-
Molecules (Basel, Switzerland) Apr 2023Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and has been found to be an inhibitor of α-glucosidase,...
Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.
Topics: Rats; Animals; Hypoglycemic Agents; Alloxan; Berberis; Glycated Hemoglobin; Diabetes Mellitus, Experimental; Plant Extracts; Blood Glucose; Glucose; Insulin; Hypolipidemic Agents
PubMed: 37110767
DOI: 10.3390/molecules28083533 -
Experimental Biology and Medicine... Jan 2017The aim of this study was to investigate the anti-hyperglycemic activity and mechanism of formononetin in alloxan-induced type 1 diabetic mice by determining its effect...
The aim of this study was to investigate the anti-hyperglycemic activity and mechanism of formononetin in alloxan-induced type 1 diabetic mice by determining its effect on some diabetes-related indices as described below. Body weight, fasting blood glucose, hepatic glycogen, serum insulin, and serum glucagon were determined by electronic scales, glucometer, and ELISA kits. Fas, Caspase-3, pancreatic and duodenal homeobox-1 , insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase and glucose-6-phosphatase mRNA, and proteins levels in liver tissue were detected by fluorogenic quantitative-polymerase chain reaction and Western blot assays. The results indicated that formononetin (5, 10, and 20 mg/kg; oral administration) reversed the alloxan-induced increase of some indices (fasting blood glucose level and Fas and Caspase-3 mRNA and proteins levels in pancreas tissue) and reduction of some indices (body weight gain, oral glucose tolerance, insulin activity, hepatic glycogen level, pancreatic and duodenal homeobox-1, insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase mRNA and protein levels in liver tissue). The glucagon level and glucose-6-phosphatase mRNA and protein levels in liver tissue were not affected by the drugs administration. In conclusion, formononetin exhibited anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice by inhibiting islet B cell apoptosis and promoting islet B cell regeneration, insulin secretion, hepatic glycogen synthesis, and hepatic glycolysis.
Topics: Alloxan; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Disease Models, Animal; Glucagon; Hypoglycemic Agents; Insulin; Islets of Langerhans; Isoflavones; Liver; Liver Glycogen; Male; Mice
PubMed: 27412955
DOI: 10.1177/1535370216657445 -
Ethiopian Journal of Health Sciences May 2023Diabetes mellitus is among the most prevalent and costly chronic diseases in the world. Unfortunately, immediate prospects for a cure are not available. We aimed to...
BACKGROUND
Diabetes mellitus is among the most prevalent and costly chronic diseases in the world. Unfortunately, immediate prospects for a cure are not available. We aimed to determine the in vivo antidiabetic activity, histologic, and biochemical effect of Balanites aegyptiaca fruit extract on alloxan-induced diabetes in Wistar rats.
METHODS
Thirty-six Wistar rats were allotted into six groups (n=6). Group I was normal control. Group II was induced with diabetes but not treated.Groups III-V were induced with diabetes and treated with 100, 200, and 300 mg/kg extracts while Group VI was treated with Metformin once daily for 14 days. Animals were euthanized, and blood samples were collected for biochemical assays. The liver, kidney, pancreas, and testis were excised and processed by the paraffin wax method.
RESULT
Oral administration of BA extract significantly (P<0.05) reduced blood glucose, liver enzymes, and creatinine levels in diabetic animals. The extract also improved the body weights of diabetic animals and microscopic anatomy of the pancreas, testis, liver, and kidney parenchyma compared to the control.
CONCLUSION
Balanites aegyptiaca phytochemicals reduced blood glucose level and improved the histology of the liver, kidney, pancreas, and testis. Further study is recommended to identify the phytochemicals and mechanism of action.
Topics: Rats; Male; Animals; Rats, Wistar; Balanites; Alloxan; Plant Extracts; Blood Glucose; Fruit; Diabetes Mellitus, Experimental
PubMed: 37576166
DOI: 10.4314/ejhs.v33i3.7 -
Biomedicine & Pharmacotherapy =... Dec 2018Diabetic nephropathy (DN) is considered as one of the major microvascular complications of diabetes mellitus (DM) which leads to end stage renal disease (ESRD). Even...
Diabetic nephropathy (DN) is considered as one of the major microvascular complications of diabetes mellitus (DM) which leads to end stage renal disease (ESRD). Even though existing therapeutic options are effective in decreasing albuminuria, drugs targeting the preservation of GFR and prevention of ESRD may provide better strategy for the treatment. Since metabolic disorders are multifactorial, poly-herbal medications, and drug-herbal combination are in demand. Therefore, the present work is focused on the combinatorial renoprotective effect of rutin and ramipril on alloxan induced DN in experimental rats. Male Wistar rats were divided into five groups, group I-control, group II-diabetic rats, group III-diabetic rats treated with ramipril, group IV-diabetic rats treated with rutin, group V-diabetic rats treated with ramipril and rutin for a period of six weeks. Results revealed administration of alloxan induced hyperglycemia and alteration in antioxidant profile. However, combination of a bioflavonoid with an Angiotensin converting enzyme (ACE) inhibitor administration restored the antioxidant status in experimental DN rats. Over-expression of ACE, TGF-β1 and decreased podocin expression in diabetic rats was significantly reversed in rats administered with both ramipril and rutin. In addition to attentuating oxidative stress and fibrosis, combinatorial therapy significantly down-regulated endoplasmic reticulum stress markers GRP78 and CHOP. Notably, combination of both ramipril and rutin in low doses reduced the side effects than the administration of monotherapy alone. Histopathological results revealed that combinatorial therapy was associated with a reduction in tubulointerstitial injury. The current study contributes the understanding of the multifactorial nature of DN and implies combinatorial treatment of ACE inhibitor with an antioxidant will be a promising therapeutic strategy for DN by their mechanism of action targeting various pathophysiological changes and stress pathways.
Topics: Alloxan; Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Drug Therapy, Combination; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Male; Oxidative Stress; Peptidyl-Dipeptidase A; Ramipril; Rats; Rats, Wistar; Rutin; Transcription Factor CHOP; Transforming Growth Factor beta1
PubMed: 30372836
DOI: 10.1016/j.biopha.2018.09.142 -
Nutrients Feb 2016Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary to reduce cardiovascular events. Honey reduces...
Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary to reduce cardiovascular events. Honey reduces hyperglycemia and dyslipidemia. The reproducibility of these beneficial effects and their generalization to honey samples of other geographical parts of the world remain controversial. Currently, data are limited and findings are inconclusive especially with evidence showing honey increased glycosylated hemoglobin in diabetic patients. It was hypothesized that this deteriorating effect might be due to administered high doses. This study investigated if Nigerian honey could ameliorate hyperglycemia and hyperlipidemia. It also evaluated if high doses of honey could worsen glucose and lipid abnormalities. Honey (1.0, 2.0 or 3.0 g/kg) was administered to diabetic rats for three weeks. Honey (1.0 or 2.0 g/kg) significantly (p < 0.05) increased high density lipoprotein (HDL) cholesterol while it significantly (p < 0.05) reduced hyperglycemia, triglycerides (TGs), very low density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, coronary risk index (CRI) and cardiovascular risk index (CVRI). In contrast, honey (3.0 g/kg) significantly (p < 0.05) reduced TGs and VLDL cholesterol. This study confirms the reproducibility of glucose lowering and hypolipidemic effects of honey using Nigerian honey. However, none of the doses deteriorated hyperglycemia and dyslipidemia.
Topics: Alloxan; Animals; Biomarkers; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Dyslipidemias; Honey; Lipids; Nigeria; Rats, Wistar; Risk Assessment; Risk Factors
PubMed: 26927161
DOI: 10.3390/nu8030095 -
Biomedical and Environmental Sciences :... Sep 2020To evaluate the efficiency of silymarin (SMN) in modulating metabolic parameters and redox status in rats with type 1 diabetes mellitus (T1DM).
OBJECTIVE
To evaluate the efficiency of silymarin (SMN) in modulating metabolic parameters and redox status in rats with type 1 diabetes mellitus (T1DM).
METHODS
Diabetes was induced by intraperitoneal injection of alloxan. The diabetic rats were administered with SMN at doses of 50 and 100 mg/kg body weight/d for 30 consecutive days. The rats were divided into the following four groups: vehicle control, diabetic (alloxan-treated), DS50 (alloxan + 50 mg/kg body weight/d of SMN), and DS100 (alloxan + 100 mg/kg body weight/d of SMN) groups. The bodyweight and food and water intake were evaluated. After 30 d, the animals were euthanized and the blood was collected for measuring the serum levels of glucose, triacylglycerol (TAG), urea, and creatinine. The liver and pancreas were collected for measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of carbonylated protein (PC). The pancreas sample was also used for histological analysis.
RESULTS
SMN reduced hepatic ( < 0.001) and pancreatic ( < 0.001) protein damage and creatinine levels ( = 0.0141) in addition to decreasing food ( < 0.001) and water intake ( < 0.001). However, treatment with SMN did not improve beta-cell function or decrease blood glucose levels in diabetic rats.
CONCLUSION
SMN improved polyphagia and polydipsia, renal function, and protected the liver and pancreas against protein damage without affecting hyperglycemia in diabetic animals.
Topics: Alloxan; Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Liver; Oxidation-Reduction; Pancreas; Protective Agents; Silymarin
PubMed: 33106214
DOI: 10.3967/bes2020.090 -
The Biochemical Journal Dec 2000Alloxan is used to induce diabetes in animals; however, the underlying mechanisms are still a matter of debate. Alloxan evoked a rapid hyperpolarization of the plasma...
Alloxan is used to induce diabetes in animals; however, the underlying mechanisms are still a matter of debate. Alloxan evoked a rapid hyperpolarization of the plasma membrane potential and suppressed electrical activity elicited by 15 mM glucose, thus terminating voltage-dependent Ca(2+) influx. Accordingly, glucose-induced oscillations in intracellular free Ca(2+) concentration were abolished. The effect of alloxan on membrane potential could not be reversed by glucose but was reversed by tolbutamide. However, the sensitivity to tolbutamide was decreased after treatment of the cells with alloxan. These effects closely resemble those described earlier for H(2)O(2). H(2)O(2) and alloxan decreased the mitochondrial membrane potential, indicating a decrease in ATP production and thus interference with cell metabolism. A decrease in ATP synthesis would explain the plasma membrane hyperpolarization observed in intact islets, reflecting the activation of ATP-dependent K(+) channels. Surprisingly, alloxan inhibited the whole-cell K(+)(ATP) current measured in single cells and the single-channel K(+)(ATP) current registered in excised patches. This inhibitory effect of alloxan is not mediated by changes in cell metabolism but seems to be due to direct interactions with the K(+)(ATP) channels via thiol-group oxidation. We have monitored the appearance of reactive oxygen species in single cells and islets treated with alloxan and H(2)O(2) for comparison. In contrast to H(2)O(2), alloxan induced the appearance of measurable reactive oxygen species only in islets but not in single cells. The results show that alloxan evokes different effects in islets and single cells, giving a possible explanation for inconsistent results reported in the past. It is concluded that alloxan exerts its diabetogenic effect by the production of H(2)O(2) in intact islets.
Topics: Alloxan; Animals; Calcium; Calcium Channels; Female; In Vitro Techniques; Islets of Langerhans; Membrane Potentials; Mice; Patch-Clamp Techniques; Reactive Oxygen Species
PubMed: 11085932
DOI: No ID Found -
Bioelectrochemistry (Amsterdam,... Oct 2020The dielectric properties of the eye lens were studied for healthy and alloxane-induced diabetic rabbits in the frequency range from 500 Hz to 100 kHz electric field...
The dielectric properties of the eye lens were studied for healthy and alloxane-induced diabetic rabbits in the frequency range from 500 Hz to 100 kHz electric field and temperatures from 25 to 50 °C. In the full temperature range, the average relative permittivity and dielectric loss values for a healthy lens are lower than those recorded for diabetic tissue. Dielectric relaxation of polar amino acids on the alpha-crystallin surface with a characteristic frequency of 7 kHz in the range of 25-50 °C for healthy and diabetic samples is accompanied by the activation energy of proton conductivity with an average values of 33 and 39 kJ mol, respectively. The permittivity decrement, which characterizes the size of the dielectric dispersion with a central relaxation time of 0.023 ms for a diabetic sample, is more than twice as high as for a healthy sample. Measurements on the rabbit eye lens were carried out at ambient temperature above and below the physiological range, since these conditions provide an appropriate pattern of dielectric behavior for the diagnosis of clinical dysfunction of the human lens.
Topics: Alloxan; Animals; Diabetes Mellitus, Experimental; Electric Impedance; Lens, Crystalline; Rabbits; alpha-Crystallins
PubMed: 32544783
DOI: 10.1016/j.bioelechem.2020.107583 -
Oxidative Medicine and Cellular... 2023() is a medicinal plant rich in biologically active compounds. The aim of the present study was to screen methanolic leaf (L) extract, seed (S) extract, and a combined...
() is a medicinal plant rich in biologically active compounds. The aim of the present study was to screen methanolic leaf (L) extract, seed (S) extract, and a combined leaf/seed extract (2L : 1S ratio) for antidiabetic and antioxidant activities in mice following administration at a dose level of 500 mg/kg of body weight/day. Diabetes was induced by alloxan administration. Mice were treated with the extracts for 1 and 3 months and compared with the appropriate control. At the end of the study period, the mice were euthanized and pancreas, liver, kidney, and blood samples were collected for the analysis of biochemical parameters and histopathology. The oral administration of the combined L/S extract significantly reduced fasting blood glucose to normal levels compared with L or S extracts individually; moreover, a significant decrease in cholesterol, triglycerides, creatinine, liver enzymes, and oxidant markers was observed, with a concomitant increase in antioxidant biomarkers. Thus, the combined extract has stronger antihyperlipidemic and antioxidant properties than the individual extracts. The histopathological results also support the biochemical parameters, showing recovery of the pancreas, liver, and kidney tissue. The effects of the combined L/S extracts persisted throughout the study period tested. To the best of our knowledge, this is the first study to report on the antidiabetic, antioxidant, and antihyperlipidemic effects of a combined L/S extract of in an alloxan-induced diabetic model in mice. Our results suggest the potential for developing a natural potent antidiabetic drug from ; however, clinical studies are required.
Topics: Mice; Animals; Hypoglycemic Agents; Antioxidants; Moringa oleifera; Alloxan; Plant Extracts; Diabetes Mellitus, Experimental; Hypolipidemic Agents; Plant Leaves; Seeds
PubMed: 37215365
DOI: 10.1155/2023/9136217 -
BioMed Research International 2022Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of...
Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably ( < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated ( < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly ( < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated ( < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM.
Topics: Alloxan; Animals; Antioxidants; Blood Glucose; Cardiotoxicity; Citrus; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Ethanol; Hypoglycemic Agents; Plant Extracts; Rats; Rats, Wistar
PubMed: 35757467
DOI: 10.1155/2022/2807337