STZ-induced Rats Research Articles

Temuan Baru Ekstrak Kulit Nanas Sebagai Potensi Antidiabetes pada Tikus Putih (Rattus Norvegicus) Diinduksi Streptozotocin

Diabetes mellitus is chronic and metabolic disease which occurs because of the increase of blood glucose level or hyperglycemia caused the body which cannot produce or use insulin effectively. Hyperglycemia has a glucotoxic effect resulting in an increase in ROS (reactive oxygen species) thus inducing liver pathogenesis which promotes severe inflammatory and apoptotic responses, as indicated by an increase in the SGPT enzyme. The pineapple peel contains flavonoid. It is known of having a strong antioxidant activity. With the giving of pineapple peel extract, it is expected to decrease the blood glucose level. This research to find out the the effect of pineapple peel extract (Ananas comusus L. Merr) on decreasing blood glucose levels and SGPT levels in male white rats (Rattus norvegicus) induced by streptozotocin. This research is an experimental study with a research design of pretest and posttest control group design. The samples consisted of 18 rats divided into 6 groups consisted of: normal control, negative control, and positive control group given metformin, and pineapple peel extract with dose 200mg/KgBW, 300mg/KgBW and 500mg/KgBW for 28 days and the measurement of the rats blood glucose was conducted by blood glucose test meter at day 1, day 4 (after post inductionof STZ 45mg/KgBW given by intraperitoneal), and day 29. The analysis result of One Way ANOVA showed that pineapple peel extract with dose 200mg/KgBW, 300mg/KgBW, and 500mg/KgBW decrease the blood glucose level significant (p-value<0,05) with negative control group. There was no significant difference between 200mg/KgBW, 300mg/KgBW and 500mg/KgBW compared with positive control (p>0.05). There was an effect of pineapple peel extract administration on the SGPT levels of STZ-induced rats with a dose of 200mg/kg BW, 300mg/kg BW, 500mg/kg BW (p-value <0.05). The administration of 300mg/kg BW pineapple peel extract had the highest decrease in SGPT levels compared to other groups. Pineapple peel extract (Ananas comosus L. Merr) can reduce blood glucose leveland SGPT levels in rats induced by streptozotocin with the greatest reduction at dose 300mg/KgBW.

The combined effect of morin and hesperidin on memory ability and oxidative/nitrosative stress in a streptozotocin-induced rat model of Alzheimer’s disease

Alzheimer's disease (AD), the most frequent neurodegenerative disease within dementias, affects the CNS, leading to gradual memory issues and cognitive dysfunction. Oxidative stress in AD contributes to ongoing neuronal loss and hastens disease progression. Notably, the potent antioxidant compounds morin and hesperidin have demonstrated significant effectiveness in addressing oxidative stress. This study explores the impact of morin and hesperidin on behavior and oxidative stress in the streptozotocin (STZ)-induced AD rat model. The experiment involved five groups: control, STZ, STZ+morin, STZ+hesperidin, and STZ+morin+hesperidin. The rat model of AD was created by injecting STZ with the stereotaxic surgery. Morin and hesperidin were applied to the groups for 7-days. After the applications, the Morris water maze (MWM) and novel object recognition (NOR) tests were used and the rats were sacrificed. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), and protein carbonyl (PC) levels were measured. In the STZ group, the levels of NOx and PC exhibited a noteworthy increase compared to the control. Conversely, the application of morin and/or hesperidin treatments reduced NOx and PC levels compared to the STZ group. The co-administration of morin and hesperidin improved the antioxidant status and decreased lipid peroxidation in STZ-induced rats. In the STZ group, serum advanced oxidation protein products (AOPP) levels were statistically elevated compared to the control. However, in the treatment groups, morin and/or hesperidin successfully decreased AOPP levels to those observed in the control. The combined use of these flavonoids may have a neuroprotective effect regarding memory problems and decreasing oxidative/nitrosative stress.

Effects of empagliflozin on gonadal functions of hyperglycemic male wistar rats.

Empagliflozin (EMPA) showed antiapoptotic, oxidative and anti-inflammatory potential effect. EMPA attenuates the inflammation and oxidative stress biomarkers in patients with heart failure while significantly decreases the malondialdehyde (a lipid peroxidation marker) levels in the plasma of diabetic patients. The present study examined the effects of moderate hyperglycemia on reproductive function. Sixty male Wister rats ‎ were divided and randomly allocated into four groups of 15 animals each‎‎. Diabetes was induced by a single intraperitoneal injection of a prepared solution containing STZ diluted in 0.1 M sodium citrate buffer (pH 4.5) at a dosage of 40 mg/kg body weight in selected in groups II and III for seven days before starting the treatment with EMPA. The current study revealed that EMPA for eight weeks prevented testicular high glucose-induced oxidative stress markers such as penile nitric oxide (NO), glutathione peroxidase (GPX) and total anti-oxidant capacity (TAC) in STZ-induced hyperglycemia in a rat model. In addition, EMPA ameliorated the high levels of endogenous Interleukin-6 (IL-6) present in gonads in response to an acute inflammatory found in the hyperglycemic STZ-induced rats. The present study further suggested the protective effects of EMPA and how it has a beneficial role and can effectively attenuate hyperglycemia-induced testicular oxidative damage and inflammatory markers as well as androgen dependent testicular enzymes activity as a protective role against the consequences of hyperglycemia and male sub-infertility.

Exploring the therapeutic potential of Adathoda vasica and Andrographis paniculata in alleviating diabetic cardiopathy and neuropathy: A study on high-fat diet and low-dose STZ-induced rat model

Diabetes mellitus is the metabolic illness, if it is left untreated it leads to secondary complications especially in patients suffering from T2DM. Herbal drugs are in medical use since ages. It is found that both Adathoda vasica and Andrographis paniculata exhibited anti-diabetic activity. Therefore, this study is aimed to explore their therapeutic effects in alleviating the secondary complications like neuropathy, cardiopathy using HFD-low dose STZ experimental model. Present study is designed to explore the therapeutic potential of an aqueous ethanolic extract of Adathoda vasica and Andrographis paniculata in alleviating diabetic cardiopathy and neuropathy against HFD-low dose of STZ induced diabetic model. Diabetes was induced by treating the animals with HFD-low dose of STZ injection. Diabetic animals were selected for further investigation on cardiopathy and neuropathy where untreated and treated (Pioglitazone, increasing doses of AEEAV, AEEAP) diabetic animals were subjected to Eddy’s hot plate test, Tail immersion test and Charcoal meal test. Oxidative parameters (MDA, GSH, SOD, CAT) were measured from sciatic nerve and heart homogenate, serum CK-MB, LDH, TC, TG, LDL and HDL were also measured. AEEAP showed improvement in intestinal transit time (P<0.001), restored antioxidants and reduced MDA levels in comparison with untreated diabetic animals (P<0.001). Cardiac biomarkers like CK-MB, LDH, TC, TG, LDL were significantly reduced in dose dependent manner (P<0.001) whereas HDL was found to be increased in treated diabetic animals. In addition, histopathology studies were well co-related with bio chemical improvement. Therefore, aqueous ethanolic extract of Adathoda vasica and Andrographis paniculata alleviates diabetic cardiopathy and neuropathy in HFD- STZ model of diabetes.

Argyreia nervosa Mitigates Insulin Resistance in Liver via IR/IRS-1 Mediated Signaling in Streptozotocin-Induced Type-2 Diabetic Rats

Argyreia nervosa, commonly known as Hawaiian baby woodrose or wooly morning glory, is a plant native to India and is also found in various parts of the world. It is known for its seeds, which have been used traditionally in Ayurvedic and traditional medicine systems for various diseases. The study was aimed at assessing the effect of Argyreia nervosa on insulin signaling molecules of the liver in streptozotocin (STZ)-induced experimental type-2 diabetic rats. Healthy adult male Wistar albino rats -150-180 days old weighing 180-200g was used for the study and divided as Group I - Normal rats; Group II – type-2 diabetic rats; Group III -Diabetic rats + A. nervosa 500 mg/kg b.wt; Group IV-Normal rats + A. nervosa 500 mg/kg b.wt. Fasting blood glucose, and fasting serum insulin were measured by calorimetric methods. Further mRNA expression analysis of insulin receptor (IR) was measured in control and treated animals by quantitative Ream Time PCR analysis. A. nervosa root extract significantly reduced fasting blood glucose and serum insulin concentrations in STZ-induced rats compared with control. In addition, mRNA expression of IR showed a one-fold increase in the expression which shows that A. nervosa is involved in the regulation of insulin signaling in the liver and thereby reduces insulin resistance and type-2 diabetes. Our study concludes that A. nervosa root extract has a significant role on insulin signaling molecules thereby it reduces hyperglycemia and hyperinsulinemia via insulin receptor-mediated pathways. Hence, A. nervosa may be considered as one of the therapeutic natural antidiabetic drugs.

Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models.

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.

Harmine alleviated STZ-induced rat diabetic nephropathy: A potential role via regulating AMPK/Nrf2 pathway and deactivating ataxia-telangiectasia mutated (ATM) signaling

Diabetic nephropathy (DN) is a serious kidney disorder driven by diabetes and affects people all over the world. One of the mechanisms promoting NF-κB-induced renal inflammation and injury has been theorized to be ATM signaling. On the other hand, AMPK, which can be activated by the naturally occurring alkaloid harmine (HAR), has been proposed to stop that action. As a result, the goal of this study was to evaluate the therapeutic effectiveness of HAR against streptozotocin (STZ)-induced DN in rats through AMPK-mediated inactivation of ATM pathways. Twenty male Wistar rats were grouped into 4 groups, as follow: CONT, DN, HAR (10 mg/kg), DN + HAR, where HAR was daily administered I.P. once for 2 weeks. The renal AMPK and PGC-1α expressions, as well as Sirt1 levels, were assessed. To ascertain the oxidative reactions, renal Nrf2 expression, HO-1, MDA, and TAC concentrations were measured. As parts of ATM pathways, ATM and p53 expressions, in addition to GSK-3β levels were determined. Renal expression of NEMO, TNF-α, and IL-6 levels were also estimated. Moreover, histopathological and immunohistochemical detection of Bcl-2, Bax, and caspase 3 were reported. Results indicated that HAR intake notably alleviated STZ-induced kidney damage by triggering AMPK and Sirt1, which in turn boosted PGC-1α, improved NRf2/HO-1 axis, and lowered ROS production. As a consequence, HAR blocked the ATM-triggered renal inflammation and minimized caspase-3 expression by repressing the Bax/Bcl2 ratio. Because of its ability to activate AMPK/Nrf2 axis, HAR may represent an emerging avenue for future DN therapy by blocking ATM pathways.

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1β (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at −7.489, −6.381, −6.742, −7.202, and −8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent. Communicated by Ramaswamy H. Sarma

UJI EFEK EKSTRAK ETANOL UMBI TALAS HISTOPATOLOGI GINJAL TIKUS PUTIH JANTAN (Rattus norvegicus) DIINDUKSI STREPTOZOTOCIN

Diabetes mellitus is a systemic disease or metabolic syndrome caused by chronic disorders, especially in the body's carbohydrate, fat, and protein metabolism system. This study aims to determine the content of secondary metabolites of alkaloids, flavonoids, saponins, and tannins in the ethanolic extract of taro tubers and determine the effect and effective dose of the extract on the regeneration of kidney organ cells in streptozotocin-induced rats. Rats were divided into five groups: normal control, negative control, and extract treatment groups at doses of 100, 200, and 300 mg/kg BW that were performed for 28 days. This study observed changes that occurred in the renal tubular cells of white male rats induced by streptozotocin in the form of the level of damage with a value calculated based on the percentage (%) in each part of the tubule that was injured or damaged. The results showed that the taro tuber extract contained positive secondary metabolites of alkaloids, flavonoids, saponins, and tannins. Administration of ethanol extract of taro tubers at a dose of 300 mg/kg BW can affect the regeneration of kidney tubule cells in STZ-induced rats, with an average damage value of 1 out of a maximum of 4.

Melatonin improves cognitive dysfunction and decreases gliosis in the streptozotocin-induced rat model of sporadic Alzheimer's disease.

Alzheimer's disease (AD) and other forms of dementia have a devastating effect on the community and healthcare system, as neurodegenerative diseases are causing disability and dependency in older population. Pharmacological treatment options are limited to symptomatic alleviation of cholinergic deficit and accelerated clearance of β-amyloid aggregates, but accessible disease-modifying interventions are needed especially in the early phase of AD. Melatonin was previously demonstrated to improve cognitive function in clinical setting and experimental studies also. In this study, the influence of melatonin supplementation was studied on behavioral parameters and morphological aspects of the hippocampus and amygdala of rats. Streptozotocin (STZ) was injected intracerebroventricularly to induce AD-like symptoms in male adult Wistar rats (n = 18) which were compared to age-matched, sham-operated animals (n = 16). Melatonin was administered once daily in a dose of 20mg/kg body weight by oral route. Behavioral analysis included open-field, novel object recognition, and radial-arm maze tests. TNF-α and MMP-9 levels were determined from blood samples to assess the anti-inflammatory and neuroprotective effects of melatonin. Immunohistological staining of brain sections was performed using anti-NeuN, anti-IBA-1, and anti-GFAP primary antibodies to evaluate the cellular reorganization of hippocampus. The results show that after 40days of treatment, melatonin improved the cognitive performance of STZ-induced rats and reduced the activation of microglia in both CA1 and CA3 regions of the hippocampus. STZ-injected animals had higher levels of GFAP-labeled astrocytes in the CA1 region, but melatonin treatment reduced this to that of the control group. In conclusion, melatonin may be a potential therapeutic option for treating AD-like cognitive decline and neuroinflammation.

Ameliorative Effects of Cumin Extract-Encapsulated Chitosan Nanoparticles on Skeletal Muscle Atrophy and Grip Strength in Streptozotocin-Induced Diabetic Rats.

Skeletal muscle atrophy is a disorder characterized by reductions in muscle size and strength. Cumin extract (CE) possesses anti-inflammatory, antioxidant, and hypoglycemic properties. Its pharmaceutical applications are hindered by its low water solubility and by its cytotoxicity when administered at high doses. In this study, we have developed a simplified water distillation method using a rotary evaporator to isolate the active components in cumin seeds. The anti-inflammatory effects of CE and its potential to ameliorate skeletal muscle atrophy in rats with streptozotocin (STZ)-induced diabetes were evaluated. The half-maximal inhibitory concentration (IC50) of CE for cells was 80 μM. By encapsulating CE in chitosan nanoparticles (CECNs), an encapsulation efficacy of 87.1% was achieved with a slow release of 90% of CE after 24 h of culturing, resulting in CECNs with significantly reduced cytotoxicity (IC50, 1.2 mM). Both CE and CECNs significantly reduced the inflammatory response in interleukin (IL)-6 and IL-1β assays. STZ-induced diabetic rats exhibited sustained high blood glucose levels (>16.5 mmol/L), small and damaged pancreatic β islets, and skeletal muscle atrophy. CE and CECN treatments ameliorated skeletal muscle atrophy, recovered muscle fiber striated appearance, increased grip strength, and decreased IL-6 level. Furthermore, CE and CECNs led to a reduction of damage to the pancreas, restoring its morphological phenotype, increasing serum insulin levels, and lowering blood glucose levels in STZ-induced diabetic rats. Taken together, treatment with CECNs over a 6-week period yielded positive ameliorative effects in STZ-induced rats of muscle atrophy.

Scutellarin Alleviates Diabetic Retinopathy via the Suppression of Nucleotide-Binding Oligomerization Domain (NOD)-Like Receptor Pyrin Domain Containing Protein 3 Inflammasome Activation

Purpose Diabetic retinopathy, a prevalent complication of diabetes, represents the leading cause of vision loss and blindness among middle-aged and elderly populations. Recent research has demonstrated the ameliorating effects of scutellarin on diabetes-associated complications such as diabetic retinopathy and type 2 diabetic cardiomyopathy. However, investigations into its protective impact and underlying mechanisms on diabetic retinopathy are scant. This study aims to explore the therapeutic potential of scutellarin in diabetic retinopathy treatment. Methods Diabetic retinopathy was induced in rats through intraperitoneal injections of streptozotocin (STZ, 60 mg/kg) administered daily for three consecutive days. Following this, diabetic retinopathy rats received daily intragastric administration of scutellarin (40 mg/kg) for 42 days. Results Our findings suggest that scutellarin alleviates histological damage in the retinal tissues of streptozotocin-challenged rats. Furthermore, scutellarin effectively enhances total retinal thickness and increases the number of ganglion cell layer (GCL) cells in the retinal tissues of streptozotocin-treated rats. Scutellarin also demonstrated anti-inflammatory and antioxidant effects in the retinal tissues of STZ-induced rats, as indicated by reduced levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, and elevated levels of glutathione peroxidase, superoxide dismutase, and catalase. Additionally, scutellarin effectively inhibited the expression of NOD-like receptor pyrin domain containing protein 3 inflammasome-related markers in the retinal tissues of streptozotocin-administered rats. Conclusions Collectively, our results indicate that scutellarin significantly reduces streptozotocin-induced retinal inflammation, an effect that may be partially attributed to the suppression of NLRP3 inflammasome activation.

Exendin-4, a GLP-1 receptor agonist, suppresses diabetic retinopathy in vivo and in vitro

Diabetic retinopathy (DR) is a complication of diabetes and a leading cause of blindness in adults. Studies have shown that glucagon-like peptide-1 (GLP-1) exerts a protective effect on patients with DR. Here, we investigated the protective effects of Exendin-4, a GLP-1 analogue, on DR. We established a high-glucose-induced HREC cell model and an STZ-induced rat DR Model to study the effect of Exendin-4 in DR in vitro and in vivo. The qRT-PCR, CCK-8, TUNEL, western blotting, tube formation assays, and ELISA were performed. In addition, we overexpressed TGFB2 to observe whether the protective effect of Exendin-4 was reversed. Our results showed that Exendin-4 inhibited the progression of DR. Furthermore, the protective effect of Exendin-4 was suppressed in cells overexpressing TGFB2. Our findings suggest that Exendin-4 may be involved in the regulation of TGFB2 expression levels to inhibit DR. These results indicate that Exendin-4 could be an effective therapy for DR.

Protective Effects of Ginger Extract on Oxidative Stress and Steroidogenesis-related Genes in The Ovary of Streptozotocin-induced Diabetic Rats

Background and Aims: Ginger has anti-oxidant and anti-diabetic properties, but its beneficial effects have not been fully understood on ovarian disorders in diabetic conditions. In the current project, the impact of ginger extract was investigated on oxidative stress and steroidogenesis-related genes in streptozotocin (STZ)-induced female rats. &#x0D; Materials and Methods: The STZ-induced rats were utilized as a diabetic model and received 200 or 400 mg/kg/day ginger extract for eight weeks. The biochemical factors were measured by standard procedures in this study. Serum levels of insulin and sex hormones were assessed by the enzyme-linked immunosorbent assay (ELISA) technique, and the mRNA expression of target genes was assayed by real-time polymerase chain reaction.&#x0D; Results: An increase in the levels of glucose, testosterone, and malondialdehyde (MDA) as well as a decrease in the levels of insulin, glutathione peroxidase (GPx), 3β-hydroxysteroid dehydrogenase (3βHSD), steroidogenic acute regulatory protein (StAR), 17β-estradiol, and progesterone was observed in the diabetic rats. Ginger (200 mg/kg) exhibited a significant amelioration in the levels of glucose, testosterone, and MDA. Treatment with 200 mg/kg ginger enhanced the levels of GPx, StAR, and 17β-estradiol. Administration with 400 mg/kg ginger extract also ameliorated the level of glucose, testosterone, MDA, and elevated the level of insulin, GPx, 3βHSD, StAR, 17β-estradiol, and progesterone in the diabetic rats.&#x0D; Conclusion: The current study suggests ginger extract protects against ovarian damage in STZ-diabetic rats.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1β. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Effects of thymoquinone and memantine alone and in combination on memory and hippocampal morphology in rats with streptozotocin-induced Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Thymoquinone (TQ) has broad biological functions, including antiinflammatory, antioxidant, neuroprotective properties. Memantine (MEM) is indicated for the symptomatic treatment of moderate to severe AD. We aimed to evaluate the effect of TQ alone or in combination with MEM on memory and hippocampal morphology in an STZ-induced rat AD model. Thirty male rats were included in this study. The AD model was created by giving ICV STZ. The rats were divided into 5 groups (n = 6 each). Group 1 (control group): The rats received only ICV-STZ 3 mg/kg for 2 weeks. Group 2 (sham group): In addition to ICV STZ, 9% NaCl, 1 mL/day i.p. for 2 weeks of injection, was applied. Group 3 (TQ group): In addition to ICV STZ, rats received TQ 10 mg/kg i.p. for 2 weeks. Group 4 (MEM group): In addition to ICV STZ, rats were given MEM at a dose of 5 mg/kg for two weeks. Group 5 (TQ+MEM group): In addition to ICV STZ, this group was given TQ (10 mg/kg/day, i.p.) and MEM (5 mg/kg/day, i.p.) for 2 weeks. On the 15th day, passive avoidance learning (PAL) was applied to all groups. Then, rats were sacrificed, neurons in the hippocampal CA1, CA2, CA3 regions were evaluated. Groups 3, 4, 5 had longer latency periods than groups 1 and 2. The neuron density in the CA1, CA2, CA3 regions had decreased in groups 1 and 2 compared to groups 3, 4, 5. There were significantly more neurons in groups 3, 4, 5 than in groups 1 and 2. We found that TQ alone and in combination with MEM showed ameliorative effects on memory and hippocampal morphology. TQ may offer a promising treatment strategy for AD.

Total flavonoids of Hippophae rhamnoides L. improves type 2 diabetes symptoms in rats through down-regulating of the DAG/PRKCA/MAPK10/p65/TNF-α signalling pathway

Ethnopharmacological relevanceDry mature fruits of Hippophae rhamnoides L. (HRL), Elaeagnaceae, have traditional functions of invigorating spleen and improving spleen insufficiency. Traditional Chinese medicine (TCM) clinics have been proved that HRL is in favor of diabetes treatment. Modern pharmacological studies demonstrated that total flavones of Hippophae rhamnoides (TFH) are the main substance for HRL to develop anti-inflammation and anti-diabetes functions. However, chemical features, active ingredients and anti-diabetes pharmacological mechanism of HRL still remain unclear. Aim of the studyKey targets and metabolites in anti-type-II diabetes mellitus (T2DM) of TFH have been explored based on AGE-RAGE signaling pathway in diabetic complications. The anti-T2DM mechanism of TFH has been elaborated from comprehensive perspectives, including target prediction, metabolites, potential metabolic pathways, and so on. Materials and methodsIn this study, a qualitative test of chemical composition of HRL was carried out based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The anti-T2DM targets and pathways of HRL were predicted through network pharmacological approach. The T2DM rat model was induced by high-fat and high-glucose diet combined with streptozotocin (STZ). The T2DM model was evaluated through fasting blood glucose level, body weight, serum biochemical indicators, insulin levels and homeostatic model assessment of insulin resistance. The key metabolic pathways were screened through the correlation between metabolites and key targets. Finally, the quantitative analysis of key targets and metabolites was verified through experiments. ResultsAfter TFH intervention, the fasting blood-glucose level of T2DM rats induced by high-fat and high-glucose diet combined with streptozotocin (STZ) was downregulated significantly, while body weight, serum liquid level, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) were improved. According to ELISA, Western blotting (WB) and reverse transcriptase polymerase chain reaction (RT-PCR), TFH significantly downregulates expression levels of diglyceride (DAG)-activated protein kinase C (PRKCA), mitogen activated protein kinase 10 (MAPK10), human nuclear factor κB subunit p65 (NF-κB p65) and tumor necrosis factor-α (TNF-α) in pancreas of STZ-induced rats. ConclusionsTFH downregulates expressions of PRKCA, MAPK10 and p65 TNF-α as well as level of the key metabolite DA in the DAG/PRKCA/MAPK10/TNF-α/p65 pathways, improves lipid metabolism disorder, inhibits inflammatory response and thereby relieves symptoms of T2DM.

Phytochemical Screening And Antidiabetic Test Of Ethanol Extract Of Turmeric Leaves (Curcuma domestica Val.) On Decreasing Blood Glucose Of Diabetic Rats

The turmeric plant (Curcuma domestica Val.) is a tropical plant that grows a lot on the Asian continent with is use as a food coloring and fragrance. The use of turmeric leaves by residents is only a cooking ingredient not used in large quantities. Even most of these turmeric leaves are considered waste and have minimal utilization. Turmeric leaf methanol extract can be used to lower blood glucose. Turmeric leaf extract has the potential as a valuable food source of its antioxidant components, such as total phenolic compounds and flavonoids which increase radical scavenging activity. In particular, the water extract of turmeric leaves contains high total phenolic compounds (2.741 ± 0.099 mg GAE/g) and flavonoids (4.776 ± 0.010 mg QCE/g). Diabetes mellitus is a metabolic disorder associated with several chronic complications, such as nephropathy, neuropathy, retinopathy and cardiomyopathy. Part of the turmeric plant leaves is reported to have the ability as an antioxidant. Antioxidant compounds can control blood glucose levels and prevent diabetes complications. This study was conducted to test the ability of turmeric leaf ethanol extract (EEDK) to reduce blood glucose levels in diabetic rats induced by nicotinamide and streptozotocin and to perform phytochemical screening to determine the compounds contained in turmeric leaves so that it becomes an alternative as a diabetes treatment and can prevent damage. or diabetic complications. The results showed that turmeric leaves contained secondary metabolites, namely flavonoids, glycosides, tannins, and triterpenoids/steroids, but there were no alkaloids or saponins. The characterization results show that the sample meets the requirements. Turmeric leaf ethanol extract doses of 400 mg/kg, 200 mg/kg, and 100 mg/kg could reduce the Blood Glucose Level of NA and STZ-induced rats from the fourth day of treatment.

Hepatoprotective effects of N-acetylcysteine on liver injury by irisin upregulation and oxidative stress reduction in diabetic rats

BackgroundThe current study aimed to investigate the oxidative stress in rat liver with diabetes mellitus (DM) as well as the protective effects of N-acetylcysteine (NAC) on irisin expression.MethodsTwenty-eight male Wistar rats were divided into four groups, 7 rats in each group, and 30-day regimens of experimental or control groups. NAC-treated group is as follows: 100 mg/kg once daily was administered intraperitoneally (i.p.). Diabetes-induced group is as follows: single-dose intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) was used to induce DM in overnight fasting Wistar rats. By determining blood glucose concentration in STZ-induced rats 72 h after injection of STZ, DM was assessed. DM + NAC group is as follows: STZ-induced DM plus NAC is described previously. On the 30th day of the experiment, liver samples were collected after fasting and anesthesia. Biochemical analyses were performed to measure total antioxidant status (TAS), total oxidant status (TOS), and malondialdehyde (MDA) levels. Each liver sample was weighed and then prepared for histopathologic evaluation by light microscopy.ResultsThere was a statistically significant decrease in TAS levels and an increase in TOS and MDA levels in the DM group compared to the control group. In contrast, TOS and MDA levels were found significantly decreased, and TAS levels increased in the serum and liver tissues of the DM + NAC group compared to the DM group. Liver samples were also used for histopathological examination using hematoxylin-eosin and immunohistochemical staining. STZ-induced liver damage was detected as oxidative stress, increased irisin immunoreactivity, sinusoidal dilatation, and hepatocyte degeneration. In the DM + NAC group, it was observed that NAC significantly reduced the aforementioned histopathological changes due to STZ.ConclusionIn the early period of diabetes, due to the antioxidant properties of irisin related to the sudden response of liver tissue to oxidative stress, it is thought that the immunoreactivity in the tissue increases in the early period. As a result, NAC in diabetic rat liver tissue was found to suppress oxidative damage and irisin immunoreactivity.

The Renoprotective Effect of Shikonin in a Rat Model of Diabetic Kidney Disease

In diabetes mellitus, diabetic nephropathy (DN) is a typical complication and pivotal cause of chronic kidney disease. The DN disease burden is among the highest in the world and is associated with high morbidity, mortality, and disease burden. Safe and effective medications are urgently needed for the treatment of DN. Interest has been increasing in Shikonin, extracted from the naphthoquinone plant, particularly in determining its renal protective effect. In this study, we explored Shikonin's effects and potential mechanisms on a streptozotocin (STZ)-induced DN experimental model. An STZ-induced rat diabetic model was established, and the rats were treated with different doses of Shikonin (10/50 mg/kg) for 4 weeks. Blood, urine, and renal tissue samples were collected after the last administration. Renal tissues were examined to detect each group's physiologic, biochemical, histopathologic, and molecular changes. The results showed that Shikonin administration could significantly alleviate the STZ-induced elevation of blood urea nitrogen, serum creatinine, urinary protein content, and renal pathologic injury. Furthermore, Shikonin significantly decreased oxidative stress, inflammation, and Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-κB expression levels in DN kidney tissues. Shikonin showed a dose-dependent effect, with the best outcome at 50 mg/kg. Shikonin could effectively alleviate DN-related nephropathy damage and reveal the underlying pharmacologic mechanism. Based on the results, a Shikonin combination can be used in clinical treatment.