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In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, were investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

The fabrication of polymeric micro/nanofibers is gaining attention due to their use in an array of applications including tissue engineering scaffolds, nanosensors, and fiber-reinforced composites. Despite their versatile nature, polymeric fibers are widely underutilized due to the lack of reliable, large-scale production techniques. Upon the discovery of centrifugal spinning and, recently, pressurized gyration techniques, new research directions have emerged. Here, we report a comprehensive study detailing the optimal conditions to significantly improve the morphology, homogeneity, and yield of fibers of varying diameters. A series of polymeric fibers was created using a 21 wt.% solution of polyethylene oxide in distilled water and the fluid behavior was monitored inside a transparent reservoir using a high-speed camera. Fabrication of the fibers took less than 1 s. Using centrifugal spinning, we studied the formation of the fibers at three different rotational speeds, and for pressurized gyration, one rotational speed was studied with three different nitrogen gas pressures. Using the pressurized gyration technique at a gas pressure of 0.3 MPa, there was significant improvement in the production yield of the fibers. We found a strong correlation between the variation of pressure and the rate of the solution leaving the reservoir with the improved morphology of the fibers. The use of reduced power techniques, like centrifugal spinning and pressured gyration, to yield high-quality nonwoven nanofibers and microfibers in large quantities is important due to their use in rapidly expanding markets. (C) 2019 Author(s).

Thymus praceox and Salvia triloba possess anti-inflammatory and anti-diabetic effects on type 2 diabetic ratsBackground: Thymus praceox subsp. skorpilii var. skorpilii is a species of Thymus, from Lamiaceae and have proven antioxidant effect. T.vulgaris and T.cramanicus, other thymus species, have shown antidiabetic effects in previous studies (1).In addition, previous studies have reported that salvia species have antioxidant, anti-inflammatory and hypoglycemic effects. Salvia triloba is a subspecies of Lamiaceae and there is no study have demonstrated its antidiabetic effect. The pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance are associated with inflammation as a result of immun system activation. Additionally, oxidative stress has influence cytokine mediated inflammation. Adipose tissue has been shown to act as an endocrine gland through the release of adipokines such as adiponectin, leptin and adipsin; implicated in physiological functions such as insulin sensitivity, appetite modulation and inflammatory response. Moreover, some studies suggested that adipokines may be the target molecules for treatment of T2DM. Adipose tissue caused to elevation of insulin resistance due to the indication of cytokine production which leads to inflammation in diabetic individuals (2).Aim: This study was designed to investigate the effects of Thymus praceox and Salvia triloba on adiponectin and inflammation which play roles for pathogenesis of T2DM. Furthermore, to evaluate the severity of anti-inflammatory effect, new researches will be designed regarding this study.Method: Sprague Dawley rats (200-300 g) were injected streptozotocin (STZ)/nicotinamide(NA) intraperitoneally (i.p.) to induce T2DM model. After 72 hours injection, blood glucose levels were measured and more than 200 mg/dl were determined as diabetic. Blood samples were collected weekly to determine postprandial blood glucose levels. Before starting diabetes study effective doses of Thymus praceox subsp. skorpilii var. skorpilii methanolic extract (100 mg/kg) and Salvia triloba methanolic extract (200 mg/kg) acquired from oral glucose tolerance test in normal rats. Treatments started after three days of diabetes induction and administered daily. Rats are divided into 5 groups; diabetes group, 1th therapy group, 2nd therapy group , positive control group (therapy with metformin) and control group. On day 21, all rats were decapitated and blood samples were taken for evaluating tumor necrosis factor alpha (TNF-u03b1), interleukin-6 (IL-6), interleukin-1u03b2 (IL-1u03b2), interleukin-10 (IL-10) and adiponectin levels by ELISA.Results: TNF-u03b1, IL-6 and IL-1u03b2 are pro-inflammatory cytokines and their levels increased in diabetes group compared to control group while these levels decreased in therapy groups and positive control group in this study. Controversially, adiponectin and the anti-inflammatory cytokine IL-10 levels decreased in diabetes group compared to control group while Salvia triloba extract and Thymus praceox extract prevented the decreases of IL-10 and adiponectin. At the end of experiment, it was demonstrated that both Thymus praceox extract and Salvia triloba extract performed a significant fall in blood glucose level with 58% and 45%, (p

Abstract Title: The inhibitory effects of Salvia triloba and Thymus praecox on acetylcholinesterase activity in diabetic ratsBackgroundDiabetes mellitus (DM) is a metabolic disease characterized by long-term complications including cerebrovascular injury and cognitive disorders. Acetylcholinesterase (AChE) which is involved in numerous pathways in the central nervous system regulates the level of acetylcholine (ACh) which plays vital functions such as memory, learning, modulation of cerebral blood flow, movement control, neurotransmission as well (1). Recent studies have shown that hypoinsulinemia and insulin resistance is the reason of the decreased level of ACh and contribute the possible biochemical link between DM and cognitive disorders including Alzheimeru2019s disease. Studies with plants have shed light on the correction of cognitive functions of diabetes mellitus with increased AChE activity. Some Salvia and Thymus species of the Lamiaceae family have antidiabetic effects (2). There is no study on antidiabetic activity of Salvia triloba and Thymus praecox.AimTo investigate the effects of Salvia triloba and Thymus praecox on brain acetylcholinesterase activities in diabetes mellitus. With the help of obtained results, further studies will be carried out for ameliorating cognitive dysfunction effectively and also supporting current treatments.MethodThe rats were divided into five groups (6 rats per group): Group-I: Normal control, Group-II: Diabetic control, Group-III: Treatment with Salvia triloba methanolic extract, (200 mg/kg/day, i.g.), Group-IV: Treatment with Thymus praecox methanolic extract, (100mg/kg/day, i.g.), Group-V: Treatment with Metformin (400 mg/kg/day, i.g.). Type 2 DM was induced experimentally in these groups of rats by the intraperitoneal administration of 55 mg/kg of STZ and 100 mg/kg nicotinamide, except control group. Treatments were carried out after induction of DM and lasted for 3 weeks except decapitation day. The AChE enzymatic assay was determined according to the method of Ellman et al. The reaction mixture (2 mL final volume) contained 100 mM K+-phosphate buffer, pH 7.5 and 1 mM 5,50-dithiobisnitrobenzoic acid (DTNB). The method is based on the formation of the yellow anion, 5, 50- dithio-bis-acid-nitrobenzoic, measured by absorbance at 412 nm during 2 min incubation at 25u00b0C. The enzyme (40u201350 mg of protein) was pre-incubated for 2 min. The reaction was initiated by adding 0.8 mM acetylthiocholine iodide (AcSCh). All samples were in triplicate readings and the enzyme activities were expressed in mmol AcSCh/h/mg of protein.ResultsThymus praecox and Salvia triloba in methanolic extract considerably decreased (pu02c20.0001) blood glucose levels compared to diabetic rats and performed this drop for 3 weeks. Thymus praecox extract reached its maximum hypoglycemic effect (141.83u00b17.31, pu02c20.0001) in 2 weeks. At the same time, Thymus praecox and Salvia triloba extract also showed strong hypoglycemic effect (164.83u00b113.30, pu02c20.0001). The diabetic group exhibited a significant increase (pu02c20.001) in AChE activity in prefrontal cortex compared to the control and the treatment groups. However Salvia triloba extract and Thymus praecox extract reverted this increase (pu02c20.001) in AChE activity induced by diabetes after 3 weeks of treatment. The metformin group decreased (%47, pu02c20.001) in AChE activity compared to diabetic groups. Salvia triloba extract (%37, pu02c20.001) and Thymus praecox extract group (%41, pu02c20.001) a considerably decrease in AChE activity compared to diabetic group. The metformin group did not show a significant difference in enzyme activity compared to the control group. However, Salvia triloba and Thymus praecox increased (pu02c20.05) in AChE activity compared to control groups.DiscussionOur study results showed that an increase in AChE activity in type 2 diabetic rat brains. This increase in AChE activity in the T2DM rat model can be linked to depletion in cholinergic actions leading to defective neurotransmission and cognitive dysfunction as a result of decreased levels of ACh in the synaptic cleft. We showed that the reestablishment of AChE activity by Salvia triloba extract and Thymus praecox extract which for the first time demonstrated antidiabetic activities can contribute to the maintenance of cholinergic signaling in diabetic rats. In the light of the results, these plants give a valuable direction for researchers on the future for diabetes-related cognitive disorders. 1. Jacobson AM., et al., Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group, Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356(18):1842u20131852.2. Davids D., et al., Ethnobotanical survey of medicinal plants used to manage High Blood Pressure and Type 2 Diabetes Mellitus in Bitterfontein, Western Cape Province, South Africa, J Ethnopharmacol. 2016 Dec 24;194:755-766.

Forming polymeric core–sheath nanofibers is gaining prominence owing to their numerous potential applications, most notably in functional scenarios such as antiviral filtration, which is attracting significant attention due to the current COVID pandemic. This study has successfully designed and constructed a novel pressurized gyration vessel to fabricate core–sheath polymer nanofibers. Several water-soluble and water-insoluble polymer combinations are investigated. Both polyethylene oxide and polyvinyl alcohol were used as the core while both poly(lactic acid) (PLA) and poly(caprolactone) (PCL) were used as the sheath; PLA and PCL were used as core and sheath, in different instances; respectively. The fluid behavior of the core–sheath within the vessel was studied with and without applied pressure using computational fluid dynamics to simulate the core–sheath flow within the chamber. A high-speed camera was used to observe the behavior of jetted solutions at core–sheath openings, and the best scenario was achieved using 6000 rpm spinning speed with 0.2 MPa (twice atmospheric) applied pressure. The surface morphology of core–sheath fibers was studied using a scanning electron microscope, and focused ion beam milling assisted scanning electron microscopy was used to investigate the cross-sectional features of the produced fibers. Laser confocal scanning microscopy was also used to verify the core–sheath structure of the fibers, which were further characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Thus, using a variety of polymer combinations, we show, both theoretically and experimentally, how core–sheath fibers evolve in a vessel that can serve as a scalable manufacturing pressurized gyration production process.

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.

Wound dressings made from natural polymers are an important aspect of biomaterials. Protein-based materials are less likely to instigate an immunogenic response and have the capacity to degrade in vivo, also without triggering an inflammatory response. Therefore, gelatin (GEL) was chosen and combined with bacterial cellulose (BC) to produce nanofibres and the potential of an all-natural polymer construct was determined. GEL and BC were successfully electrospun with metformin (Met) and glybenclamide (Gb) using a portable, point of need electrospinning set up. The virgin fibre group exhibited a significant effect on the proliferation of L929 (mouse fibroblast) cells but all fibre samples can safely be applied on wound site without risk of cytotoxicity. According to the results obtained by animal tests, the GEL-BC-Gb group showed better recovery than the GEL-BC-Met group. Diabetic wounds treated with GEL-BC-Met were characterized by moderate re-epithelialization and partially organized granulation tissue. Moderate to complete re-epithelialization and well-formed granulation tissue were observed in diabetic wounds treated with GEL-BC-Gb. The histologic scores obtained on day 14 confirmed that the GEL-BC-Gb group played a stronger wound-healing role compared to the GEL-BC-Met group. The highest decrease of TNF-α level was observed in the GEL-BC-Gb group at the end of the experiment but there is no significant difference between drug-loaded fibre groups. Therefore, topical administration of Met and Gb in a sustained release form has a high potential for diabetic wound healing with high bioavailability and fewer systemic side effects but Gb showed better improvement according to the results of the animal tests.

In Turkey, Helichrysum genus is represented by 26 taxa belonging to 20 species in Turkish flora of which 14 ones are endemic to Turkey. The aerial parts of Helichrysum plicatum subsp. plicatum are used kidney stones, kidney and stomach ailments. The extraction procedures and solvents are important step in processing of bioactive constituents from the plant materials. Therefore, the aim of this study was to evaluate in vitro antioxidant, antimicrobial, anti-urease, anticholinesterase and in vivo anti-inflammatory activities of Helichrysum plicatum subsp. plicatum different extracts. In addition, the phenolic characterization of the Soxhlet and maceration methanol extracts which showed significant antioxidant, anti-urease, antimicrobial, anti-inflammatory and anticholinesterase activities were performed by HPLC-DAD and LC-MS/MS. In the present study, the Soxhlet methanol extract exhibited strong antioxidant, antimicrobial and anticholinesterase activities than other extracts. The maceration methanol extract showed the strongest anti-urease activity. The Soxhlet methanol and maceration methanol extracts showed in vivo anti-inflammatory activities very close to each other. As a result of this study, chlorogenic acid, dicaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, naringenin-O-hexoside and isoquercitrin compounds were analysed in plant. Therefore, it is thought that methanol extracts can be used as a natural source in the future for food and pharmaceutical industries.

Objective: Novel investigations have confirmed that hyperglycemia is strictly associated with the development of cognitive impairment and dementia. Sodium-dependent glucose transporter (SGLT) inhibitors, which are oral antidiabetic drugs, are currently being investigated as the medication in Alzheimer's disease (AD). In our study, Camellia sinensis (green tea), which inhibits sodium-dependent glucose transporter-1 (SGLT-1), was used in the treatment of type 2 diabetes mellitus (T2DM)-induced AD-like alterations via its antidiabetic effects.Methods: High-fat diet/streptozotocin-treated rat model was chosen to provide T2DM-induced AD-like alterations. Antidiabetic effects were evaluated with the measurement of blood glucose level (BGL), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT). On the other hand, novel object recognition test (NORT), open field test (OFT), passive avoidance test (PAT), and Morris’s water maze (MWM) test were performed to investigate the anti-Alzheimer's effects of C. Sinensis.Results: C. sinensis tolerated BGL for a short time but metformin, the first medication prescribed for T2DM, tolerated BGL during the test for 120 min. C. sinensis increased the number of square crosses and the frequency of grooming activity in a similar manner to metformin in OFT. C. sinensis treatment improved exploratory behavior and memory retention components in NORT. The step-through latency decreased in HFD/STZ-treated rat model but it improved with metformin and C. sinensis treatment in PAT. According to the results obtained by the MWM test, C. sinensis treatment slightly improved learning.Conclusion: C. sinensis improved short-term memory and increased the locomotor activity in rats according to the results obtained by NORT, OFT, and PA.

The purpose of this study was to comparatively reveal for the first time the antioxidant, anti-inflammatory effects of Phlomis pungens and Coridothymus capitatus methanol extracts obtained by using maceration extraction method. According to the results of anti-inflammatory activity, P. pungens methanolic extract demonstrated a more prominent and intensive antiinflammatory effect with 24.7% of inhibitive capacity in the altered edema size after the first hour of carrageenan injection compared to C. capitatus methanolic extract. P. pungens methanolic extract inhibitory effect increased during three hours and reached maximum by 41.9%. According to the results obtained from antioxidant activity experiments, methanol extract of C. capitatus exhibited stronger free radical scavenging (DPPH), cupric reducing (CUPRAC), ferric reducing/antioxidant power (FRAP) and ABTS radical cation scavenging activity than P. pungens extract. In additon, C. capitatus extract had higher ABTS radical cation scavenging and ferric reducing/antioxidant power activity than ascorbic acid, BHT and BHA, respectively. Therefore, this extract can be used in both medicine and food industry as a natural antioxidant source.

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p

Some Salvia and Thymus species of Lamiaceae family come into prominence with strong antidiabetic effects. Compared to the other species, there are limited studies on antidiabetic activity of Salvia triloba (ST) and Thymus praecox subsp. skorpilii var. skorpilii (TPS). The aim of this study was to adjust the dosage and to determine the antidiabetic effects of methanol extracts of ST and TPS in streptozotocin/nicotinamide-induced diabetic rats. Type II diabetes mellitus (T2DM) was induced by a single intraperitoneal (i. p.) injection of streptozotocin (STZ) dissolved in 0.1 M cold citrate buffer (pH 4.5) at a dose of 55 mg/kg/body weight (b.w.) and nicotinamide (100 mg/kg/b.w.) was given prior to STZ injection. For adjusting dosage, oral glucose tolerance test (OGTT) was used while insulin tolerance test (ITT), OGTT, blood glucose levels and animal weights were used to evaluate the antidiabetic effects of ST and TPS. According to the OGTT, the most effective doses for ST and TPS were 200 mg/kg and 100 mg/kg, respectively. At the end of three weeks, blood glucose levels of control goup reached to 462.50 mg/dl, whereas ST and TPS-treated groups blood glucose levels decreased less than 200.00 mg/dl. In conclusion, the present study suggests that both of ST and TPS methanolic extracts may be of therapeutic benefit in diabetes and thus need to further studies.