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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 -
Scientific Reports Feb 2024Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan...
Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.
Topics: Animals; Female; Male; Hypoglycemic Agents; Limonene; Zebrafish; Blood Glucose; Proton Magnetic Resonance Spectroscopy; Obesity; Diet, High-Fat; Hyperglycemia; Diabetes Mellitus
PubMed: 38360784
DOI: 10.1038/s41598-023-45608-z -
Molecules (Basel, Switzerland) Feb 2024(1) Background: The effect of Lindl. () on hyperglycemic syndrome has only been recently known for several years. Materials of were always collected from the plants...
(1) Background: The effect of Lindl. () on hyperglycemic syndrome has only been recently known for several years. Materials of were always collected from the plants cultivated in various growth ages. However, regarding the efficacy of on hyperglycemic syndrome, it was still unknown as to which cultivation age would be selected. On the other hand, with the lack of quality markers, it is difficult to control the quality of to treat hyperglycemic syndrome. (2) Methods: The effects of cultivated at year 1 and year 3 were checked on alloxan-induced diabetic mice while their body weight, diet, water intake, and urinary output were monitored. Moreover, levels of glycosylated serum protein and insulin were measured using Elisa kits. The constituents of were identified and analyzed by using UPLC-Q/trap. Quality markers were screened out by integrating the data from UPLC-Q/trap into a network pharmacology model. (3) Results: The cultivated at both year 1 and year 3 showed a significant effect on hyperglycemic syndrome at the high dosage level; however, regarding the significant level, from year 1 showed the better effect. In , most of the metabolites were identified as alkaloids and sesquiterpene glycosides. Alkaloids, represented by dendrobine, were enriched in from year 1, while sesquiterpene glycosides were enriched in from year 3. Twenty one metabolites were differentially expressed between from year 1 and year 3. The aforementioned 21 metabolites were enriched to 34 therapeutic targets directly related to diabetes. (4) Conclusions: Regarding the therapy for hyperglycemic syndrome, cultivated at year 1 was more recommended than that at year 3. Alkaloids were recommended to be used as markers to control the quality of for hyperglycemic syndrome treatment.
Topics: Animals; Mice; Hypoglycemic Agents; Dendrobium; Diabetes Mellitus, Experimental; Alkaloids; Glycosides; Sesquiterpenes
PubMed: 38338442
DOI: 10.3390/molecules29030699 -
Journal of Ayurveda and Integrative... 2024Malondialdehyde (MDA) is one of a dominat marker in oxidative stress condition, and when inflammation occurred tumor necrosis factor- α (TNF-α) played a significant...
BACKGROUND
Malondialdehyde (MDA) is one of a dominat marker in oxidative stress condition, and when inflammation occurred tumor necrosis factor- α (TNF-α) played a significant influence in the propagation this process. Purified gambier (Uncaria gambier Roxb.) contained 90% catechin which is proven to have antioxidant activity and may prevent unwanted inflammatory responses during diabetic state.
OBJECTIVE
The objective of this research was to assess how purified gambier affected plasma MDA and TNF- α levels in alloxan-induced diabetic rats.
MATERIAL AND METHODS
In this study, 35 rats were used. Alloxan 120 mg/kg BW intraperitoneal injection was administered to induce diabetes conditions in rats. All animals were divided into 5 groups, diabetic control group treated with vehicle, positive control group treated with glibenclamide dose 0.45 mg/kg BW), and treatment groups treated with purified gambier dose of 2.5; 5 and 10 mg/kg BW. All animals were treated respectively for 14 days. Plasma MDA and TNF- α levels were measured on day 3, and 14.
RESULTS
Two-way ANOVA was applied to analyze all of the data, these findings suggested that purified gambier has antioxidant-related anti-inflammation actions. possesses blood sugar-lowering activity (p<0.05). The plasma MDA and TNF- α level of treatment group were significantly reduced (p<0.05) compared to diabetes control group.
CONCLUSION
These results depicted that at doses of 2.5-10 mg/kg BW, purified gambier has antioxidant-associated anti-inflammation effects when given for 14 days on diabetic rat model by reducing plasma levels MDA and TNF-α.
PubMed: 38266537
DOI: 10.1016/j.jaim.2023.100855 -
Medical Ultrasonography Mar 2024To explore benefits of high-frame-rate contrast-enhanced ultrasonography (H-CEUS) for early kidney injury in a rabbit model of diabetic nephropathy (DN).
AIM
To explore benefits of high-frame-rate contrast-enhanced ultrasonography (H-CEUS) for early kidney injury in a rabbit model of diabetic nephropathy (DN).
METHODS
Diabetic rabbits were induced with alloxan administration and split into 2 groups with or without urinary microalbuminuria after a fatty and sugary diet: diabetic rabbits with nephropathy (Group A) and diabetic rabbits without nephropathy (Group B). The control group (Group C) comprised healthy rabbits. Renal H-CEUS and conventional CEUS (C-CEUS) imaging were conducted. Serum creatinine (SCR), blood urea nitrogen (BUN) and urinary microalbuminuria were measured.
RESULTS
SCR and BUN levels were barely changed in Groups B and C (p>0.05), whereas Group A exhibited a rise (p<0.05). Perfusion parameters of the two CEUS modalities showed reduced peak intensity (PI) and ascending slope (AS) and elevated area under the curve (AUC) and time to peak (TTP) in Group A versus Group B (p<0.05) and Group B versus Group C (p<0.05). The arrival time (AT) and descending slope (DS) exhibited little difference among the three groups. H-CEUS had a stronger correlation of perfusion parameters with SCR and BUN than C-CEUS.
CONCLUSIONS
H-CEUS outperforms C-CEUS in diagnosing early renal damage in DN. H-CEUS perfusion parameters demonstrate temporal superiority over routine laboratory indices.
Topics: Animals; Rabbits; Diabetic Nephropathies; Contrast Media; Kidney; Urinary Tract; Ultrasonography; Diabetes Mellitus
PubMed: 38244221
DOI: 10.11152/mu-4318