Complications In Diabetic Rats Research Articles

Impacts of Plu kaow (Houttuynia cordata Thunb.) Ethanolic Extract on Diabetes and Dyslipidemia in STZ Induced Diabetic Rats: Phytochemical Profiling, Cheminformatics Analyses, and Molecular Docking Studies.

The increasing prevalence of diabetes and dyslipidemia poses significant health challenges, impacting millions of people globally and leading to high rates of illness and death. This study aimed to explore the potential antidiabetic and hypolipidemic effects of Plu kaow (Houttuynia cordata Thunb.) ethanolic extract (PK) in streptozotocin (STZ) induced diabetic rats, focusing on its molecular mechanisms. Diabetes was induced in fasting Long Evans rats using streptozotocin (65 mg/kg b. w.), with glibenclamide (5 mg/kg/day) used as the standard experimental drug. The treated groups received oral supplementation of PK (500 mg/kg/day) for 28 days. The study evaluated blood glucose levels, lipid status, body weight, liver, kidney, and heart function biomarkers, antioxidant activity, and histological examination of various organs. Additionally, untargeted metabolomics, cheminformatics, and molecular docking were employed to elucidate the probable mechanisms of action of PK. Based on metabolomic profiling data, the PK was found to contain various putative antidiabetic agents such as kaempferol 7-neohesperidoside, isochlorogenic acid C, rutin, datiscin, and diosmin and they have been proposed to significantly (p < 0.001) reduce blood glucose levels and modulated hyperlipidemia. PK also improved the tested liver, kidney, and heart function biomarkers and reversed damage to normal pancreatic, liver, kidney, and heart cells in histological analysis. In conclusion, PK shows promise as a potential treatment or management option for diabetes and hyperlipidemia, as well as their associated complications in diabetic rats.

Pharmacological mechanisms of Taohe Chengqi decoction in diabetic cardiovascular complications: A systematic review, network pharmacology and molecular docking

BackgroundDiabetic cardiovascular complications are the leading cause of diabetes-related deaths. These complications place an enormous and growing burden on global health systems and economies. The objective of this study was to conduct a systematic review on the therapeutic mechanisms of Taohe Chengqi Decoction (THCQD) in the treatment of diabetic cardiovascular complications. To predict the potential mechanisms of action of THCQD on diabetic cardiovascular complications using network pharmacology, and to validate these predictions through molecular docking analysis. MethodsTo collect relevant animal experiments, we searched a total of 6 databases. Eligibility for the study was determined based on inclusion and exclusion criteria. Data extraction was then performed on the literature. Methodological quality of animal studies was assessed using SYRCLE criteria. Based on network pharmacology, intersecting genes for THCQD and diabetic cardiovascular complications were obtained using Venny, PPI analysis and topology analysis of intersecting genes were performed; GO and KEGG were used for enrichment analysis and prediction of new targets of action. Molecular docking techniques were employed to model the interactions between drug components and target genes, thereby validating the results of network pharmacology predictions. ResultsA total of 16 studies were finally identified that fit the direction of this review. Included 6 studies of the myocardium, 1 study of the aortic arch, 5 studies of the femoral artery, 4 studies of the thoracic aorta. THCQD exhibited anti-inflammatory, anti-fibrotic and anti-atherosclerotic effects on cardiovascular complications in diabetic rats. Network pharmacology results showed that C0363 (Resveratrol), C0041 (Emodin), and C1114 (Baicalein) were the key components in the treatment of diabetic cardiovascular complications by THCQD. PPI results showed that INS, AKT1, TNF, ALB, IL6, IL1B as the genes that interact with the top 6. KEGG enrichment analysis identified the AGE-RAGE signaling pathway in diabetic complications as the most prominent pathway enriched by THCQD for diabetic cardiovascular complications genes. The results of molecular docking showed that the key active components demonstrated favorable interactions with their corresponding target genes. ConclusionIn conclusion, the results of both basic and web-based pharmacological studies support the beneficial effects of the natural herbal formulation THCQD on diabetic cardiovascular complications. This decoction has anti-inflammatory and antifibrotic properties and is effective in ameliorating diabetic cardiovascular disease. The network pharmacology results further support these ideas and identify the AGE-RAGE signaling pathway in diabetic complications as possibly the most relevant pathway for THCQD in the treatment of diabetic cardiovascular complications. The extent of the therapeutic potential of all-natural herbal components in the treatment of diabetic cardiovascular disease merits further investigation.

Co-administration of “L-Lysine, Vitamin C, and Zinc” increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats

PurposeWe previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. MethodsThe streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. ResultsThe determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. ConclusionsThe results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.

Rod Uncaria Gambir (W. Hunter) Roxb.'S Antioxidant Activity In Streptozotocin-Induced Diabetic Rats

To ascertain whether Uncaria gambir (W. Hunter) Roxb.'s ethanol extract can reduce diabetes complications due to its antioxidant activity. Sprague Dawley rats with diabetes were induced by streptozotocin. Twenty-five rats were divided into four groups: the negative control (k-), which received 1% Na-CMC; the extract group (P1, P2, and P3) with doses of 50 mg/Kg BW, 75 mg/Kg BW, and 100 mg/Kg BW for 21 days. Rats received therapy for 21 days before being fasted the following morning and sacrificed. Measure the level of Hydrogen peroxide, Malondialdehyde (MDA), changes in Catalase activity, and Superoxide Dismutase (SOD) levels in blood plasma used spectrophotometric. In comparison to diabetic rats receiving of Na-CMC, and ethanol extract for 21 days resulted in noticeably greater Catalase enzyme activity and a decrease in levels of Malonaldehyde and Hydrogen Peroxidas However, it was unable to boost superoxide dismutase activity. Uncaria gambir (W.Hunter) Roxb. extract has the ability to prevent diabetic complications in diabetic rats due to its antioxidant activity and previously noted antihyperglycemic effects

The Protective Effects of Aloe Vera Gel Extract on the Sexual Complications Caused by Diabetes in Male Rats

Introduction: Diabetics usually suffer from chronic complications, including microvascular and macrovascular disorders. The capillaries supplying the sexual organs affect normal sexual functions. The erectile process has been shown to be impaired in diabetics. Vascular damage in diabetics may be associated with decreased testosterone production, sperm count, testicular weight, and seminiferous tubule diameter. In this study, we investigated the effects of Aloe vera gel extract (from Sistan and Baluchistan, Iran) on the male genital system in streptozocin-induced diabetic rats. Methods: A total of 24 male Wistar rats were included in the study. Diabetes was induced in 12 rats by intraperitoneal injection of a single dose of streptozotocin (STZ). The rats were divided into four groups. The first and third groups received saline (NaCl) by gavage daily. The second and fourth groups received Aloe vera gel extract daily by gavage. Treatments were continued for 30 days. At the end of the treatment period, blood samples were taken and serum glucose and testosterone levels were measured by photometric methods. Histological examinations were performed on the prostate and testes. Results: Mean weight index, serum levels of glucose and testosterone, mean sperm count, germinal epithelium (GE) thickness, and seminiferous tubule diameter improved significantly in the diabetes+Aloe vera group. Conclusion: We concluded that consumption of Aloe vera gel extract improved sexual complications in diabetic rats.

Effect of zinc oxide nanoparticles on diabetes development and complications in diabetic rats compared to conventional zinc sulfate and metformin

Diabetes mellitus (DM) is a metabolic disorder with numerous secondary complications. Herein, the effect of zinc oxide-nanoparticles (ZnO-NPs), zinc sulfate-traditional form (ZnSO4-TF) and metformin on the progression of diabetes and its secondary complications in streptozotocin (STZ)-induced diabetic rats were evaluated. To achieve that, fifty male Wistar rats divided into five groups (10/each). The control group (GI) was untreated with STZ. The other groups received a single intraperitoneal dose of STZ (60 mg/kg/body weight (b.wt)) to induce diabetes. They were divided as follows: diabetic rats that did not receive treatment were (GII), while GIII, IV, and V were diabetic rats that received a daily single oral dose via gavage for four weeks of metformin (100 mg/kg b.wt), ZnSO4-TF (10 mg of Zn/kg b.wt), and ZnO-NPs (5 mg of Zn/kg b.wt), respectively. The fasting blood glucose (FBG), insulin resistance, lipid profile, tumor necrosis factor- α (TNF-α) levels, and liver, kidney, and heart functions were investigated. Histopathological examination of the liver, pancreas, and kidneys was performed. The results revealed a reduction in final-FBG levels in GIII, GIV, and GV by 35.1%, 26.8%, and 29.8%, respectively, while insulin levels increased by 38.3%, 32.1%, and 31.3%, respectively, compared with GII. Also, the liver, kidney, and heart functions, as well as most lipid profiles in the ZnO-NPs and ZnSO4-TF groups was improved compared with GII and were further validated by histopathological analysis. In conclusion, the results illustrated that ZnO-NPs exert the same effect of ZnSO4-TF in improving diabetes but at half dose and without inducing toxicity.

Effects of Hypericum scabrum L. essential oil on wound healing in streptozotocin-induced diabetic rats

Background The purpose of this study was to see if the essential oil of Hypericum scabrum L. (H. scabrum L.) has a protective and therapeutic effect on the wound in streptozotocin-induced diabetic rats. Methods In the study, 63 Sprague-Dawley male rats weighing 250–300 g were divided into nine groups, each with seven rats (major groups: control group, diabetes group, and treatment group). For diabetes and treatment groups, streptozotocin (STZ) was given in a single dose of 60 mg/kg/i.p. In 7 days, the animals with diabetes (blood glucose level > 250 mg/dL) will be assigned to wound groups. All of the rats had circular full-thickness incisions in their dorsal skin caused by a 5 mm punch biopsy tool. The rats were slaughtered, blood was obtained, and their forwound tissues were dissected on the 3rd, 10th, and 14th post-wounding days. The levels of malondialdehyde (MDA) and glutathione (GSH), as well as the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in plasma and wound tissues, were all measured. Results While GSH level, GPx, SOD, and CAT activities were decreased in the plasma and wound tissues, MDA level increased in the diabetic group as compared to the control group. When compared to the diabetes group, GSH level, GPx, SOD, and CAT activities were increased in the H. scabrum L. essential oil treatments, but MDA levels were decreased. In comparison to the other groups, the wounds in the H. scabrum L. essential oil diabetic groups healed better and faster. H. scabrum L. essential oil can help to reduce lipid peroxidation, oxidative stress, and the associated complications that come with it, as well as play a beneficial role in the treatment of diabetic wounds. Conclusion Since no information was found in the literature search, future work would focus on new research examining H. scabrum L. essential oil applications to come up with new findings in determining the mechanisms of action of H. scabrum L. essential oil in diabetic wounds and preventing wound healing complications in diabetic rats.

Effects of Ribes khorasanicum hydro-ethanolic extract on streptozotocin-induced diabetic complications in rats.

The anti-diabetic effects of Ribes khorasanicum as a traditional remedy were investigated in diabetic rats. Thirty-five male rats were divided into five groups: control, diabetic, diabetic treated with metformin (300 mg kg-1; D+Met), diabetic treated with 250 and 500 mg kg-1 of Ribes khorasanicum hydro-ethanolic extract (D+Rib250 and D+Rib500). After six weeks of treatment, sera of overnight fasted animals were collected and used for measurement of glucose, insulin, lipid profile, urea, creatinine, and hepatic enzymes levels. Moreover, liver and kidney of rats were removed and used for measurement of oxidative stress including malondialdehyde (MDA), thiol content, and the activity of catalase (CAT) and superoxide dismutase (SOD). Streptozotocin (STZ)-induced diabetes increased the levels of serum glucose, triglycerides (TG), total cholesterol (TC), and LDL-C, urea, creatinine, hepatic enzymes, and kidney and liver oxidative stress markers, while decreased insulin and HDL-C when compared to control group. In all treated groups serum levels of glucose, TC, LDL-C, TG, and urea were decreased, while liver SOD activity was increased compared to the diabetic group. The D+Rib500 group had lower Serum glutamic pyruvic transaminase (SGPT), creatinine, and kidney MDA levels, but higher insulin, HDL-C levels, liver CAT activity, and kidney thiol content, and CAT activity compared to diabetic group. In D+Met group, serum levels of serum glutamic-oxaloacetic transaminase (SGOT), creatinine, and MDA of liver and kidney were decreased, while liver SOD activity was increased compared to the diabetic group. Based on our findings, treatment with Ribes khorasanicum improved diabetic complications, while the effect of a higher dose of the extract was comparable to metformin’s.

Prevention of tubulin/aldose reductase association delays the development of pathological complications in diabetic rats.

In recent studies, we found that compounds derived from phenolic acids (CAFs) prevent the formation of the tubulin/aldose reductase complex and, consequently, may decrease the occurrence or delay the development of secondary pathologies associated with aldose reductase activation in diabetes mellitus. To verify this hypothesis, we determined the effect of CAFs on Na+,K+-ATPase tubulin-dependent activity in COS cells, ex vivo cataract formation in rat lenses and finally, to evaluate the antidiabetic effect of CAFs, diabetes mellitus was induced in Wistar rats, they were treated with different CAFs and four parameters were determinates: cataract formation, erythrocyte deformability, nephropathy and blood pressure. After confirming that CAFs are able to prevent the association between aldose reductase and tubulin, we found that treatment of diabetic rats with these compounds decreased membrane-associated acetylated tubulin, increased NKA activity, and thus reversed the development of four AR-activated complications of diabetes mellitus determined in this work. Based on these results, the existence of a new physiological mechanism is proposed, in which tubulin is a key regulator of aldose reductase activity. This mechanism can explain the incorrect functioning of aldose reductase and Na+,K+-ATPase, two key enzymes in the pathogenesis of diabetes mellitus. Moreover, we found that such alterations can be prevented by CAFs, which are able to dissociate tubulin/aldose reductase complex.

Propolis ethanol extract abrogates hyperglycemia, lipotoxicity, and lowered hepatic poly (ADP-ribose) polymerase protein level in male albino rats.

Diabetes is a major cause of death worldwide and currently available allopathic drugs presents adverse side effects, thus, necessitating a continuous screening for natural products. This study therefore investigated the effects of Propolis Ethanol Extract (PEE) on blood sugar, lipid metabolism, and poly-(ADP)-ribose polymerase (PARPs) protein level of diabetic male Wistar rats. Seventy rats weighing between (150-180) g used in this study were randomized into seven (7) groups as follows: group 1 (Normal control given Olive oil), group 2 (Diabetic control given Olive oil), group 3 [Diabetic + PEE (200mg/kg)], group 4 [Diabetic + (PEE 600mg/kg)], group 5 [Diabetic + Glibenclamide (10mg/kg)], group 6 [Normal + PEE (200mg/kg)], and group 7 [Normal + PEE (600mg/kg)]. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65mg/kg in 0.1M citrate buffer pH 4.5), while the vehicle and PEE were orally administered once daily. Treatment with PEE commenced after the confirmation of diabetes. Five rats from each group were sacrificed after the third and sixth weeks of PEE treatment. Administration of PEE significantly (P < 0.05) lowered the elevated fasting blood sugar, improves body weight, and abated lipotoxicity in the brain, heart, liver and kidney of the treated groups in a dose- and duration-dependent manners. The increased protein level of PARPs and lowered hydroxyl methyl-glutaryl CoA reductase activity were significantly reversed after PEE treatment. This study concludes that PEE might be a suitable and viable regimen against diabetic complications in rats.

Protective effect of flavonoids from Passiflora edulis Sims on diabetic complications in rats.

This study was carried out to evaluate the effects of flavonoids present in leaves of Passiflora edulis fruit on complications induced by diabetes in rats. The extract of P. edulis leaf was obtained by 70% ethanol maceration. From the dry extract, the fractions were obtained by consecutive liquid-liquid partition with hexane, ethyl acetate and n-butanol. The content of isoorientin of ethyl acetate and n-butanol fractions was determined by ultra-performance liquid chromatography coupled with electrospray and triple quadrupole ionization (TQD) analysis in tandem mass spectrometry (UPLC-ESI-Tq-MS). Only Fr-BuOH was used to treat diabetic or not Wistar rats. Biochemical parameters, platelet aggregation and production of reactive species were evaluated. The UPLC-ESI-Tq-MS analysis revealed the presence of several flavonoids, among which we identified five possible flavonoids c-heterosides (luteolin-7-O-pyranosyl-3-O-glucoside, apigenin-6-8-di-C-glycoside, apigenin-6-C-arabinoside-8-C-glycoside, isoorientin, isovitexin). The diabetic rats (treated intraperitoneally with alloxan, 150 mg/kg) treated with Fr-BuOH (20 mg/kg/day for 90 days) presented improvement in blood glucose, serum levels of fructosamine, lipid profile and urea. Furthermore, the Fr-BuOH reduced both platelet aggregation and the production of oxidant species in diabetic animals. These results suggested that flavonoid C-glycosides present in the Fr-BuOH may be beneficial for the diabetic state, preventing complications induced by diabetes.

Role of Artesunate on cardiovascular complications in rats with type 1 diabetes mellitus

BackgroundThe present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway.MethodsA total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR.ResultsThe results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05).ConclusionsART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.

Efficiency of a formulated condiment (duqqa) in mitigation of diabetes and its complications induced by streptozotocin-nicotinamide in rats

Introduction: Duqqa is a condiment, consisting of black pepper, cumin, sesame, coriander and high amount of salt. Reducing salt and adding other beneficial items to traditional duqqa can make it suitable dietary supplement for diabetes management. The current study aimed to assess the effect of a modified duqqa on diabetes and its complications in diabetic rats. Methods: The modified duqqa was formulated by mixing grounded fermented wheat, sesame, coriander, cumin, chicory leaves, cinnamon, turmeric and date seeds powder and studied in diabetic rats which were developed by streptozotocin-nicotinamide injection. Thirty-two rats were divided into four groups (n = 8) including non-diabetic, diabetic control and the other two groups fed on balanced diet supplemented with either 10 or 20% of duqqa prior the induction of diabetes (for one week) to the end of the experiment (8 weeks). Results: The dietary supplementation with 10 and 20% of the formulated duqqa prior the induction of diabetes did not delay the onset of diabetes in rats but produced reduction (32.56% and 50.47%, respectively) in the glucose levels of diabetic rats. Also, diabetic rats fed on the formulated duqqa showed insulin concentrations higher than that of diabetic control rats. Feeding diabetic rats on the formulated duqqa reversed the elevation of kidney lipid peroxidation and nitric oxide, limited the disturbance in the lipid profile as well as liver and kidney functions and elevated both serum and femur magnesium concentrations. Conclusion: The results indicated the hypoglycemic effect of the formulated duqqa and its efficiency in delaying diabetes complications.

Protective effects of the novel amine-oxidase inhibitor multi-target drug SZV 1287 on streptozotocin-induced beta cell damage and diabetic complications in rats

Diabetes mellitus is a common metabolic disease leading to hyperglycemia due to insufficient pancreatic insulin production or effect. Amine oxidase copper containing 3 (AOC3) is an enzyme that belongs to the semicarbazide-sensitive amine oxidase family, which may be a novel therapeutic target to treat diabetic complications. We aimed to explore the effects of AOC3 inhibition and to test the actions of our novel AOC3 inhibitor multi-target drug candidate, SZV 1287, compared to a selective reference compound, LJP 1207, in an 8-week long insulin-controlled streptozotocin (STZ)-induced (60 mg/kg i.p.) rat diabetes model. Both AOC3 inhibitors (20 mg/kg, daily s.c. injections) were protective against STZ-induced pancreatic beta cell damage determined by insulin immunohistochemistry and radioimmunoassay, neuropathic cold hypersensitivity measured by paw withdrawal latency decrease from 0 °C water, and retinal dysfunction detected by electroretinography. SZV 1287 showed greater inhibitory effects on beta cell damage, and reduced retinal apoptosis shown by histochemistry. Mechanical hypersensitivity measured by aesthesiometry, cardiac dysfunction and nitrosative stress determined by echocardiography and immunohistochemistry/Western blot, respectively, serum Na+, K+, fructosamine, and urine microalbumin, creatinine, total protein/creatinine ratio alterations did not develop in response to diabetes. None of these parameters were influenced by the treatments except for SZV 1287 reducing serum fructosamine and LJP 1207 increasing urine creatinine. We provide the first evidence for protective effects of AOC3 inhibition on STZ-induced pancreatic beta cell damage, neuropathic cold hypersensitivity and diabetic retinal dysfunction. Long-term treatment with our novel multi-target analgesic candidate, SZV 1287, is safe and effective also under diabetic conditions.

Antioxidant activities of Dhanwantaram Kashayam -an Ayurvedic poly herbal formulation alleviates diabetic complications in rats.

Phytochemicals of ethno medicines are being developed as effective drugs with minimum or no toxic side effects. Dhanwantaram Kashayam (DK) is a polyherbal formulation used as a potent general health tonic and is found to have antioxidant activities, but there are no proper scientific studies on its possible benefits. In this study we investigated the antioxidant and antidiabetic properties of DK and trying to explore the possibility of employing DK for the treatment of diseases like diabetes mellitus caused by the imbalance in Reactive Oxygen Species (ROS). We investigated the effect of DK on normal and rat model of diabetes. Rats were fed with DK for 21days. Fasting blood glucose level, haemoglobin, glycosylated hemoglobin, non enzymatic antioxidants like vitamin C, vitamin E, reduced glutathione, and MDA were evaluated. DK was found to ameliorate the disease symptoms of diabetes. A significant decrease in non enzymatic antioxidants - vitamin C, vitamin E, reduced glutathione and an increase in MDA and fasting blood glucose level was observed in diabetic rats. Administration of DK resulted significant increase in non enzymatic antioxidant levels both in diabetic and normal rats and a decrease in MDA, fasting blood glucose, glycosylated hemoglobin and HOMA-IR index was observed. This study reveals the protective role of DK in diabetic condition through its antioxidant and antihyperglycemic activity. Our results strongly indicate the possibility of DK being developed as a potent antidiabetic drug. DK could be an alternative in the treatment of diseases with ROS imbalance to expensive and toxic synthetic 'medicines'.

Therapeutic Effects of 5,7-Dihydroxy-6-Oxoheptadecanoic Acid on Dysglycemia, Dyslipidemia, and Other Complications in Diabetic Rats

The current study aimed to investigate the therapeutic effects of 5,7-dihydroxy-6-oxoheptadecanoic acid (DHA) from Tiliacora triandra on rat models of type 2 diabetes mellitus (T2DM). T2DM was induced with a combination of high-fat diet/streptozotocin (HFD/STZ), and diabetic rats were treated with DHA (25 mg/kg) for 30 days. The body weight, fasting blood glucose (FBG), serum, and liver biochemical parameters, as well as histological evaluations of the liver and pancreas, were evaluated. Diabetic rats displayed a significant increase in FBG, serum lipid profiles (triglycerides, total cholesterol, and low-density lipoprotein cholesterol), liver function enzymes (aspartate transaminase, alkaline phosphatase, and alanine transaminase), creatinine, liver malondialdehyde (MDA), and myeloperoxidase (MPO) contents. Furthermore, insulin level and liver antioxidant enzyme activities (catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GSH-Px]) were significantly reduced in the diabetic rats. Whereas, treatment with DHA significantly reduced FBG, serum lipids, liver function enzymes, serum creatinine, liver MDA, and MPO contents. In addition, treatment with DHA significantly increased serum insulin level and liver SOD, CAT, and GSH-Px activities. In addition, DHA alleviated histopathological changes in the pancreas and liver caused by T2DM. These results portray the antidiabetic and antioxidative properties of DHA and can be considered as a potential treatment for T2DM.

Suppression of HDAC by sodium acetate rectifies cardiac metabolic disturbance in streptozotocin-nicotinamide-induced diabetic rats.

Diabetes mellitus, particularly type 2 occurs at global epidemic proportions and leads to cardiovascular diseases. Molecular studies suggest the involvement of epigenetic alterations such as histone code modification in the progression of cardiometabolic disorders. However, short chain fatty acids (SCFAs) are recognized as epigenetic modulators by their histone deacetylase inhibitory property. It is therefore hypothesized that cardiac histone deacetylase activity increases in type II diabetes and SCFA, acetate, would inhibit histone deacetylase with accompanying restoration of glucose dysregulation, cardiac lipid deposition, and tissue damage in male Wistar rats. Twenty-four male rats (240–270 g) were allotted into four groups ( n = 6 per group) namely: vehicle-treated ( p.o.), sodium acetate-treated (200 mg/kg), diabetic, and diabetic+sodium acetate-treated groups. Diabetes was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide 110 mg/kg. The results showed that diabetic rats had, glucose dysregulation, elevated serum and cardiac triglyceride, malondialdehyde, alanine aminotransferase, histone deacetylase, serum aspartate transaminase, cardiac low density lipoprotein cholesterol (LDLc), glutathione/glutathione disulphide ratio (GSH/GSSG), reduced serum and cardiac high density lipoprotein cholesterol (HDLc), and serum GSH/GSSG. Histological analysis revealed disrupted cardiac fiber in diabetic rats. However, sodium acetate attenuated glucose dysregulation and improved serum and cardiac GSH/GSSG. Sodium acetate normalized cardiac triglyceride accumulation, malondialdehyde, serum aspartate transaminase levels and prevented cardiac tissue damage in diabetic rats. These effects were associated with suppressed histone deacetylase activity. Therefore, sodium acetate attenuated but failed to normalize glucoregulation. Nevertheless, it ameliorated oxidative stress- and lipid dysmetabolism-driven cardiovascular complications in diabetic rats by the suppression of histone deacetylase activity. Impact statement This study provides evidence that STZ-NA-induced diabetes mellitus is associated with cardiac triglyceride accumulation and tissue disruption with corresponding increase in cardiac HDAC activity. However, sodium acetate suppresses cardiac HDAC activity and normalizes cardiac triglyceride and tissue integrity in diabetic rats. Therefore, the study suggests that sodium acetate is beneficial for cardioprotection in diabetes mellitus.

Anti-hyperglycemic and ameliorative effect of concentrated hot water-infusion of Phragmanthera incana leaves on type 2 diabetes and indices of complications in diabetic rats.

This study investigated the anti-hyperglycemic effects of concentrated hot water infusion of Phragmanthra incana leaves as well as its ameliorative effect on indices related to diabetic complications in a type 2 diabetes model of rats. Type 2 diabetes was induced by feeding 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of streptozotocin (40mg/kg body weight (b.w.)). Concentrated plant infusion was administered orally at a dose of 150 and 300mg/kg b.w. to two type 2 diabetes rat groups. Diabetic rats without treatment served as a negative control while the group administered with metformin was served as a positive control. The intervention lasted for 4weeks when a single oral dose was given daily for 5days a week. Body weight and blood glucose were determined every week. An oral glucose tolerance test was performed in the last week of treatment. The rats were sacrificed after 4weeks of intervention, and the blood and organs were harvested for further analysis. Both dosages of the plant infusion significantly improved body weight, pancreatic β-cell function (HOMA-β), insulin secretion and reduced blood glucose, insulin resistance (HOMA-IR) with concomitant reduction in the elevated level of serum α-amylase activity, fructosamine, uric acid, urea, and liver function enzymes. The liver glycogen content was significantly improved while the activity of liver glucose-6-phosphatase was significantly reduced. The results demonstrate the anti-hyperglycemic ability of P. incana and its ability to delay the onset of diabetic complications which can be exploited for the anti-diabetic drug discovery.

Purine metabolites can indicate diabetes progression

Serum uric acid is associated with an increased risk of hypertension, cardiovascular disease and chronic kidney disease. Hyperuricemia raises the risk of insulin resistance and metabolic syndrome including diabetes. Aim To find the association between purine metabolites and diabetic complications in rats. Materials and methods Alloxan was administered to induce diabetes in rats. After 30 days, the levels of uric acid, inosine, xanthine, hypoxanthine and AMP were assessed in both plasma and liver tissues using HPLC technique. Results A significant increase in xanthine, hypoxanthine, AMP levels (p < .001 and t-value 2.78) and inosine in plasma and liver tissues (p < .05 and t-value 2.11) with a concomitant increase in uric acid levels (p < .001 and t-value 2.80) was observed in diabetic group. Conclusion Purine metabolites like uric acid and other intermediate products of purine metabolism are increased in diabetes. These results can be used in addition or separately in evaluating the progression of diabetes.

Potential impact of auxin in modulation of insulin resistance in diabetic rats

The rational of this study to find out the impact of auxins in prevention of diabetic complications in rats. Seventy-five rats were randomly grouped into five groups: Group I; control (n = 15). (Groups 2–5, 60 rats) were received a single dose of STZ i.p, at dose of 65 mg/kg for induction diabetes. Group II; diabetic untreated. Group III; Rats were given auxin subcutaneous (2.5 µg/kg b.w). Group IV; rats were given auxin (5 µg/kg b.w). Group V; rats were injected insulin (5 units/kg b.w/day) as positive control. Treatment of diabetic rats with auxin (2.5 or 5 ug/kg b.w) for 8 weeks reversed the oxidant/antioxidant imbalance. The protective effect of auxin due to defence against oxygen free radicals production in retinal tissue. Also, auxin inhibit formation of AGEs and inhibit release of inflammatory mediators. It was concluded that, auxin may be used as promising therapeutic agents against diabetic complications.