Alloxan-induced Diabetic Model Research Articles

Platelet-Rich Plasma (PRP) Mitigates Kidney Dysfunction in Alloxan-Induced Diabetic Mice via Modulation of Renal Iron Regulatory Genes.

Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.

Furan-based chalcone protects β-cell damage and improves glucose uptake in alloxan-induced zebrafish diabetic model via influencing Peroxisome Proliferator-Activated Receptor agonists (PPAR-γ) signaling

Diabetes mellitus, a major global health concern, is emerging as the primary human disease in the twenty-first century, with beta cell damage and dysfunction playing a critical role, particularly in type 2 diabetes. Inflammation and oxidative stress are critical in beta cell damage associated with type 2 diabetes. Current anti-diabetic drugs frequently fail to achieve intended efficacy and are associated with side effects, necessitating novel treatments that target the underlying pathophysiology. Chalcones have gained popularity due to their varied biological activity. In this study, we use an alloxan-induced beta cell damage zebrafish model to evaluate the potential anti-inflammatory and beta cell protective properties of DKO3 ((E)-1-(5-methylfuran-2-yl)-3-(3-nitrophenyl) prop-2-en-1-one), a synthetic chalcone. DKO3 exhibits dose-dependent anti-inflammatory and α-glucosidase activity in vitro. DKO3 reduced oxidative stress, restored antioxidant enzyme levels, decreased lipid peroxidation and cellular damage, inhibited cellular apoptosis, and regulated proinflammatory cytokine levels. It prevented alloxan-induced beta cell damage, increased PPAR-γ expression, and influenced insulin-sensitive genes such as SIRT1, GLUT2, GSK3, and INSA. These findings underscore DKO3's potential therapeutic utility in managing diabetes and related inflammatory conditions.

Effect of Mucuna cochinchinensis seed extract on Alloxan-Induced Diabetic Experimental Rats

Objective: Mucuna cochinchinensis (Fabaceae)is a widely grown twiner that has been used in the traditional medicine for treating many ailments. The objective of the present study was to evaluate the hypoglycemic effects of ethyl acetate extract of M. cochinchinensis seeds on alloxan-induced diabetic rat models. Materials and Methods: M.cochinchinensis seeds were collected and macerated with ethyl acetate to obtain ethyl acetate extract of M. cochinchinensis (EMC). The obtained extract was subjected to preliminary phytochemical analysis using standard protocol and HPLC-MS study to identify the phytoconstituents present. Effect of EMC on parameters like blood glucose and plasma insulin levels were assessed using commercial kits in alloxan-induced experimental rats. Results: Preliminary phytochemical analysis of EMC showed the presence of alkaloids, flavonoids, terpenoids, saponins, tannins and glycosides. HPLC-MS study revealed the presence of 6-C-Pentosyl-8-C-hexosyl apigenin and kaempferol-3-O-rutinoside in EMC. EMC effect on alloxan-induced diabetic ratsblood glucose level on 1st, 7th and 14th day and plasma insulin levels were determined and was found to revert the blood glucose levels significantly (p<0.01). Conclusion: To conclude, EMC has potent efficacy in normalizing blood glucose and serum insulin concentration in alloxan induced diabetic rats.

Exogenous and endogenous nitric oxide eluting polylactic acid-based nanofibrous scaffolds for enhancing angiogenesis of diabetic wounds

Delayed wound healing is a major complication that diabetic patients suffer from due to high microbial infection susceptibility, high diabetic wound alkalinity, a low lymphangiogenesis rate, and a high inflammation rate, resulting in severe gangrene. Hence, this study aims to develop a multifunctional adhesive nanofibrous patch to promote the wound healing process. Phenytoin, sildenafil citrate, and/or nitric oxide-eluting nanoparticles were incorporated separately within the polylactic acid nanofibrous layer. Polylactic acid was fabricated in the form of highly porous nanofibrous matrices that resemble the natural structure of skin tissues in order to act as scaffolds that help cell migration and proliferation. A polylactic acid nanofibrous layer incorporating phenytoin was designed to stimulate fibroblast proliferation and inhibit inflammation. Another polylactic acid nanofibrous layer was loaded either with nitric oxide-eluting nanoparticles or sildenafil as a pro-angiogenic layer that can supply tissues with nitric oxide gas either exogenously or endogenously, respectively. The developed nanofibrous layers were in-vitro evaluated through different physicochemical, mechanical, and biological approaches. Finally, the efficiency of the prepared single multilayered patch was tested using an in-vivo alloxan-induced diabetic rats' model, which proved that the patches were able to release the incorporated cargos in a controlled manner, enhancing the wound healing process.

Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats via down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.

This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined. The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC50: 1.60 mg/ml) and α-amylase inhibition (IC50: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results. Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.

Medical Ozone Treatment Alleviate Blood Oxidative Stress And Pancreas Damage In an Alloxan-Induced Diabetes Model in Rats

Diabetic mellitus (DM ) is a prevalent systemic disease affecting a human and animals. The effects of diabetes are devastating and well documented. The increased production and/or ineffective scavenging of reactive oxygen species (ROS) may play a critical role in the development of diabetic complications. Therefore, it seems reasonable that antioxidants can play an important role in the improvement of diabetes. So, use medical ozone to study if it can regulate the oxidative complications of DM .The study was carried out on forty eight albino females rats included six groups Group I (Control) : 8 female rats were injected IP with citrate buffer (0.1 M, pH 5) daily for 6 weeks ,Group II (MO ): 8 female rats were injected IP 1.1 mg/kg b.w of MO daily for 6 weeks ,Group III (DM): 8 female rats induce diabetes by injection IP with freshly prepared alloxan 150 mg/kg b.w in citrate buffer (pH 5), Group IV(DM+MO): 8 diabetic female rats were injected IP 1.1 mg/kg b.w of MO daily for 6 weeks, group V(DM + Insulin): 8 diabetic female rats were injected subcutaneously 0.75 IU/100 g b.w. of Insulin daily for 6 weeks ,Group VI(DM +MO +Insulin):8diabetic female rats were injected IP 1.1 mg/kg b.w of MO and Insulin injected subcutaneously at a dose of 0.75 IU/100 g b.w , respectively daily for 6 weeks. experimental study parameters include antioxidant enzymes assay and histology the study for pancreas.

ANTI-DIABETIC ACTIVITY OF KABAU SEED POWDER SUSPENSION (ARCHIDENDRON BUBALINUM (JACK) I. C. NIELSEN) IN ALLOXAN-INDUCED DIABETIC RATS

Objective: The study was to optimize the method of test dosage form kabau seed simplicia suspension in alloxan-induced diabetic rat models.
 Methods: Simplisia powder sizing was carried out using three sieve sizes through meshes of 80, 120, and 200. Making a suspension of kabau seed powder is carried out using two methods, with the addition of CMC, which has been developed first and the powder is added with CMC, which is then developed and then homogenized. The study consisted of six groups, dosage given of 250, 500, and 1000 mg/kg BW. Blood glucose levels were determined by the GOD-PAP, phytochemical screening and TLC tests were carried out on the test material. The data were tested statistically using One Way ANOVA.
 Results: The powdered crude material with a particle size of 74 microns, obtained by sieving through a mesh size of 200, is utilized as the test material in the second method. An effective dose of 1000 mg/kg BW with a decrease in blood sugar levels by 132±13 mg/dl. Phytochemical screening contained alkaloids, flavonoids, phenolics, monoterpenes and sesquiterpenes, steroids, quinones and saponins. TLC of the test material, mobile phase used in TLC was toluene: chloroform: ethyl acetate (4:5:1), obtained 6 spots which gives a specific spot after being sprayed with the chromogenic reagent.
 Conclusion: powder with a particle size of 74 microns was used as the test material, using the second method. The effective dose as an antidiabetic is 1000 mg/kg BW with a reduction in blood sugar levels of 132.7±13 mg/dl.

In vivo acute toxicity, antidiabetic and antiulcer activities of polysaccharide from Linum usitatissimum L. seeds

The present study investigated acute oral toxicity, antidiabetic and antiulcer effects of the polysaccharide extracted from linseeds mature and ripe (Linum usitatisimum L., Family: Liliaceae). The acute oral toxicity (in vivo) of linseed polysaccharide was examined in Albino Wistar rats. In vivo antidiabetic activity and antiulcer activity were evaluated in Albino Wistar rats by alloxan-induced diabetic model and ethanol-induced ulcer model, respectively. The effects of linseed polysaccharide administered at 250 mg/kg of body weight dose on fasting blood glucose, body weight, lipid levels and histopathology of the treated pancreas were evaluated. The effects of linseed polysaccharide administered at 250 mg/kg of body weight dose on ulcer index, gastric secretion (gastric juice, pH, free acidity, and total acidity), macroscopic and histopathology analyses of treated gastric mucosa were evaluated. The acute oral toxicity results did not indicate any indication of toxicity associated with the administration of linseed polysaccharide to the treated rats. Linseed polysaccharide exhibited significant hypoglycaemic benefits in comparison to glibenclamide, which was treated as the positive control. In addition, linseed polysaccharide exhibited good gastroprotective properties with a significant improvement in inhibition percentage. Therefore, the results of the present study presented a clear demonstration of the potential uses of linseed polysaccharide as an adjuvant therapy for the management of diabetes mellitus and gastric ulcers.

Physicochemical characterization, phytochemical analysis, and pharmacological evaluation of Sambucus wightiana

Sambucus wightiana (SW) is a 4–5-foot herbaceous stem with 5–9 leaflets and pinnatifid leaves (15–30 cm). It is used to treat stomach disorders, as an emetic for expelling poisonous substances, and as a laxative for controlling skin diseases. Phytochemical research based on ethnopharmacological knowledge is frequently regarded as an appropriate approach for discovering new agents from higher-altitude plants. Therefore, the present study focussed on identifying, collecting, and authenticating the S. wightiana and, isolating and characterizing the phytoconstituents using the DPPH method, reducing power, total flavonoid, phenolic content, anti-hyperglycemic and antioxidant capacity. Furthermore, the evaluation of antidiabetic studies of extracts/fraction and pure phytoconstituents of S. wightiana in alloxan-induced diabetic model and OGTT methods were carried out. The observed results revealed that the methanolic extract of Sambucus wightiana has significant anti-hyperglycemic and anti-oxidant activity. The methanolic extracts of S. wightiana, a dose of alloxan/SW-400 mg/Kg (111.55 ± 6.9 mg/dl) also decreased significantly the serum ALP level (p < 0.05). The methanol extracts of S. wightiana showed highly significant anti-hyperglycemic activity (p < 0.05). From the methanolic extracts, alloxan/SW-400 mg/Kg (89.55 ± 2.5 mg/dl) showed highly significant decrease in serum LDL level (p < 0.05) in extract-treated groups, not changing the body weight substantially and methanolic extract of S. wightiana at a dose of 400 mg/Kg exhibited substantial lipid, and blood glucose levels and liver enzymes lowering capacity compared to the diabetic control group. Consequently, the prevention of hyperglycaemia by various other drugs, S. wightiana could contribute to a new formulation with significant pharmacological effects.

Evaluation of Antidiabetic Effect of Combined Leaf and Seed Extracts of Moringa oleifera (Moringaceae) on Alloxan-Induced Diabetes in Mice: A Biochemical and Histological Study.

Moringa oleifera (Moringaceae) is a medicinal plant rich in biologically active compounds. The aim of the present study was to screen M. oleifera 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 M. oleifera in an alloxan-induced diabetic model in mice. Our results suggest the potential for developing a natural potent antidiabetic drug from M. oleifera; however, clinical studies are required.

Assessment of the antidiabetic potential of extract and novel phytoniosomes formulation of Tradescantia pallida leaves in the alloxan-induced diabetic mouse model.

Diabetes inflicts health and economic burdens on communities and the present antidiabetic therapies have several drawbacks. Tradescantia pallida leaves have been used as a food colorant and food preservative; however, to our knowledge antidiabetic potential of the leaves of T. pallida has not been explored yet. The current study aimed to investigate the antidiabetic potential of T. pallida leaves extract and its comparison with the novel nisosome formulation of the extract. The leaves extract and phytoniosomes of T. pallida in doses of 15, 25 and 50 mg/kg were used to assess the oral glucose loaded, and alloxan-induced diabetic mice models. The biological parameters evaluated were; change in body weight, blood biochemistry, relative organ to body weight ratio and histopathology of the liver, pancreas and kidney. Results revealed that the extract 50 mg/kg and phytoniosomes 25 and 50 mg/kg remarkably reduced the blood glucose level in all hyperglycemic mice by possibly inhibiting α-amylase and α-glucosidase production. Body weight and blood biochemical parameters were considerably improved in phytoniosomes 50 mg/kg treated group. The relative body weight was similar to those of healthy mice in extract 50 mg/kg, phytoniosomes 25 mg/kg, and phytoniosomes 50 mg/kg treated groups. Histopathology showed the regeneration of cells in the CHN50 treated group. Hyphenated chromatographic analysis revealed potent metabolites, which confirmed the antidiabetic potential of the extract by inhibiting α-amylase and α-glucosidase using in silico analysis. The present data suggested that phytoniosomes have shown better antidiabetic potential than crude extract of these leaves.

Dental Composites with Magnesium Doped Zinc Oxide Nanoparticles Prevent Secondary Caries in the Alloxan-Induced Diabetic Model.

Antibacterial restorative materials against caries-causing bacteria are highly preferred among high-risk patients, such as the elderly, and patients with metabolic diseases such as diabetes. This study aimed to enhance the antibacterial potential of resin composite with Magnesium-doped Zinc oxide (Mg-doped ZnO) nanoparticles (NPs) and to look for their effectiveness in the alloxan-induced diabetic model. Hexagonal Mg-doped ZnO NPs (22.3 nm diameter) were synthesized by co-precipitation method and characterized through ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) analysis. The Mg-doped ZnO NPs (1, 2.5 and 5% w/w) were then evaluated for antibacterial activity using a closed system in vitro biofilm model. Significant enhancement in the antibacterial properties was observed in composites with 1% Mg-doped ZnO compared to composites with bare ZnO reinforced NPs (Streptococcus mutans, p = 0.0005; Enterococcus faecalis, p = 0.0074, Saliva microcosm, p &lt; 0.0001; Diabetic Saliva microcosm, p &lt; 0.0001). At 1-2.5% Mg-doped ZnO NPs concentration, compressive strength and biocompatibility of composites were not affected. The pH buffering effect was also achieved at these concentrations, hence not allowing optimal conditions for the anaerobic bacteria to grow. Furthermore, composites with Mg-doped ZnO prevented secondary caries formation in the secondary caries model of alloxan-induced diabetes. Therefore, Mg-doped ZnO NPs are highly recommended as an antibacterial agent for resin composites to avoid biofilm and subsequent secondary caries formation in high-risk patients.

Wound healing and anti-inflammatory effects of recombinant human angiogenin

New effective wound healing agents are a priority for modern clinical pharmacology. A promising approach would be to develop medicinal products that promote angiogenesis, which is a critical step in wound healing. The aim of the study was to evaluate the wound healing effect of a medicinal product based on recombinant human angiogenin in gel form in various experimental models. Materials and methods: white outbred male rats were used as experimental ani mals. The study compared healing effects of a regenerating product containing recombinant human angiogenin (0.0025%) in gel form and a reference product in full-thickness excision, incision, and burn wound models. The healing effect of the test product in treating chronic wounds was assessed in a model of alloxan-induced diabetes mellitus. The anti-inflammatory effect of the test product containing recombinant human angiogenin was compared with that of another reference product in a model of adjuvant-induced arthritis. Results: according to the study, the test product based on recombinant human angiogenin exerts higher wound healing effect in treating excision, incision, and burn wounds than the reference product (Solcoseryl gel). Being applied, the test product intensifies tissue repair in chronic wounds in the model of alloxan-induced diabetes. The dissociation of necrotic tissues and the progression towards epithelialisation at wound edges are more rapid. The anti-inflammatory effect of the test product based on recombinant human angiogenin is comparable with that of the reference product (Diclofenac gel). Conclusions: the test product based on recombinant human angiogenin in gel form was found to have pronounced wound healing and anti-inflammatory effects comparable with those of reference products.

Protective Effects of Zingiberis Carbonisata-Based Carbon Dots on Diabetic Liver Injury in Mice

To explain the active components of ZRC-CDs from the perspective of nanomaterials and investigate the potential mechanism for the treatment of diabetic liver injury, the structure, electron transfer properties, and elemental composition of ZRC-CDs were characterized. The protective effects of ZRC-CDs on the diabetic liver injury were demonstrated using the Alloxan-induced diabetic model. The ZRC-CDs are spherical, with a diameter ranging from 1.0–4.5 nm and a yield of 0.56%. The results showed that ZRC-CDs decreased the levels of blood glucose in diabetic mice and had a mitigating effect on elevated ALT and AST. More studies found that ZRC-CDs were able to decrease the levels of inflammatory cytokines and suppress the protein expression in related signaling pathways.

Antidiabetic Activity of Medicinal Plants: An Updated Overview of Streptozotocin and Alloxan-Induced Diabetic Models

Antidiabetic Activity of Medicinal Plants: An Updated Overview of Streptozotocin and Alloxan-Induced Diabetic Models

In Vitro and In Vivo Antidiabetic Activity, Phenolic Content and Microscopical Characterization of Terfezia claveryi.

Terfezia claveryi (T. claveryi) is used by traditional healers in the Middle East region to treat several diseases, including diabetes. The present study evaluated the total phenolic and investigated the blood-glucose-lowering potential of different aqueous extracts of this selected truffle using in vitro and in vivo models. The phytochemical profile was examined using UPLC-MS. The macerate and the microwave-assisted extract were the richest in phenolic compounds. All T. claveryi extracts exhibited a remarkable α-glucosidase inhibitory effect in vitro, with an IC50 of 2.43, 3.26, 5.18 and 3.31 mg/mL for the aqueous microwave-assisted extract macerate, infusion and decoction, respectively. On the other hand, in the high-fat diet alloxan-induced diabetic mice model, all tested crude aqueous extracts exhibited a significant antihyperglycemic activity (p < 0.05). Four hours after the administration of the 250 mg/kg dose, the macerate was able to induce a 29.4% blood-glucose-lowering effect compared to a 24.8% reduction induced by the infusion, which was sustained for a further two hours. The hypoglycemic effect (29.3% and 32.4%) was also recorded six hours after the administration of the single dose 500 mg/kg of the macerate and the infusion, respectively. Truffle extracts exhibited antidiabetic activity both in vitro and in vivo, providing a rationale for the traditional use as a natural hypoglycemic.

Pharmacological evaluation of the hypoglycemic and anti- Alzheimer’s activities of aerial parts of Breynia distachia (Phyllanthaceae)

Purpose: To determine the cytotoxic, bronchorelaxant, spasmolytic, antidiabetic, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, α-chymotrypsin and lipoxygenase inhibitory attributes of methanol and dichloromethane extracts of the aerial parts of Breynia distachia.Methods: The dichloromethane and methanol extracts of the aerial parts of the plant were prepared by maceration. Various ex vivo assays were employed, such as the brine shrimp lethality assay, lipoxygenase inhibitory activity assay, α-glucosidase inhibitory assay and α-chymotrypsin assay, as well as assays to assess the spasmolytic and bronchorelaxant activity. Meanwhile, the hypoglycaemic effect were analysed using an alloxan-induced diabetic model in Wistar albino rats.Results: The methanol extract (aerial) showed significant (p ≤ 0.05) cytotoxicity towards brine shrimp larvae at concentrations of 10, 100 and 1,000 μg/mL, respectively, whereas the dichloromethane extract (aerial) of the plant showed non-significant (p ≥ 0.05) results. The methanol extract (aerial parts) also demonstrated significant (p ≤ 0.05) α-glucosidase inhibitory activity and lipoxygenase inhibitory activity, with IC50 (half-maximal inhibitory concentration) values of 40.37 ± 5.29 μg/mL and 132.9 ± 0.33 μg/mL, respectively, while the dichloromethane extract exhibited significant (p ≤ 0.05) α-glucosidase inhibitory activity, with an IC50 value of 135.43 ± 8.29 μg/mL. An in vivo antidiabetic model showed that the administration of 150 and 300 mg/kg methanol extract of the aerial parts significantly (p ≤ 0.05) lowered the blood glucose level in alloxan-induced diabetic rats compared to control (treated with water).Conclusion: Data from different in vitro and in vivo models suggest that the methanol extract (aerial parts) of B. distachia shows significant cytotoxic, bronchorelaxant, spasmolytic, antidiabetic and anti-Alzheimer’s activity Hence, these findings validate the folkloric use of B. distachia and highlight the need to further explore its medicinal potential and the phytoconstituents responsible for its pharmacological actions.

Enhanced circulation longevity and pharmacodynamics of metformin from surface-modified nanostructured lipid carriers based on solidified reverse micellar solutions

Metformin hydrochloride (MTH) has been associated with poor/incomplete absorption (50–60%), low bioavailability, short half-life (0.4–0.5 h), high dosage and dose-related side effects. To overcome these barriers and improve oral bioavailability and efficacy of MTH, surface-modified nanostructured lipid carriers (NLCs) were developed. Lipid matrices composed of rational blends of beeswax and Phospholipon® 90H (as solid lipids) and Capryol-PGE 860 (as liquid lipid) were prepared by fusion, and the resultant lipid matrices were PEGylated to give 10, 20 and 40% PEGylated lipid matrices. MTH-loaded non-PEGylated and PEGylated NLCs were prepared via high-shear hot homogenization and characterized regarding particle properties and physicochemical performance. The encapsulation efficiencies (EE%) and loading capacities (LC) of the MTH-loaded NLCs were determined while the in vitro drug release was evaluated in phosphate buffered saline (PBS, pH 7.4). Antidiabetic and pharmacokinetics properties of the NLCs were ascertained in an alloxan-induced diabetic rats model after oral administration. The MTH-loaded NLCs were nanomeric (particle size: 184.8–882.50 nm) with low polydispersity index (0.368–0.687) and zeta potential (26.5–34.2 mV), irregular shape, amorphous nature with reduced crystallinity. The EE% and LC were >90 % and 16%, respectively. The formulations showed >65 % release over 12 h in a greater sustained manner than marketed MTH formulation (Glucophage®) as well as enhanced pharmacokinetics properties and sustained blood glucose lowering effect, even at reduced doses with PEGylated NLCs than Glucophage®. Thus, PEGylated NLC is a promising approach for improved delivery and oral bioavailability of MTH thus encouraging further development of the formulation.

Hypoglycemic effect of leaf extract of Pseuderanthemum crenulatum leaves in an alloxan-induced diabetic mice

In this study, the hypoglycaemic effects of ethanol extracts from Pseuderanthemum crenulatum leaves were investigated. The evaluated trials included: in vitroα-glucosidase inhibitory activity; oral glucose tolerance test in normoglycemic mice; hypoglycemia in an alloxan-induced diabetic mice model, and oral toxicity assay. The results showed that the ethanol extract of P. crenulatumleaves was able to inhibit α-glucosidase enzyme at IC50=66.01 μg/ml, 1.8 times higher than acarbose control (IC50 was 122.2 μg/ml). After 21 days of using leaf extract of P. crenulatum (1 g/kg) to treat diabetic mice, the blood glucose was reduced by 42.02%. This result was equivalent to gliclazide (10 mg/kg) which reduced the blood glucose of diabetic mice by 41.78%. The oral toxicity test results at a dose of 5 g/kg equivalent to 357 g of fresh leaf/kg after 72 hours was not exhibited acute oral toxicity in mice. In summary, there is a need for more studies on the ability of P. crenulatum leaves to treat diabetes.

ALTERATIONS OF ANTIOXIDANT ENZYMES DURING ALLOXAN-INDUCED DIABETES (EXPERIMENTAL STUDY)

Our study aimed to assess the activity of the blood antioxidant system in the animal model of alloxan-induced diabetes in rats.Diabetes in rats was induced diabetes by a single intraperitoneally injection of freshly prepared 12% aqueous alloxan solution ( 200 mg/kg). The glucose level was measured after 1, 2, 3, 10, 15, and 30 days from alloxan administration. The study included only those rats with blood glucose levels above 250 mg/dl on the 2nd day after alloxan administration.We investigated the activity of antioxidant enzymes, superoxide dismutase (SOD) and catalase (Cat) in the blood serum.The results of the studies show that the activity of enzymatic antioxidant systems in rats' blood sharply increased during the first 3 days after injection of alloxan. That may be due to the compensatory reaction of the body in response to alloxan-induced oxidative stress. Afterwards, the activity of SOD and Cat decreased, which may be due to the utilization of antioxidant proteins in the detoxification process of ROSs, their glycation and decreased level of the protein synthesis in the body at the intensive hyperglycemia and oxidative stress conditions.