (AD) is one of the major neurodegenerative disorders, and its incidence increases globally every year. Currently, available AD drugs symptomatically treat AD with multiple adverse effects. Gefitinib (GE) is an epidermal growth factor receptor (EGFR) kinase inhibitor. EGFR is the preferred target for the treatment of AD, whereas the effect of GE in AD conditions is limited. The present study was designed to explore the ameliorative potential of GE in Aß1-42 oligomer-induced neurotoxicity in AD mice. AD was induced by intracerebroventricular (i.c.v.) injection of Aß1-42 oligomer (4 µg/4 µL) into the lateral ventricles of the mouse brain. The test compound, i.e., GE (2 and 4 mg/kg of body weight), was administered orally on days 10, 13, 16, 19, 22, 25, and 28, and the reference drug, i.e., donepezil (DP, 2 mg/kg), was administered orally from the 10th to 28th days. The behavioral changes were screened by the Morris water maze (MWM) test. Furthermore, biomarkers i.e., brain acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels were estimated from brain samples. The AD-associated histopathological changes were analyzed by hematoxylin and eosin staining. The administration of GE significantly ameliorated the AD-associated behavioral, biochemical, and histopathological changes. The ameliorative effect of GE against the Aß1-42 oligomer-associated neurotoxicity was due to its potent inhibition of EGFR kinase activation, as well as its antioxidant and antilipid peroxidative effect.


Assuntos
Doença de Alzheimer , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Receptores ErbB , Aprendizagem em Labirinto , Camundongos , Fragmentos de Peptídeos/farmacologia , Estreptozocina/farmacologia
18.
Nutrients ; 14(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36014875

RESUMO

This study aims to examine the anti-diabetic properties of insoluble and soluble dietary fibers from kiwifruit (KIDF and KSDF) in rats with type 2 diabetes mellitus (T2DM) resulting from a high-fat diet (HFD) and streptozotocin (STZ). Both KIDF and KSDF treatments for four weeks remarkably decreased body weight and increased satiety. In addition, the blood glucose level and circulatory lipopolysaccharide (LPS) content were decreased, while the insulin resistance, inflammatory status, and lipid profiles improved. These anti-diabetic effects might be related to the regulation of gut microbiota and increased SCFA content. The key microbial communities of KIDF and KSDF were different. Furthermore, the KIDF treatment increased the level of total SCFAs and isobutyric acid, while KSDF increased the levels of total SCFAs and butyric acid. The association between critical species and SCFA and between SCFA and biochemical parameters indicated that the mechanisms of KIDF and KSDF on T2DM might be different.


Assuntos
Actinidia , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animais , Ácido Butírico/farmacologia , Dieta Hiperlipídica/efeitos adversos , Fibras na Dieta/farmacologia , Ratos , Estreptozocina
19.
Front Endocrinol (Lausanne) ; 13: 928591, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992111

RESUMO

Background: Hyperglycemia is one of the major risk factors for stroke and stroke recurrence, leading to aggravated neuronal damage after cerebral ischemia/reperfusion (I/R). ERK1/2 signaling pathway plays a vital role in cerebral ischemic injury. However, the role of the ERK1/2 pathway in hyperglycemia-aggravated ischemic brain damage is not clear. Methods: Streptozotocin (STZ; 50 mg/kg)-induced diabetes (blood glucose ≥12 mmol/L) or control groups in adult Sprague-Dawley rats were further subdivided into I/R (carotid artery/vein clamping), I/R + PD98059 (I/R plus ERK1/2 inhibitor), and Sham-operated groups (n = 10 each). Neurobehavioral status (Neurological behavior scores) and the volume of the cerebral infarction (TTC staining); brain mitochondrial potential (JCI ratio test) and cell apoptosis (TUNEL assay); RAS protein expression, phosphorylated/total ERK1/2 and Drp-1 (Dynamic-related protein 1) protein levels (Western blotting); mitochondrial fusion-related proteins mitofusin-1/2 (Mfn1/2), optic atrophy (OPA-1) and mitochondrial fission 1 (Fis1), and autophagy-associated proteins Beclin-1, LC3-I/II and P62 (Western blotting and immunohistochemistry) were analyzed. Results: The I/R + PD98059 group demonstrated better neurobehavior on the 1st (p < 0.05) and the 3rd day (p < 0.01) than the I/R group. Compared to the Sham group, cerebral ischemia/reperfusion brought about neuronal damage in the I/R group (p <0.01). However, treatment with PD98059 showed an improved situation with faster recovery of mitochondrial potential and less apoptosis of neuronal cells in the I/R + PD98059 group (p < 0.01). The I/R group had a higher-level expression of RAS and phosphorylated ERK1/2 and Drp-1 than the diabetes mellitus (DM) group (p < 0.01). The PD98059 treated group showed decreased expression of p-ERK1/2, p-Drp-1, Fis1, and Beclin-1, LC3-I/II and P62, but increased Mfn1/2 and OPA-1 than the I/R group (p < 0.01). Conclusion: Hyperglycemia worsens cerebral ischemia/reperfusion-induced neuronal damage via ERK1/2 activated cell autophagy and mitochondrial fission.


Assuntos
Isquemia Encefálica , Hiperglicemia , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Autofagia , Proteína Beclina-1/metabolismo , Encéfalo/metabolismo , Hiperglicemia/complicações , Sistema de Sinalização das MAP Quinases , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Estreptozocina
20.
Transplantation ; 106(9): 1770-1776, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36001489

RESUMO

BACKGROUND: We previously reported that modified extracellular-type trehalose-containing Kyoto (MK) solution, which contains a trypsin inhibitor (ulinastatin), significantly improved the islet yield compared with University of Wisconsin (UW) preservation, which is the gold standard for organ preservation for islet isolation. In this study, we evaluated the efficiency of a modified histidine-lactobionate (MHL) solution in addition to UW or MK solution. The MHL solution has a high sodium-low potassium composition with low viscosity compared with the UW solution. Moreover, similar to MK solution, MHL solution also contains ulinastatin. METHODS: Porcine pancreata were preserved in UW, MK, or MHL solution, followed by islet isolation. An optimized number (1500 IE) of isolated islets from each group were then transplanted into streptozotocin-induced diabetic mice. RESULTS: The islet yield before and after purification was significantly higher in the MHL group than in the UW group. On the contrary, the islet yield before and after purification was not significantly different between the MHL and MK groups. Preserving the porcine pancreata in MHL solution improved the outcome of islet transplantation in streptozotocin-induced diabetic mice compared with that in UW solution. CONCLUSIONS: Pancreas preservation with MHL solution preserves islet function better than UW solution. The effect of MHL solution is similar to that of MK solution, suggesting that MHL solution can be used as an alternative to MK solution for pancreatic islet transplantation.


Assuntos
Diabetes Mellitus Experimental , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Soluções para Preservação de Órgãos , Adenosina , Alopurinol/farmacologia , Animais , Diabetes Mellitus Experimental/cirurgia , Dissacarídeos , Glutationa/farmacologia , Histidina/farmacologia , Humanos , Insulina/farmacologia , Camundongos , Soluções para Preservação de Órgãos/farmacologia , Pâncreas/cirurgia , Rafinose/farmacologia , Estreptozocina , Suínos , Universidades , Wisconsin
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...