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Journal of Advanced Pharmaceutical... 2024Diabetes mellitus is a chronic condition defined by elevated blood sugar levels (hyperglycemia). This condition can lead to complications such as nephropathy, which is...
Diabetes mellitus is a chronic condition defined by elevated blood sugar levels (hyperglycemia). This condition can lead to complications such as nephropathy, which is histologically shown with glomerulosclerosis. Glucomannan, a component of , offers numerous health benefits, but its direct therapeutic effect on glomeruli remains uncertain. Male Wistar rats which were taken with random sampling ( = 30) were distributed into six distinct groups. All groups, excluding Group N, received 125 mg/kg BW single intraperitoneal dose of alloxan. Group N received a single dose of PBS 125 mg/kg BW. After 7 days, Group K + was induced with acarbose at a dose of 50 mg/70 kg BW (adjusted using a factor of 0.018) orally per day. Groups N and K - induced with 1% CMC Na at 0.2 mL/0.1 kg orally per day. While Group P1, P2, and P3 were orally given ethanolic extract orally per day at a dose of 100, 200, and 400 mg/kg BW. The following 50 days of treatment, the Wistar rats were euthanized, and their kidney was preserved for histological slides that were stained with hematoxylin and eosin. The oral administration of ethanolic extract in alloxan-induced diabetic rats led to a significant decrease in the average of glomerulosclerosis instances when compared to the K - group. The most effective dose was observed at 400 mg/kg BW per day. administration leads to a reduction in glomerulosclerosis occurrences, suggesting its potential as a therapeutic approach for reducing complications probability linked to hyperglycemia.
PubMed: 38903556
DOI: 10.4103/JAPTR.JAPTR_426_23 -
Frontiers in Physiology 2024Herein, we obtained and characterized deltaN p63- and adenosine triphosphate-binding cassette subfamily G member 2-expressing limbal stem cells (LSCs). Chitosan and...
Herein, we obtained and characterized deltaN p63- and adenosine triphosphate-binding cassette subfamily G member 2-expressing limbal stem cells (LSCs). Chitosan and carboxymethyl chitosan (CTH) were cross-linked to be an in situ thermosensitive hydrogel (ACH), which was printed through four-dimensional (4D) printing to obtain a porous carrier with uniform pore diameter (4D-CTH). Rabbits were injected with alloxan to induce diabetes mellitus (DM). Following this, the LSC-carrying hydrogel was spread on the surface of the cornea of the diabetic rabbits to cure corneal epithelium injury. Compared with the control group (LSCs only), rapid wound healing was observed in rabbits treated with LSC-carrying 4D-CTH. Furthermore, the test group also showed better corneal nerve repair ability. The results indicated the potential of LSC-carrying 4D-CTH in curing corneal epithelium injury. 4D-CTH holds potential as a useful tool for studying regenerative processes occurring during the treatment of various diabetic corneal epithelium pathologies with the use of stem cell-based technologies.
PubMed: 38887317
DOI: 10.3389/fphys.2024.1285850 -
Animal Models and Experimental Medicine Jun 2024Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by... (Review)
Review
Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by hyperglycemia, a condition involving a high blood glucose level brought on by deficiencies in insulin secretion, decreased activity of insulin, or both. Prolonged effects of diabetes include cardiovascular problems, retinopathy, neuropathy, nephropathy, and vascular alterations in both macro- and micro-blood vessels. In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis, identifying targets, and reviewing novel treatment options and medications. Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences. The most popular in vivo studies involves the small animal models, such as rodent models, chemically induced diabetogens like streptozotocin and alloxan, and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals. Other models include virally induced models, diet/nutrition induced diabetic animals, surgically induced models or pancreatectomy models, and non-obese models. Large animals or non-rodent models like porcine (pig), canine (dog), nonhuman primate, and Zebrafish models are also outlined. The in vitro models discussed are murine and human beta-cell lines and pancreatic islets, human stem cells, and organoid cultures. The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition of α-glucosidase activity.
PubMed: 38837635
DOI: 10.1002/ame2.12442 -
Biomedicine & Pharmacotherapy =... Jul 2024Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a...
Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT, 5-HT, 5-HT and 5-HT receptor agonists, respectively). Blocking 5-HT receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT and 5-HT activation.
Topics: Animals; Succinates; Male; Diabetes Mellitus, Experimental; Rats, Wistar; Kidney; Sympathetic Nervous System; Rats; Serotonin 5-HT2 Receptor Antagonists; Serotonin; Diabetic Nephropathies; Vasoconstriction
PubMed: 38820974
DOI: 10.1016/j.biopha.2024.116814 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024Oxidative stress accumulation becomes a pathophysiological factor in diabetic neuropathy (DN), activating TRPV-1. Resveratrol in cocoa pod husk exhibits antioxidant...
Oxidative stress accumulation becomes a pathophysiological factor in diabetic neuropathy (DN), activating TRPV-1. Resveratrol in cocoa pod husk exhibits antioxidant activity that could be beneficial in DN. This study examined how the ethanol extract of cocoa pod husk (EECPH) affects DN in mice by targeting TRPV-1. Cocoa pod husk was extracted using 96 % ethanol with remaceration. The antioxidant activity was measured using DPPH. Mice were induced using alloxan 210 mg/kg BW i.p. At day 14, mice were randomized into seven groups: normal, diabetic, gabapentin 100 mg/kg BW, metformin 250 mg/kg BW, and EECPH (doses 250, 500, and 750 mg/kg BW). Treatments were administered orally, once daily for 14 days. The latency time and blood glucose levels were measured on days 7, 14, 21, and 28. On day 29, mice were sacrificed, and the blood, pancreas, and spinal cord were removed. Malondialdehyde, cholesterol, and serum glutamic oxaloacetic/pyruvic transaminase (SGOT/PT) were examined. Morphology of the spinal cord and pancreas was determined using hematoxylin and eosin staining. The expression of TRPV-1 was assessed using immunohistochemistry. he EECPH dose of 750 mg/kg BW showed the greatest effect in lowering hyperalgesia and blood glucose as well as cholesterol and SGOT/PT in mice. That dose also improved the histology of the pancreas and spinal cord by altering the expression of TRPV-1. It can be concluded that EECPH may lower the expression of TRPV-1 in the pancreas and spinal cord of mice. This activity was responsible of reducing hyperalgesia in DN mice.
PubMed: 38746850
DOI: 10.1016/j.jsps.2024.102097 -
Forensic Science International Jul 2024Most recommended methods for visualising fingermarks on paper rely on chemical developers that target and react with amino acids. Traditionally, these developers are...
Most recommended methods for visualising fingermarks on paper rely on chemical developers that target and react with amino acids. Traditionally, these developers are sprayed onto paper substrates in solutions of per- and polyfluoroalkyl substances (PFAS), but now those same PFAS chemicals are undergoing phaseout or phasedown, which threatens to undermine forensic capabilities. This situation provides an opportunity to pivot towards greener approaches to fingermark visualisation. The ideal methodology would be a water-based treatment, as these provide superior safety for practitioners, combined with environmental sustainability. A major hurdle to implementing a water-based fingermark developer targeting amino acids is that water, as a universal solvent, can dissolve the eccrine components in fingermarks, as well as any optical or luminescent dyes that are created, causing the ridge detail to run or dissolve. This work circumvents this problem by delivering the amino acid developer alloxan in a hydrogel, which enables sharp fingermark ridge details to be observed despite it being a water-based treatment. Alloxan dissolved in a viscous hydrogel is shown here to react with the amino acids in fingerprint residues to form the coloured dye murexide, supported by optimisation and characterisation studies.
Topics: Dermatoglyphics; Humans; Hydrogels; Amino Acids; Water; Coloring Agents; Solvents
PubMed: 38703405
DOI: 10.1016/j.forsciint.2024.112045 -
Scientific Reports Apr 2024The present study predicts the molecular targets and druglike properties of the phyto-compound piperine (PIP) by in silico studies including molecular docking...
The present study predicts the molecular targets and druglike properties of the phyto-compound piperine (PIP) by in silico studies including molecular docking simulation, druglikeness prediction and ADME analysis for prospective therapeutic benefits against diabetic complications. PIP was encapsulated in biodegradable polymer poly-lactide-co-glycolide (PLGA) to form nanopiperine (NPIP) and their physico-chemical properties were characterized by AFM and DLS. ∼ 30 nm sized NPIP showed 86.68% encapsulation efficiency and - 6 mV zeta potential, demonstrated great interactive stability and binding with CT-DNA displaying upsurge in molar ellipticity during CD spectroscopy. NPIP lowered glucose levels in peripheral circulation by > 65 mg/dL compared to disease model and improved glucose influx in alloxan-induced in vivo and in vitro diabetes models concerted with 3-folds decrease in ROS production, ROS-induced DNA damage and 27.24% decrease in nuclear condensation. The 25% increase in % cell viability and inhibition in chromosome aberration justified the initiation of p53 and PARP DNA repairing protein expression and maintenance of Hsp90. Thus, the experimental study corroborated well with in silico predictions of modulating the p53/PARP-1/Hsp90 axis, with predicted dock score value of - 8.72, - 8.57, - 8.76 kcal/mol respectively, validated docking-based preventive approaches for unravelling the intricacies of molecular signalling and nano-drug efficacy as therapeutics for diabetics.
Topics: Tumor Suppressor Protein p53; Poly (ADP-Ribose) Polymerase-1; HSP90 Heat-Shock Proteins; Animals; Piperidines; Benzodioxoles; Polylactic Acid-Polyglycolic Acid Copolymer; Molecular Docking Simulation; Hyperglycemia; Alkaloids; Polyunsaturated Alkamides; Diabetes Mellitus, Experimental; Alloxan; Rats; Humans; Male; Reactive Oxygen Species; Mice; Nanoparticles; DNA Damage
PubMed: 38664520
DOI: 10.1038/s41598-024-60208-1 -
Cureus Mar 2024Background Diabetes mellitus is a complex metabolic disorder characterized by oxidative stress and impaired glycemic control. This study investigates the therapeutic...
Background Diabetes mellitus is a complex metabolic disorder characterized by oxidative stress and impaired glycemic control. This study investigates the therapeutic potential of and diets in diabetic Wistar rats and assesses their impact on oxidative stress markers and blood glucose levels. Methods In this experiment, eight groups of six male Wistar rats (n = 12.5%), aged 8 to 12 weeks, were carefully set up to see how different treatments for diabetes and oxidative stress affected the two conditions. The random selection process was implemented to minimize any potential bias and ensure that the results of the study would be representative of the general population of Wistar rats. The groups were as follows: a nondiabetic control group (NDC) served as the baseline, while diabetes was induced in the alloxan monohydrate group (150 mg/kg). Another group was given the standard drug metformin (M, 100 mg/kg), and two control groups that did not have diabetes were given extracts of (TC, 340 mg/kg) and (CS, 200 mg/kg). Three groups of diabetic rats were given a mix of these treatments. and extracts were given at set doses (TC, 340 mg/kg; CS, 200 mg/kg), along with 150 mg/kg of a drug that causes diabetes. Over a 21-day period, oxidative stress parameters such as glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione reductase (GSHrd) levels, and blood glucose were carefully measured to check for signs of oxidative stress and diabetes progression Results Considerable differences in GSH levels were noted across the groups, with the highest GSH concentration found in the group treated with the inducing drug, while the lowest GSH levels were observed in the diabetic group that was administered both and C (p < 0.001). MDA levels also varied, with the diabetic group treated with having the highest MDA concentration (3.54 ± 0.29 μmol/L) and the nondiabetic control group treated with exhibiting the lowest MDA levels (1.66 ± 0.08 μmol/L; p < 0.001). SOD activity was highest in the standard drug group and lowest in the diabetic group treated with . GSH activity was notably higher in the diabetic groups that received dietary interventions (p < 0.001). Blood glucose levels showed diverse responses, with the standard drug group experiencing a substantial reduction, while the inducing drug group exhibited a consistent increase. Conclusion The study highlights the significant impact of dietary interventions with and on oxidative stress markers and blood glucose regulation in diabetic Wistar rats. These findings suggest a potential role for these dietary components in mitigating oxidative stress and improving glycemic control in diabetes, although further research is warranted to elucidate the underlying mechanisms and clinical implications.
PubMed: 38606255
DOI: 10.7759/cureus.55985 -
Drug Design, Development and Therapy 2024The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of...
INTRODUCTION
The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats.
METHODS
The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances.
RESULTS & DISCUSSION
The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.
Topics: Rats; Animals; Hypoglycemic Agents; Structure-Activity Relationship; Imidazoline Receptors; Diabetes Mellitus, Experimental; Ursodeoxycholic Acid; Benzimidazoles; Sugars; Molecular Docking Simulation; Molecular Structure
PubMed: 38585255
DOI: 10.2147/DDDT.S447289 -
Cureus Mar 2024Diabetes mellitus (DM), a prevalent metabolic disorder, is associated with widespread damage to bodily systems, notably causing significant dysfunction within the...
Diabetes mellitus (DM), a prevalent metabolic disorder, is associated with widespread damage to bodily systems, notably causing significant dysfunction within the peripheral and central nervous systems (CNS). The primary objective of this study is to explore the extent of DM's impact on cognitive and behavioral functions and to evaluate the therapeutic potential of ethanol leaf extracts from (ZJ) and (EA) in mitigating these adverse effects. Utilizing an established animal model, we aimed to determine the effectiveness of these plant extracts in ameliorating the cognitive impairments commonly seen in diabetic states. In our experimental framework, we allocated Wistar rats (n=6 per group) into eight different groups, inducing DM through alloxan administration. The intervention groups were treated orally with either the standard antidiabetic drug glibenclamide or varying doses of ZJ and EA extracts over periods of seven and 21 days. Throughout the study, we carefully tracked fluctuations in blood glucose levels, noting considerable decreases, particularly following the 21-day treatment interval. Post-treatment, the rats' cognitive functions were assessed using the Morris water maze (MWM) test. This evaluation revealed significant cognitive enhancement in the diabetic rats administered with ZJ and EA extracts, with these groups displaying reduced latency in finding the submerged platform, indicative of improved learning and memory. These observations were statistically significant (p<0.01). The findings underscore the hypoglycemic effects of ZJ and EA extracts and suggest their viability as cognitive enhancers in the context of DM. The protective effects of these extracts against cognitive decline caused by DM are clear. They add important new information to the research on natural phytochemicals for managing chronic diseases. This study opens new avenues for the application of these substances in treating neurocognitive disorders associated with DM.
PubMed: 38562322
DOI: 10.7759/cureus.55400