Fucoidan from Sargassum wightii reduces oxidative stress through upregulating Nrf2/HO-1 signaling pathway in alloxan-induced diabetic cardiomyopathy rats.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a form of cardiac dysfunction caused by diabetes, increasing heart failure and death. Studies shown that hyperglycemia-induced oxidative stress significantly affects heart structure and functional changes during diabetic cardiomyopathy. Fucoidans are sulfated polysaccharide derived from naturally available seaweeds and reported for various biological functions such as antioxidant, anti-diabetic, and anti-inflammatory. However, the therapeutic potential of Indian seaweeds against DCM remains largely unexplored. Therefore, the current study aimed to work on the cardioprotective effect of extracted fucoidan from Sargassum wightii (SwF) in alloxan-induced DCM. METHODS AND RESULTS: Diabetes (DM) was induced with alloxan monohydrate (150 mg/kg-1) dissolved in Nacl (0.9%) overnight-fasted rats. Group III, IV rats were DM induced, followed by treated with SwF (150 mg/kg-1) and (300 mg/kg-1). Group V and VI were non-diabetic rats and received SwF (150 mg/kg-1) and (300 mg/kg-1). SwF reduced classical progressive DM complications such as hyperglycemia, polydipsia, polyphagia, and polyurea in alloxan-induced diabetic rats. Biochemical analysis showed that SwF decreased blood glucose, cardiac markers enzymes, and lipid peroxidation levels compared to diabetic rats. SwF administration significantly increased Nrf2, HO-1, SOD, Catalase, and NQO1 gene expression. In addition, SwF-treated rats showed reduced heart tissue damage with increased Nrf2 and HO-1 protein expression. CONCLUSION: The current research concludes that targeting oxidative stress with SwF provided an effective role in the prevention of DCM. Thus, fucoidan could be used to develop functional food ingredients for DCM.

High-fat diet-induced nonalcoholic steatohepatitis is accelerated by low carnitine and impaired glucose tolerance in novel murine models.

Carnitine deficiency and impaired glucose tolerance (IGT) exacerbate liver steatosis. Given the current lack of ideal murine nonalcoholic steatohepatitis (NASH) models, we investigated new NASH models using jvs/+ mice with low carnitine and wild-type mice with low-dose alloxan-induced IGT. The jvs/+ and wild-type mice were divided into jvs/+ mice fed a high-fat diet (HFD) from 3 weeks of age (HF hetero group), wild-type mice with low-dose alloxan treatment fed HFD (AL + HF wild group), wild-type mice fed HFD (HF wild group), and two types of mice fed a normal diet-jvs/+ and wild-type (intact group). All mice were sacrificed at 20 or 40 weeks of age. All male HFD-fed mice showed obesity, IGT, high blood insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), high liver enzyme levels, and high cholesterol levels. The degree of IGT was the worst in the AL + HF wild group, and blood insulin levels and HOMA-IR score were remarkably increased from 20 to 40 weeks of age. Almost all HFD-fed mice showed steatosis, fibrosis, and lobular inflammation in the centrilobular zone. These changes were accompanied by hepatocyte ballooning and were enhanced at 40 weeks of age. Furthermore, the incidence rate of nodular hyperplasia and adenoma in both the HF hetero and AL + HF wild groups was nearly 30%. We successfully established two novel murine models of NASH using male jvs/+ mice with low carnitine and male wild-type mice with IGT that eventually developed obesity, fatty liver, insulin resistance, liver fibrosis, and tumorigenesis. These results suggest that low carnitine levels and early-stage induction of IGT are important factors in the progression of NASH to tumorigenesis, similar to human NASH.

ß-cells regeneration by WL15 of cysteine and glycine-rich protein 2 which reduces alloxan induced ß-cell dysfunction and oxidative stress through phosphoenolpyruvate carboxykinase and insulin pathway in zebrafish in-vivo larval model.

BACKGROUND: Pancreatic ß-cells are susceptible to oxidative stress, leading to ß-cell death and dysfunction due to enhanced ROS levels and type 2 diabetes. To inhibit the ß-cells damages induced by the oxidative stress, the present study investigates the beneficial effect of various peptides (WL15, RF13, RW20, IW13 and MF18) of immune related proteins (cysteine and glycine-rich protein 2, histone acetyltransferase, vacuolar protein sorting associated protein 26B, serine threonine-protein kinase and CxxC zinc finger protein, respectively). Also, the molecular mechanism of WL15 from cysteine and glycine-rich protein 2 on ß-cell regeneration was identified through PEPCK and insulin pathway. MATERIALS AND METHODS: In this study, a total of five peptides including WL15, RF13, RW20, IW13, and MF18 were derived from immune-related proteins such as cysteine and glycine-rich protein 2, histone acetyltransferase, vacuolar protein sorting associated protein 26B, serine threonine-protein kinase and CxxC zinc finger protein, respectively. These protein sequences were obtained from an earlier constructed transcriptome database of a teleost Channa striatus. The identified peptides were evaluated for their antioxidant as well as antidiabetic activity. Based on the in silico analysis and in-vitro screening experiments, WL15 was predicted to have better antioxidant and antidiabetic activity among the five different peptides. Therefore, WL15 alone was further analyzed for apoptosis, antioxidant capacity, glucose metabolism, and gene expression performance, which was investigated on the alloxan (500 µM) induced zebrafish in vivo larval model. RESULTS: The results showed alloxan exposure to zebrafish larvae for a day, the ROS was generated in the ß-cells. Interestingly, WL15 treatment showed a protective effect by reducing the toxicity of alloxan exposed zebrafish larvae by increasing their survival and heart rate. Moreover, WL15 reduced the intracellular ROS level and apoptosis in alloxan-induced larvae. The superoxide anion and lipid peroxidation levels are also reduced by improving the glutathione content after the WL15 treatment. Besides, WL15 treatment increased the proliferation rate of ß-cells and decreased the glucose level. Further, the gene expression studies revealed that WL15 treatment normalized the PEPCK expression while upregulating the insulin expression in alloxan exposed larvae. CONCLUSION: Overall, the findings indicate that WL15 of cysteine and glycine-rich protein 2 can act as a potential antioxidant for type 2 diabetes patients in respect of improving ß-cell regeneration.

Antidiabetic and pancreas-protective potential of Parthenium Hysterophorous (Carrot grass) in Alloxan induced diabetic rabbits.

Parthenium hysterophorus has been used to cure cancer, fever, malaria, diarrhea, dysentery, and neurologic disorders. This study evaluates the anti-diabetic effects of methanolic extract of P. hysterophorus (MEPH) in alloxan-induced diabetic rabbits. Twenty-five rabbits were divided into 5groups (N=5). Group-I served as a negative control. Groups II to V were injected with freshly prepared alloxan solution 150 mg/kg intraperitoneally to induce diabetes. Group II till V received following treatments orally: Group II: Alloxan 150 mg/kg alone; group III: Alloxan + MEPH (50 mg/kg); group IV: Alloxan + MEPH (100 mg/kg); group V: Alloxan +Glucophage (62.5 mg/kg), respectively for 10 days. The body weight of all animals was recorded on the 1st, 4th, 7th and 10th days. Short-term (1st, 3rd, 5th and 7th hour) and long-term (4th, 7th and 10th day) hypoglycemic effects were also recorded. All animals were sacrificed on the 10th day to isolate the pancreas for histopathological examination. The results showed that MPEH reduced the blood glucose levels in all the groups of alloxan-induced diabetic rabbits. The histopathological studies depicted that 100 mg/kg of MEPH most effectively repaired alloxan-induced pancreatic damage. The study showed that the MPEH is useful for developing effective phytomedicine to treat diabetes mellitus.

Evaluation of Safety of Stewart's Wood Fern (Dryopteris stewartii) and Its Anti-Hyperglycemic Potential in Alloxan-Induced Diabetic Mice.

Diabetes has become a critical challenge to the global health concerns. Cytotoxicity and development of resistance against available drugs for management of diabetes have shifted the focus of global scientific researchers from synthetic to herbal medications. Therefore, the current study was conducted to investigate the possible anti-hyperglycemic potential of Dryopteris stewartii using Swiss albino mice. To evaluate any possible toxic effect of the plant, acute oral toxicity test was performed while the anti-diabetic effects of aqueous and ethanol extracts at 500 mg/kg, positive, negative and normal control were assessed simultaneously. The anti-diabetic study revealed that aqueous extract has higher anti-diabetic potential than ethanol extract while lowered blood glucose level at second week reaching 150 mg/dL, exerting stronger anti-diabetic effects, compared to ethanol extract (190 mg/dL). Oral glucose tolerance findings revealed that aqueous extract decreased blood glucose level by -0.41-fold, compared to ethanol extract showing a decrease by only -0.29-folds. The histopathological evaluation of liver and pancreas of all groups revealed normal cell architecture with no morphological abnormalities. These results suggested the possible use of D. stewartii as anti-diabetic herbal drug in near future. However, these recommendations are conditioned by deep mechanistic studies.

Curcumin inhibits alloxan-induced pancreatic islet cell damage via antioxidation and antiapoptosis.

The present study elucidates the possible protective effects of curcumin on ß-cells damaged by oxidative stress and its significance in controlling diabetes mellitus in in vitro experiments. Pancreatic islet (RIN-m5F) cells were treated with 25 mmol/L alloxan (AXN) to induce cell damage and the protective effects of curcumin were observed. The results showed that curcumin significantly promoted the cellular activity of AXN-treated RIN-m5F cells, decreased the ratio of apoptosis, downregulated the level of malondialdehyde, upregulated the levels of superoxide dismutase and reactive oxygen species, increased the expression of Bcl-2, cleaved caspase-3, and cleaved PARP1, and decreased the expression of Bax in AXN-treated cells. These results suggest that curcumin inhibits AXN-induced damage in RIN-m5F cells via antioxidative and antiapoptotic mechanisms.

Protective effects of Cynara scolymus leaves extract on metabolic disorders and oxidative stress in alloxan-diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. METHODS: We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. RESULTS: The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. CONCLUSION: These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.

Antinociceptive and Antihyperalgesic Activity of a Traditional Maya Herbal Preparation Composed of Pouteria Campechiana, Chrysophyllum Cainito, Citrus Limonum, and Annona Muricata.

Preclinical Research The purpose of this work was to assess the antinociceptive and antihyperalgesic properties of an herbal preparation, composed of four vegetal species: Pouteria campechiana (P. campechiana), Chrysophyllum cainito (C. cainito), Citrus limonum (C. limonum), and Annona muricata (A. muricata), that is commonly used in combination (PCCA) in traditional Mayan medicine for the treatment of diabetes and pain. An ethanolic extract of PCCA was prepared at a ratio of 1:1:1:1 for each plant. The systemic antinociceptive effect of PCCA extract (50-600 mg/kg, p.o.) was dose-dependent in the rat formalin (1%) producing 66% antinociceptive response at 400 mg/kg, p.o. A concentration-dependent antinociceptive effect of the PCCA extract (20-160 mg/paw) was also demonstrated in the rat capsaicin (0.2%) test. The PCCA extract (100-400 mg/kg, p.o.) had antihyperalgesic effects in alloxan diabetic rats. These findings demonstrate the antinociceptive and antihyperalgesic effects of PCCA and supports the use of the plant extracts in Mayan folk medicine. Drug Dev Res 78 : 91-97, 2017. © 2017 Wiley Periodicals, Inc.

A Protein Isolate from Moringa oleifera Leaves Has Hypoglycemic and Antioxidant Effects in Alloxan-Induced Diabetic Mice.

Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo-LPI, and the hypoglycemic and antioxidant effects on alloxan-induced diabetic mice were assessed. Mo-LPI was obtained by aqueous extraction, ammonium sulphate precipitation and dialysis. The electrophoresis profile and proteolytic hydrolysis confirmed its protein nature. Mo-LPI showed hemagglutinating activity, cross-reaction with anti-insulin antibodies and precipitation after zinc addition. Single-dose intraperitoneal (i.p.) administration of Mo-LPI (500 mg/kg·bw) reduced the blood glucose level (reductions of 34.3%, 60.9% and 66.4% after 1, 3 and 5 h, respectively). The effect of Mo-LPI was also evidenced in the repeated dose test with a 56.2% reduction in the blood glucose level on the 7th day after i.p. administration. Mo-LPI did not stimulate insulin secretion in diabetic mice. Mo-LPI was also effective in reducing the oxidative stress in diabetic mice by a decrease in malondialdehyde level and increase in catalase activity. Mo-LPI (2500 mg/kg·bw) did not cause acute toxicity to mice. Mo-LPI is a promising alternative or complementary agent to treat diabetes.

Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat.

BACKGROUND: This study was designed to investigate the effects of immature carob pod aqueous extract (ICPAE) on intestinal glucose absorption in vitro and in vivo using an oral glucose tolerance test (OGTT) as well as the potential antidiabetic effect in alloxan-induced diabetic rats. OGTT was carried by administration of glucose (2 g kg-1 , p.o.) and after treatment with extract (50, 100 and 200 mg kg-1 body weight). Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg-1 ). However, the extracts at various doses or glibenclamide (GLB, 10 mg kg-1 body weight) were given by oral administration for 2 weeks. RESULTS: ICPAE (50-2000 µg mL-1 ) exerted dose-dependent reduction of sodium-dependent glucose transport across isolated mice jejunum and the maximal inhibition exceeded 50%.The ICPAE treatment improved glucose tolerance. More importantly, ICPAE at various doses showed a significant reduction in blood glucose and biochemical profiles in diabetic rats. CONCLUSION: Our findings confirm that the degree of maturity of carob characterized by a different phytochemical composition may be responsible for these actions. Therefore, these compounds may be used as a food supplement in hyperglycemia and diabetes treatments. © 2016 Society of Chemical Industry.

Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats.

Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes.

One-third of diabetes mellitus patients develop diabetic nephropathy, and with underlying mechanisms unknown it is imperative that diabetic animal models resemble human disease. The present study investigated the susceptibility to develop diabetic nephropathy in four commonly used and commercially available mouse strains with type 1 diabetes to determine the suitability of each strain. Type 1 diabetes was induced in C57Bl/6, NMRI, BALB/c, and 129Sv mice by alloxan, and conscious glomerular filtration rate, proteinuria, and oxidative stress levels were measured in control and diabetic animals at baseline and after 5 and 10 wk. Histological alterations were analyzed using periodic acid-Schiff staining. Diabetic C57Bl/6 displayed increased glomerular filtration rate, i.e., hyperfiltration, whereas all other parameters remained unchanged. Diabetic NMRI developed the most pronounced hyperfiltration as well as increased oxidative stress and proteinuria but without glomerular damage. Diabetic BALB/c did not develop hyperfiltration but presented with pronounced proteinuria, increased oxidative stress, and glomerular damage. Diabetic 129Sv displayed proteinuria and increased oxidative stress without glomerular hyperfiltration or damage. However, all strains displayed intrastrain correlation between oxidative stress and proteinuria. In conclusion, diabetic C57Bl/6 and NMRI both developed glomerular hyperfiltration but neither presented with histological damage, although NMRI developed low-degree proteinuria. Thus these strains may be suitable when investigating the mechanism causing hyperfiltration. Neither BALB/c nor 129Sv developed hyperfiltration although both developed pronounced proteinuria. However, only BALB/c developed detectable histological damage. Thus BALB/c may be suitable when studying the roles of proteinuria and histological alterations for the progression of diabetic nephropathy.

Hypoglycaemic activity of biosynthesized copper oxide nanoparticles in alloxan-induced diabetic Wister rats.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder that affects the body's ability to produce or use insulin. This study evaluated the hypoglycaemic activity of biosynthesized copper oxide nanoparticles (CuO-NPs) in alloxan-induced diabetic Wister rats. METHODS: CuO-NPs were synthesized via the green route and characterized using different analytical tools. Diabetes was induced intraperitoneally using 90 mg/kg body weight of alloxan monohydrate in albino rats. Thirty (30) rats were randomly divided into 5 groups of 6 rats each and orally treated for 21 days. Groups I and II were treated with 300 mg/kg bwt Cereus hildmannianus extract and CuO-NPs, respectively. Groups III and IV received 5 mg/kg bwt of Glibenclamide and 2 mL of normal saline, respectively, while Group V was left untreated as the diabetic control. Blood glucose (BG) levels and body weight changes were monitored at 3- and 7-day intervals, respectively, throughout 21-day treatment period. Lipid profiles, enzyme assays and histopathological studies of the liver were also carried out. RESULTS: Spheroidal tenorite phase of CuO-NPs with a crystallite size of 62.57 nm, surface area (20.64 m2 /g) and a UV-maximum absorption at 214.27 nm was formed. The diabetic rats treated with 300 mg/kg bwt CuO-NPs had the highest BG lowering ability (from 482.75 ± 27.70 to 124.50 ± 2.50 mg/dL). A significant difference (p < 0.05) in weight gain and serum enzymes was also observed in the CuO-NPs treated group compared with other groups. The CuO-NPs-treated group had a significant increase (p < 0.05) in HDL-cholesterol and a decrease in total cholesterol, triglycerides, LDL-cholesterol and VLDL-cholesterol compared with other groups. CONCLUSION: The green synthesized CuO-NPs nanoparticles significantly reduced (p < 0.05) blood glucose levels in rats and other associated indices and could serve as drug lead in the treatment of diabetes.

Histologic and Biochemical Effect of Balanite aegyptiaca Fruit Extract on Alloxan-Induced Diabetes in Wistar Rats.

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.

The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes.

This study was conducted to evaluate the anti-diabetic and antioxidant effects of hydroalcoholic pomegranate peel extract (APE) in alloxan-induced diabetes rat models. We divided 60 rats into the following six equal groups (n = 10): Healthy control; diabetic control (100 mg/kg alloxan); sham + glibenclamide (10 mg/kg); diabetic + glibenclamide (10 mg/kg); sham + APE (200 mg/kg) and diabetic + APE (200 mg/kg). After 8 weeks, kidneys were taken out for biochemical and molecular studies. Following APE treatment, biochemical parameters including malondialdehyde (MDA), and glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) significantly induced in the treated group as compared with the control group (p < 0.05). Also, gene expression of GPx (3-fold), CAT (2.6-fold), and SOD (1.5-fold) were increased as compared to controls (p < 0.05). Overall, our results indicated that pomegranate can be used as an antioxidant agent to reduce complications from diseases associated with oxidative stress.

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.

Antioxidant properties of date seeds extract (Phoenix dactylifera L.) in alloxan induced damage in rats.

The study was conducted to examine the antioxidant activity and evaluate the protective effects of the date seeds powder kentichi against alloxan-induced damage in the liver, kidney, and pancreas in diabetic's rats. Group 1: control group, that did not receive any treatment, Group 2: alloxan was injected intraperitoneally (120 mg/kg body weight) for two days (Diab), Group 3: treated only by date seeds powder added in the diet (300 g/kg) for 6 weeks (DSPK), Group 4: alloxan-diabetic rats treated with date seeds powder (300 g/kg) (DSPK + Diab). Estimations of biochemical parameters in blood were determined. TBARS, SOD, CAT, and GPx activities were determined. A histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin hematoxylin-eosin staining. In addition, the antioxidant activities of DSPK were evaluated by DPPH radical scavenging activity, reducing power, and ABTS free radical scavenging. The results revealed that date seeds significantly decreased serum levels of glucose, cholesterol, triglycerides, urea, creatinine, T-protein, ALP, D-bili and T-bili levels. In addition, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities that had been reduced in liver, kidney, and pancreas of the treated group were restored by DSPK treatments and, therefore, the lipid peroxidation level was reduced in the liver, kidney and pancreas tissue compared to the control group. Additionally, the histological structure in these organs was restored after treatment with date seeds powder.

Effect of Croatian propolis on diabetic nephropathy and liver toxicity in mice.

BACKGROUND: In the present study, we examined the antioxidant effect of water soluble derivative of propolis (WSDP) and ethanolic (EEP) extract of propolis on renal and liver function in alloxan-induced diabetic mice. In addition, we examined whether different extract of propolis could prevent diabetic nephropathy and liver toxicity by inhibiting lipid peroxidation in vivo. METHODS: Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75 mg kg-1). Two days after alloxan injection, propolis preparations (50 mg kg-1 per day) were given intraperitoneally for 7 days in diabetic mice. Survival analysis and body weights as well as hematological and biochemical parameters were measured. The renal and liver oxidative stress marker malonaldehyde levels and histopathological changes were monitored in the liver and kidney of treated and control mice. RESULTS: Administration of propolis to diabetic mice resulted in a significant increase of body weight, haematological and immunological parameters of blood as well as 100% survival of diabetic mice. Alloxan-injected mice showed a marked increase in oxidative stress in liver and kidney homogenate, as determined by lipid peroxidation. Histopathological observation of the liver sections of alloxan-induced diabetic mice showed several lesions including cellular vacuolization, cytoplasmic eosinophilia and lymphocyte infiltrations, but with individual variability.Treatment of diabetic mice with propolis extracts results in decreased number of vacuolized cells and degree of vacuolization; propolis treatment improve the impairment of fatty acid metabolism in diabetes. Renal histology showed corpuscular, tubular and interstitial changes in alloxan-induced diabetic mice. Test components did not improve renal histopathology in diabetic mice. CONCLUSIONS: Propolis preparations are able to attenuate diabetic hepatorenal damage, probably through its anti-oxidative action and its detoxification proccess as well as the potential to minimize the deleterious effects of free radicals on tissue. The protective role of propolis against the ROS induced damages in diabetic mice gives a hope that they may have similar protective action in humans.

Improvement of the bioavailability and glycaemic metabolism of cinnamon oil in rats by liquid loadable tablets.

The purpose of this study is to investigate the bioavailability and glycaemic metabolism of cinnamon oil (CIO) carried by liquid-loadable tablets (CIO-LLTs), the carrier of a CIO self-emulsifying formulation (CIO-LS). The results of tests performed to evaluate the physical properties of the CIO-LLT complied with Chinese Pharmacopeia (2010). The release profile suggested that the CIO-LLT preserved the enhancement of in vitro dissolution of cio. After orally administration, the plasma concentration-time profile and pharmacokinetic parameters suggested that a significant increase (P < 0.0001) in the C(max), AUC and F were observed in the CIO-LLT. The blood glucose and the HbA1c were significantly decreased in alloxan-induced hyperglycemic rats (P < 0.05, P < 0.01, resp.), while the level of insulin secretion was markedly elevated in alloxan-induced hyperglycemic rats (P < 0.05). The alloxan-damaged pancreatic ß-cells of the rats were partly recovered gradually after the rats were administered with CIO-LLT 45 days later. CIO-LLT could improve the bioavailability and glycaemic metabolism of CIO.

Model of Streptozotocin-nicotinamide Induced Type 2 Diabetes: a Comparative Review.

The aim of the present study was to review the streptozotocin-nicotinamide (STZ-NA) diabetes model. Type 2 diabetes is more prevalent (90-95%) in adults than type 1. Experimentally- induced diabetes models may be established by chemicals, viral agents, insulin antibodies, surgery, etc. The most advisable and prompt method to induce diabetes is using chemicals, and STZ and alloxan are widely used chemicals. STZ has proven to be a better diabetogenic agent than alloxan because alloxan has many drawbacks, as it induces only type 1 diabetes, has a high mortality rate in rats, and causes ketosis in animals. Moreover, it has lesser selectivity towards ß-cells, and the diabetes-induced is reversible. STZ can be used to induce both type 1 and type 2 diabetes. It is noted that the genotoxic behavior of STZ in animals is accomplished through a reduction of nicotinamide adenine dinucleotide (NAD+) in pancreatic ß-cells via the GLUT2 (Glucose transporter 2), which can cause cellular damage by DNA (Deoxyribonucleic acid) strand breaks that lead to cell death. NA is a biochemical precursor of NAD+, and it is a poly-ADP-ribose-polymerase-1 (PARP- 1) inhibitor. NAD+ is an important redox reaction co-enzyme for the production of adenosine triphosphate (ATP) and many other metabolic pathways. Extreme DNA damage contributes to the over-activation of PARP-1, loss of cellular resources, and necrotic cells death. Some studies have expressed that NA can protect pancreatic ß-cells against the severe cytotoxicity of STZ. The review concluded that the STZ-NA model is dependent on the competency of NA to attain partial protection against the ß-cytotoxic essence of STZ to induce type-2 diabetes.