Alloxan-induced Diabetic Model Research Articles

Development and Biological Evaluation of Gymnema Sylvestre Extract-Loaded Nonionic Surfactant-Based Niosomes

To develop and characterize Gymnema sylvestre extract-loaded niosomes using nonionic surfactants, and to evaluate their antihyperglycemic efficacy in comparison with the parent extract. Nonionic surfactant-based G. sylvestre extract-loaded niosomes were prepared using the thin-film hydration method. The optimized formulation was screened for entrapment efficiency of the constituents, as well as other parameters such as release kinetics, vesicle size, zeta-potential and stability studies. The parent extract and optimized niosomal formulation were evaluated for their antihyperglycemic potential in an alloxan-induced diabetic animal model. Niosomes prepared using Span™ 40 (SD Fine Chemicals Ltd, Mumbai, India) provided sterically stable vesicles 229.5 nm in size with zeta-potential and entrapment efficiency of 150.86 mV and 85.3 ± 4.5%, respectively. The surface morphology of vesicles was confirmed to be spherical by scanning electron microscopy studies. An in vitro release study demonstrated 77.4% of phytoconstituents release within 24 h. The niosome formulation demonstrated significant blood glucose level reduction in an oral glucose tolerance test, and increased antihyperglycemic activity compared with the parent extract in an alloxan-induced diabetic model. This study reveals the merits of G. sylvestre extract-loaded niosomes, and justifies the potential of niosomes for improving the efficacy of G. sylvestre extract as antidiabetic. Original submitted 30 March 2012; Revised submitted 29 August 2012; Published online 24 December 2012.

MODULATING EFFECT OF CAMEL’S MILK ON ALLOXAN-INDUCED EXPERIMENTAL DIABETES IN LABORATORY ANIMAL MODEL

The present study was conducted to evaluate the hypoglycemic effect of camel's milk in alloxan-induced diabetic animal model compared to control and cow's milk receiving groups. This study was carried out on thirty five female white albino rats and divided into 2 main groups: optimizing and experimental group. Optimizing group (n = 20) was used to determine the optimal dose of alloxan to induce diabetes in a pattern of dose response relationship. This group was divided into four subgroups, sG1 to sG4, (n = 5 each). sG1, sG2, sG3, and sG4 were injected intra- peritoneally with alloxan monohydrate at a dose 100, 140, 180 and 200 mg/kg B.W., respectively. Experimental group (n =15) was divided into three subgroups (n = 5 each) as following: diabetic rats receiving no treatment and acts as a positive control (sG1), diabetic rats receiving camel's milk (sG2) and diabetic rats receiving cow's milk (sG3). Their blood glucose levels (BGLs) were estimated at weekly interval for 5 consecutive weeks. A baseline BGL was determined before conducting the experiment and it was 79.85 ± 4.2 mg/dl. The results showed that 140 mg/kg B.W. of alloxan was the optimal dose to induce stable diabetes in the optimizing group. In the experimental group, the initial mean BGLs for sG1, sG2, and sG3 were 399.5 ± 18.3, 429.4 ± 66.4 and 404.6 ± 53.6 mg/dl, respectively and after 5 th week there were 488.2 ± 20.8, 308.28 ± 52.2, 519.8 ± 131.5 mg/dl respectively. Most diabetic animals that received cow's milk exhibits severe signs of diabetes at 4 th week of experiment and died by 5 th week while animals that received camel's milk showed marked improvement and one of them exhibited normal BGL by the end of experiment. Our findings suggested that administration of camel's milk was effective in improvement of the alloxan-induced diabetic rats and recommended as nutraceuticals supplement in diabetic patient.

Topical Administration of Allogeneic Mesenchymal Stromal Cells Seeded in a Collagen Scaffold Augments Wound Healing and Increases Angiogenesis in the Diabetic Rabbit Ulcer

There is a critical clinical need to develop therapies for nonhealing diabetic foot ulcers. Topically applied mesenchymal stromal cells (MSCs) provide a novel treatment to augment diabetic wound healing. A central pathological factor in nonhealing diabetic ulcers is an impaired blood supply. It was hypothesized that topically applied allogeneic MSCs would improve wound healing by augmenting angiogenesis. Allogeneic nondiabetic bone-marrow derived MSCs were seeded in a collagen scaffold. The cells were applied to a full-thickness cutaneous wound in the alloxan-induced diabetic rabbit ear ulcer model in a dose escalation fashion. Percentage wound closure and angiogenesis at 1 week was assessed using wound tracings and stereology, respectively. The topical application of 1,000,000 MSCs on a collagen scaffold demonstrated increased percentage wound closure when compared with lower doses. The collagen and collagen seeded with MSCs treatments result in increased angiogenesis when compared with untreated wounds. An improvement in wound healing as assessed by percentage wound closure was observed only at the highest cell dose. This cell-based therapy provides a novel therapeutic strategy for increasing wound closure and augmenting angiogenesis, which is a central pathophysiological deficit in the nonhealing diabetic foot ulcer.

Hypoglycemic and Antidiabetic Profile of the Aqueous Root Extracts of Leptadenia hastata in Albino Rats

This study was designed to evaluate the antidiabetic profile and the hypoglycaemic activity of aqueous root extracts of L. hastata in normal and alloxan-induced diabetic rats model. Eighty five albino rats were used for this study out of this thirty five were used subjected to experimental diabetes by the use of alloxan at a dose of 160 mg kg(-1) body weight. Seven experimental groups of five rats per group (A-G) were used for this study. A standard antidiabetic drug (insulin) group (B) and normal saline group (G) serves as positive control. The blood glucose lowering activity of the extract, insulin and normal saline groups were monitored at 0, 1, 3, 6, 12 and 18 hpost extract administration. On the other hand the remaining fifty albino rats were used to determine the acute toxicity and the hypoglycemic activity of the extract. The blood glucose levels of the rats were monitored at 0, 7, 14, 21 and 28 days post extract administration. Oral administration of aqueous root extract at 600 and 800 mg kg(-1) b.wt have significantly (p < 0.05) decreased the blood glucose in diabetic albino rats. On the other hand the hypoglycemic activity of the aqueous root extract on normal rats at dose of 1000 mg kg(-1) b.wt have significantly (p < 0.05) decreases blood glucose level in normal albino rats. The results of the current study have demonstrated the antidiabetic and hypoglycaemic effects of L. hastata aqueous root extracts and underscore its potentials in the management of diabetes mellitus especially following prolonged use in days.

Evaluation of in vivo anti-hyperglycemic and antioxidant potentials of α-santalol and sandalwood oil

Sandalwood finds numerous mentions across diverse traditional medicinal systems in use worldwide. The objective of this study was to evaluate the in vivo anti-hyperglycemic and antioxidant potential of sandalwood oil and its major constituent α-santalol. The in vivo anti-hyperglycemic experiment was conducted in alloxan-induced diabetic male Swiss albino mice models. The in vivo antioxidant experiment was performed in d-galactose mediated oxidative stress induced male Swiss albino mice models. Intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for an week modulated parameters such as body weight, blood glucose, serum bilirubin, liver glycogen, and lipid peroxides contents to normoglycemic levels in the alloxan-induced diabetic mice. Similarly, intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d-galactose mediated oxidative stress induced mice. Besides, it was observed that the beneficial effects of α-santalol were well complimented, differentially by other constituents present in sandalwood oil, thus indicating synergism in biological activity of this traditionally used bioresource.

The Medicinal Cracked-Cap Polypore Mushroom Phellinus rimosus (Higher Basidiomycetes) Attenuates Alloxan-Induced Hyperglycemia and Oxidative Stress in Rats

Diabetes is usually associated with increased production of reactive oxygen species (ROS), impaired antioxidant defense systems, or both, which result in oxidative damage and lead to ROS-mediated diabetic pathogenesis. This investigation was undertaken to evaluate the role of extract from the wood-inhabiting polypore medicinal mushroom Phellinus rimosus in an alloxan-induced diabetic model and the oral glucose tolerance test in rats. Oral administration of extract at doses of 50 and 250 mg/kg body weight/day for 10 days to rats with alloxan-induced diabetes was found to possess significant dose-dependent hypoglycemic activity. In the oral glucose tolerance test, hypoglycemic effect of P. rimosus (250 mg/kg) was significant (P < 0.01) and maximum at 90 minutes after the glucose challenge when compared with that of control group. The effect of extract on antioxidant status in the pancreas, liver, and kidney was estimated. The diabetic control rats exhibited elevated levels of lipid peroxidation and lower activities of copper/zinc superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) content in pancreatic, hepatic, and renal tissues compared with normal tissues. The activities of SOD, CAT, GPx, and GSH were found to be increased in diabetic rats treated with the extract. The increased level of lipid peroxidation in diabetic rats also was found to revert to near-normal status in groups treated with the extract. The findings thus suggest the therapeutic efficiency of Ph. Rimosus against declined antioxidant status as well as hyperglycemia associated with diabetes.

Biochemical evaluation of the hypoglycemic effects of extract and fraction of Cassia fistula linn. in alloxan-induced diabetic rats

Various extracts of flowers of Cassia fistula Linn (Leguminosae) such as petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous, and crude aqueous extracts and two fractions of ethanol extract were tested for antihyperglycemic activity in glucose-overloaded hyperglycemic rats. The effective antihyperglycemic extracts and fraction were tested for their hypoglycemic activity at two dose levels, 200 and 400 mg/kg, respectively. To confirm their utility in higher models, the effective extracts and fraction of C. fistula were subjected to antidiabetic study in an alloxan-induced diabetic model at two dose levels, 200 and 400 mg/kg, respectively. Biochemical parameters like glucose, urea, creatinine, serum cholesterol, serum triglyceride, high-density lipoprotein, low-density lipoprotein, hemoglobin, and glycosylated hemoglobin were also assessed in experimental animals. The petroleum ether and ethanol extracts of C. fistula and the water-soluble fraction of ethanol extract were found to exhibit significant antihyperglycemic activity. The extracts, at the given doses, did not produce hypoglycemia in fasted normal rats, and the fraction exhibited weak hypoglycemic effect after 2 h of the treatment. Treatment of diabetic rats with ethanol extract and water-soluble fraction of this plant restored the elevated biochemical parameters significantly (P<0.05) to the normal level. No activity was found in the petroleum ether extract of the plant. Comparatively, the water-soluble fraction of ethanol extract was found to be more effective than the ethanol extract, and the activity was comparable with that of the standard, glibenclamide (5 mg/kg).

Effect of Piperine on Antihyperglycemic Activity and Pharmacokinetic Profile of Nateglinide

Piperine (CAS no: 94-62-2), an alkaloid obtained from Piper nigrum and P. longum is a known inhibitor of various enzymes (CYP isozymes) responsible for biotransformation of drugs. By inhibiting the metabolism of drugs, piperine improves the bioavailability of drugs. In the present study piperine (10 mg/kg) significantly increased the dose-dependent anti-hyperglycemic activity of nateglinide (CAS no: 105816-04-4) as evaluated by glucose challenged and alloxan-induced diabetic models, when it was administered with nateglinide. Nateglinide plasma concentrations were also increased, when administered with piperine. The synergistic anti-hyperglycemic activity of nateglinide when administered with piperine can be attributed to increased plasma concentration of nateglinide. The results of this study demonstrate that piperine could be used as a potential bioenhancer along with nateglinide.

751. Autologous Circulating Angiogenic Cells Treated with Osteopontin and Delivered Via a Collagen Scaffold Enhances Wound Healing in the Alloxan-Induced Diabetic Rabbit Ear Ulcer Model

751. Autologous Circulating Angiogenic Cells Treated with Osteopontin and Delivered Via a Collagen Scaffold Enhances Wound Healing in the Alloxan-Induced Diabetic Rabbit Ear Ulcer Model

Isolation of Antidiabetic Principle from Fruit Rinds ofPunica granatum

Present study was aimed to isolate and evaluate the antidiabetic activity of phytoconstituents from fruit rinds of Punica granatum. With the above objectives Valoneic acid dilactone (VAD) was isolated from methanolic fruit rind extracts of Punica granatum (MEPG) and confirmed by 1H-NMR, 13C-NMR, and mass spectral data. Antidiabetic activity was evaluated by Aldose reductase, α-amylase and PTP1B inhibition assays in in vitro and Alloxan-induced diabetes in rats was used as an in vivo model. In bioactivity studies, MEPG and VAD have showed potent antidiabetic activity in α-amylase, aldose reductase, and PTP1B inhibition assays with IC50 values of 1.02, 2.050, 26.25 μg/mL and 0.284, 0.788, 12.41 μg/mL, respectively. Furthermore, in alloxan-induced diabetes model MEPG (200 and 400 mg/kg, p.o.) and VAD (10, 25, and 50 mg/kg, p.o.) have showed significant and dose dependent antidiabetic activity by maintaining the blood glucose levels within the normal limits. Inline with the biochemical findings histopathology of MEPG (200 and 400 mg/kg, p.o.), VAD (10, 25, and 50 mg/kg, p.o.), and glibenclamide (10 mg/kg, p.o.) treated animals showed significant protection against alloxan-induced pancreatic tissue damage. These findings suggest that MEPG and VAD possess significant antidiabetic activity in both in vitro and in vivo models.

Palladium-α-lipoic acid complex attenuates alloxan-induced hyperglycemia and enhances the declined blood antioxidant status in diabetic rats

Palladium α-lipoic acid (Pd-LA) complex has unique electronic and redox properties that appear to be the key to its physiological effectiveness. A proprietary liquid blend containing Pd-LA as the major component was demonstrated to be effective in improving the activities of mitochondrial enzymes in aged rats. The Pd-LA complex was evaluated for its hypoglycemic effect against the alloxan-induced diabetic model, as well as in the oral glucose tolerance test in rats. The in vitro free radical scavenging activity of Pd-LA was also determined. Administration of Pd-LA (0.5 mL/kg; equivalent to 3.8 mg complexed α-lipoic acid/kg, p.o.) daily for 5 days to alloxan-induced diabetic animals significantly reduced the blood glucose level (P < 0.05). The blood antioxidant status in the diabetic animals was significantly improved by the treatment of Pd-LA (P < 0.05). Similarly, Pd-LA showed significant in vitro antioxidant activity in a concentration-dependent manner. Results of the study conclude that the Pd-LA complex is effective in lowering the blood glucose level and enhancing the declined antioxidant status in diabetic animals. Significant finding(s) of the study include: (i) Pd-LA significantly increased the tolerance of glucose and was also effective in ameliorating hyperglycemia induced by alloxan; (ii) Pd-LA significantly enhanced the activities of blood superoxide dismutase, catalase, glutathione peroxidase and level of glutathione in diabetic animals; and (iii) Pd-LA showed significant in vitro antioxidant activity. This study adds: The therapeutic efficiency of Pd-LA is demonstrated against declined antioxidant status as well as hyperglycemia associated with diabetes.

The Influence of Alloxan-Induced Diabetes on Müller Cell Contraction-Promoting Activities in Vitreous

Previous studies from this laboratory revealed that vitreous insulin-like growth factor biological activity increases in diabetes and that this change can precede the onset of proliferative diabetic retinopathy. The goal of this study was to characterize this phenomenon in an animal model of alloxan-induced diabetes. Swine made diabetic with intravenous alloxan were euthanized at times varying from 0 to 90 days. Vitreous samples from normal and diabetic swine were evaluated for changes in Müller cell contraction-promoting activity, the presence of insulin-like growth factor binding protein (IGFBP), and carbonic anhydrase-I and -II. Ocular tissues from these animals were also evaluated for changes in contraction-promoting growth factors and IGFBP message levels. Alloxan-induced diabetes is associated with significant increases in vitreous Müller cell contraction-promoting activity that are present in as few as 30 days and are sustained for at least 90 days. Biochemical studies revealed that the increases cannot be attributed to loss of growth factor-attenuating IGFBPs, changes in local expression of contraction-promoting growth factors, or vitreous hemorrhage. The previously reported increases in Müller cell contraction-promoting activity detected in human diabetic vitreous are present in diabetic swine within 30 days of chemical induction. The increase does not appear to be attributable to loss of growth factor control, increases in local growth factor expression, or vitreous hemorrhage, suggesting that other mechanisms are involved. It is the authors' speculation that diabetes induces blood-vitreous barrier changes that allow a different subset of plasma proteins to enter vitreous fluids.

Antidiabetic activity of &lt;i&gt;anacardium occidentale&lt;/i&gt; in alloxan – diabetic rats

This study investigated the hypoglycemic effect of inner bark extract of Anacardium occidentale Linn. (Anacardiceae) in normal (normoglycemic) and in alloxan-induced diabetic rats. The inner reddish bark of the plant was extracted with ethanol and screened for hypoglycemic activity in a model of alloxan-induced diabetes in at species. Bioactivity-guided fractionation of the ethanolic extract led to fractions that displayed diverse hypoglycemic effects at doses of 34.0, 200.0 and 300.0 mg/kg body weight. The alloxan-diabetic rats showed significant reduction in plasma glucose level after treatment with the fractions. These results lend support to the validity of the folkloric use of A. occidentale in the treatment of diabetes mellitus type II.

Anomalies in alloxan-induced diabetic model: It is better to standardize it first.

Sir, Antidiabetic effect of more than 500 plants has been proved in alloxan-induced diabetic animal models but further medical research does not support their effectiveness. We also have been not able to get a single effective antidiabetic molecule from them. It is also understood that alloxan-induced diabetic model does not exactly simulate the human type 2 diabetes mellitus. Some herbomineral products, which have antidiabetic effect in animal models, were not effective in humans as an antidiabetic. Shilajeet and Gymmema sylvestre have antidiabetic effects in alloxan-induced animal model but these herbs have no antidiabetic effects when studied in man. There are inconsistencies in doses of drugs, routes of administration, duration and severity of diabetes and methodology in alloxan-induced diabetic models, which make its accuracy controversial. The pharmacokinetic and pharmacodynamic profile of alloxan is ignored by researchers working on these aspects. We wish to make the following observations in this regard. Alloxan is very rapidly destroyed in the body. Its half-life is less than 1 minute. Hence, its action is most unpredictable unless it is administered by rapid intravenous injection. Slow rate of intravenous injection reduces the efficacy of the agent.[1] But in alloxan-induced models, researchers usually use intraperitoneal or other routes, which makes it less capable to induce diabetes of such duration as required for study. During intraperitoneal, intramuscular and subcutaneous routes of administration, onset of alloxan action would be delayed. Will it not be sufficient to destroy alloxan in body? Will delayed onset of action not make it less efficient in producing diabetes in animals? Very young animals have a high resistance to the diabetogenic effect of alloxan.[2] Damage to the renal tubules by alloxan also alters blood glucose level which may also influence the results of study. The susceptibility to both toxic and diabetogenic doses varies widely not only in different species but also among animals of the same species.[1] Rats were more sensitive to a constant dose of alloxan after a fore period on a high fat diet and less sensitive after a high carbohydrate and protein diet.[3] The spontaneous recovery is particularly evident in rats and mice, in which the majority of animals become normoglycemic. The recovery from the diabetes is believed to be the consequence of either a multiplication of β cells from the duct epithelium or the exocrine portion of the pancreas.[4] This is the reason why mild diabetes produced by alloxan recovers spontaneously in rats. Lower doses of alloxan (90-140 mg/kg, i.p.) can result in auto-reversion to normal state. It has been found that in many research studies, the dose of alloxan used to induce diabetes was suboptimal. In these studies, it was found that alloxan induces very mild diabetes. However, in these animals, revert back to the blood glucose values reverted back to normal in a week. β cells of islet of Langerhans in rats show regenerative capacity.[5] Thus, the illusion of antidiabetic effect of experimental product is produced. Production of diabetes also depends upon the speed of the intravenous injections at a given dose level, the slower injection rates causing less effect.[6] Human islet tissue is exceedingly resistant to the degenerative effects of alloxan. Alloxan diabetes differs strikingly from other types of experimental diabetes in the course and nature of the lesions which are developed. As yet, there is no evidence that alloxan-induced diabetes mellitus is related to human diabetes mellitus.[7] Hence, there are many inconsistencies and anomalies in alloxan-induced diabetic models. By analyzing the above observations and studies mentioned by many authors, it indicates that alloxan-induced diabetic model is a doubtful model for antidiabetic studies. Hence, further studies are needed to evaluate ideal antidiabetic model. Only then, we can develop new effective antidiabetic molecules.

P2-13 VEGF expression in an alloxan-induced diabetic rabbit model

P2-13 VEGF expression in an alloxan-induced diabetic rabbit model

N-acetyl cysteine promotes angiogenesis and clearance of free oxygen radicals, thus improving wound healing in an alloxan-induced diabetic mouse model of incisional wound

This study investigated whether N-acetyl cysteine induces any favourable effects on cutaneous incisional wound healing in diabetic and nondiabetic mice. The wounds were assessed using detection of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) expression, and wound-breaking strength (WBS) measurements. In total, 48 BALB/c mice were used. These were divided into four groups, each consisting of 12 mice. Incisional wounds were made on the back of each mouse. Two of the groups consisted of healthy animals and the other two groups consisted of mice with alloxan-induced diabetes. One group of healthy mice and one group of diabetic mice received intraperitoneal N-acetyl cysteine (NAC) 150 mg/kg for 5 consecutive days, while the other two groups were untreated. On the fifth day all animals were killed, and the WBS, oxidative stress parameters, histopathological and immunohisotchemical results were assessed. Both diabetic and nondiabetic mice receiving NAC had lower levels of oxidative stress markers and higher WBS measurements than untreated counterparts. A mouse model of incisional wound treated with NAC resulted in lower levels of tissue oxidative stress, higher levels of tissue glutathione, and downregulation of iNOS expression coupled with upregulation of VEGF expression, producing an overall favourable clinical outcome of higher WBS and a shorter wound-healing period both in diabetic and nondiabetic mice. Both antioxidant and anti-inflammatory properties of NAC may be involved in this improved healing process for incisional wounds.

Evaluation of the Antiradical Activity of Schisandra Chinensis Lignans Using Different Experimental Models

The in vitro antiradical activity of Schisandra chinensis lignans was investigated using DPPH, ABTS+, Fenton reaction inhibition and tyrosine-nitration inhibition assays, as were the in vivo antidiabetic activities of selected lignans in an animal model of alloxan-induced diabetes. Different degrees of antiradical activity were found, depending upon the structural parameters of the tested compounds. Unfortunately, the compounds showed no antidiabetic activity in concentration range tested.

Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

BackgroundWhile all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated.MethodsIn alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB) activation induced by IL-1β and IFN-γ was investigated.ResultsIn alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation.ConclusionWe have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

Antidiabetic activity of extracts and fraction of Zizyphus mauritiana

Various extracts, petroleum ether, chloroform, acetone, ethanol, aqueous, and crude aqueous, of fruits of Zizyphus mauritiana Lam. (Rhamnaceae) and the fractions of petroleum ether and aqueous extracts were tested for antihyperglycemic activity in glucose overloaded hyperglycemic rats. The effective antihyperglycemic extracts and fraction were tested for their hypoglycemic activity at two dose levels, 200 and 400 mg/kg, respectively. To confirm their utility in a higher model, the effective extracts and fraction of Z. mauritiana were also subjected to an antidiabetic study in the alloxan-induced diabetic model at two dose levels, 200 and 400 mg/kg. The aqueous extract and the non-polysaccharide fraction of the aqueous extract of Z. mauritiana were found to exhibit significant antihyperglycemic and hypoglycemic activities. The petroleum ether extract was found to exhibit only an antihyperglycemic effect. Treatment of diabetic rats with petroleum ether extract, aqueous extract, and non-polysaccharide fraction of this plant restored the elevated biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, HDL, LDL, hemoglobin, and glycosylated hemoglobin significantly to the near normal level. Comparatively, the non-polysaccharide fraction of the aqueous extract was found to be more effective, followed by the aqueous extract, and the petroleum ether extract. The activity of the non-polysaccharide fraction was comparable to that of the standard drug glibenclamide.

Assessment of Wound Healing in the Alloxan-Induced Diabetic Rabbit Ear Model

The enhancement of diabetic wound healing represents a major clinical challenge to researchers. The challenge faced is to identify a suitable animal model that best represents the human situation. However, the majority of diabetic wound healing models are in rodents and are hindered by rapid contraction and thus do not reflect epithelial cell migration, as seen in the human wound. The alloxan-induced diabetic rabbit model is a cheap, reproducible model and offers the advantage of providing a noncontractile avascular wound bed. This study aimed to compare the effects of acute hyperglycemia in the alloxan model to normal rabbit controls on wound healing, using methods of stereology. Alloxan was administered 7 days prior to surgery. Four full-thickness punch biopsy wounds were created on each ear (n = 4). Wounds were excised at 7 and 14 days and prepared for stereological analysis from Masson's trichrome-stained histological sections. It was noted that the alloxan-treated animals showed an increase in the number of inflammatory cells and fibroblasts at 14 days. In addition, it was noted that the length density of blood vessels was reduced in the alloxan-induced diabetic rabbits, representing a greater radial diffusion distance between vessels and a less efficient network for nutrient exchange. This is the first study to take a stereological approach to defining the effects of diabetes mellitus on wound healing in a noncontractile model.