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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 Apr 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.
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 -
Journal of Pharmacopuncture Mar 2024The -derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by...
OBJECTIVES
The -derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2.
METHODS
Upon molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For validation of nephro-protective effects, were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted.
RESULTS
The study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group.
CONCLUSION
This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.
PubMed: 38560336
DOI: 10.3831/KPI.2024.27.1.1 -
Metabolism Open Mar 2024Diabetes mellitus (DM) is one of the leading worldwide public health problems. It is characterized by hyperglycemia which induces oxidative stress and inflammation, both...
Diabetes mellitus (DM) is one of the leading worldwide public health problems. It is characterized by hyperglycemia which induces oxidative stress and inflammation, both involved in the pathogenesis of diabetes. We previously showed that (BD) and (HS) extracts reduced hyperglycemia and hyperlipidemia in alloxan-induced diabetic rats. In the present study, we evaluated the antioxidant and anti-inflammatory activities of both plants in alloxan-induced diabetic rats. Two sets of experiments were conducted in male Wistar rats subjected to a single intraperitoneal injection of alloxan monohydrate (150 mg/kg, b. w.). Then, diabetic rats were daily administered with either BD (1st set of experiments) or HS (2nd set of experiments) at 100, 200, and 400 mg/kg orally for 21 consecutive days. Glibenclamide (10 mg/kg) was also administered as a reference drug. At the end of the study, the animals were anesthetized, and blood samples were collected from each animal. Then, oxidative stress and inflammatory biomarkers in the serum were determined. We found that treatment with BD and HS significantly reduced malondialdehyde (MDA) and enhanced the levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). These extracts also significantly decreased the inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). From the results obtained, it can therefore be concluded that BD and HS have the potential to being developed as natural sources of antioxidant and anti-inflammatory agents that can be used for the prevention or treatment of DM.
PubMed: 38455229
DOI: 10.1016/j.metop.2024.100278 -
Heliyon Feb 2024Poly-herbal therapies for chronic diseases like diabetes mellitus (DM) have been practiced in south Asia for centuries. One of such therapies comprises of Hordeum...
Poly-herbal therapies for chronic diseases like diabetes mellitus (DM) have been practiced in south Asia for centuries. One of such therapies comprises of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum that have shown encouraging therapeutic potential in the treatment of diabetes and obesity. Therefore, poly-herbal granules (PHGs) of this formula were developed and investigated for their anti-diabetic and anti-obesity potential in obese-diabetic rats. The developed PHGs were chemical characterized and the virtual molecular docking was performed by Discovery studio visualizer (DSV) software. For in-vivo experiment, obesity in rats was induced with high-fat high-sugar diet. After that, diabetes was induced by alloxan monohydrate 150 mg/kg i.p. injection. The diseased rats were treated with PHGs at 250, 500 and 750 mg/kg/day for four weeks. GC-MS analysis of PHGs demonstrated the presence of 1,3-Benzenedicarboxylic acid bis(2-ethylhexyl) ester and 1,2-Benzenedicarboxylic acid di-isooctyl ester and phenol, 2,4-bis(1,1-dimethylethyl). Molecular docking of these compounds demonstrated higher binding energies with receptor than metformin against α-amylase and α-glucosidase. PHGs exhibited a decline in body weight, HbA1c, hyperlipidemia, hyperglycemia, and insulin resistance in diseased rats. The histopathological examination revealed that PHGs improved the alloxan-induced damage to the pancreas. Furthermore, PHGs increased the SOD, CAT and GSH while and the decreased the level of MDA in the liver, kidney and pancreas of diseased rats. Additionally, the PHGs had significantly downregulated the TNF-α and NF-κB while upregulated the expression of NrF-2. The current study demonstrated that the PHGs exhibited anti-diabetic and anti-obesity potential through amelioration of oxidative stress, NF-κB, TNF-α, and NrF-2 due to the presence of different phytochemicals.
PubMed: 38384558
DOI: 10.1016/j.heliyon.2024.e26126 -
Journal of Advanced Veterinary and... Dec 2023Andaliman () is a potent medicinal plant in Asia. This present study aimed to reveal the effectivity of Andaliman fruit extract in alleviating hyperglycemia, sensory and...
OBJECTIVE
Andaliman () is a potent medicinal plant in Asia. This present study aimed to reveal the effectivity of Andaliman fruit extract in alleviating hyperglycemia, sensory and motoric balance disorders, histopathology of the cerebellum, and tissue oxidative stress in diabetic mice induced by alloxan.
MATERIALS AND METHODS
Diabetes induction was performed by intraperitoneally injecting alloxan monohydrate [200 mg/kg body weight (BW)]. Subsequently, the mice were treated daily with an ethanolic extract of Andaliman fruit (0, 150, 300, 450 mg/kg BW per oral) for 28 days, followed by measurements of blood glucose, paw sensitivity, motoric balance, histopathology of the cerebellum, and malondialdehyde (MDA) levels. Moreover, the phytochemical constituents of the extract were elucidated by liquid chromatography.
RESULTS
Higher doses of Andaliman fruit extract could significantly attenuate the elevation of random and fasting blood glucose ( < 0.05) and improve paw sensitivity responses ( < 0.05) and motoric balances ( < 0.05) in diabetic mice. Moreover, Andaliman fruit extract could significantly attenuate the degeneration of cerebellar Purkinje cells ( < 0.05) and suppress MDA levels in the blood ( < 0.05) while blunting the MDA in the brain tissue ( < 0.05). Phytochemical screening revealed 39 compounds in the Andaliman extract belonging to the groups of alkaloids (26 compounds), flavonoids (12 compounds), and terpenoids (1 compound).
CONCLUSION
The ethanolic extract of Andaliman fruit is capable of ameliorating diabetic neuropathy, motor balance disorders, and Purkinje cell degeneration while also reducing oxidative stress in the peripheral system. Hence, Andaliman extract is a promising candidate for formulation as an herbal remedy against the detrimental outcomes of diabetes mellitus.
PubMed: 38370902
DOI: 10.5455/javar.2023.j716