Mentha piperita silver nanoparticle-loaded hydrocolloid film for enhanced diabetic wound healing in rats.

OBJECTIVE: To investigate the role of Mentha piperita silver nanoparticle-loaded carbopol gel for enhanced wound healing in a diabetic rat model. This research further aims to explore bioactive compounds derived from Mentha piperita obtained from high altitude. METHOD: Methanolic extracts of Mentha piperita (MP), Mentha spicata (MS) and Mentha longifolia (ML) were used to synthesise silver nanoparticles (AgNP). AgNP synthesis was confirmed by ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The antioxidant activity was assessed by 2, 2-diphenyl-1-picrylhydrazyl (DDPH) assay. Antiglycation potential was determined by measuring the fluorescent advanced glycation end products. The bioactive compound identified in the Mentha piperita methanolic (MPM) fraction through electrospray ionisation tandem mass spectrometric analysis (ESI-MS) was responsible for the highest antiglycation. The effects of MPM and MPM.AgNP-loaded Carbopol (Sanare Lab, India) on wound healing were compared in male, alloxan-induced, diabetic albino rats (200-250g), divided into control and treated groups. Effects on wound healing were assessed via histopathology. RESULTS: UV-Vis and FTIR confirmed NP synthesis with peaks for flavonoids and polyphenols. SEM and XRD explored the cubical, 30-63nm crystalline NP. The maximum antioxidant and antiglycation potential was observed in order of; MP.AgNP>MS.AgNP>ML.AgNP. The highest antioxidant activity was observed by methanolic and aqueous MP.AgNPs (88.55% and 83.63%, respectively) at 2mg.ml-1, and (75.16% and 69.73%, respectively) at 1mg.ml-1, compared to ascorbic acid (acting as a positive control, 90.01%). MPM.AgNPs demonstrated the best antiglycation potential of 75.2% and 83.3% at 1mg.ml-1 and 2mg.ml-1, respectively, comparable to positive control (rutin: 88.1%) at 14 days post-incubation. A similar trend was observed for antimicrobial activity against Bacillus subtilis, Micrococcus luteus and Escherichia coli with an inhibition zone of 21mm, 21.6mm and 24.6mm. Rosmarinic acid was the active compound present in Mentha piperita, as identified by ESI-MS. MPM.AgNP-loaded Carbopol resulted in 100% wound closure compared with control at 20 days post-wounding. In the treatment group, re-epithelialisation was achieved by day 18, compared with 25 days for the positive control group. CONCLUSION: MPM.AgNP-loaded Carbopol demonstrated safer and more effective biological properties, hence accelerating the diabetic excision wound healing process in alloxan-induced diabetic rats.

Fructooligosaccharides from Cynoglossum tubiflorus: Effect of the molecular size on their antidiabetic activity in high-fat diet and alloxan induced diabetic rats.

The use of acetylation followed by silica gel column purification allowed the isolation of eight fructooligosaccharides (FOS) from the ethanol extract of Cynoglossum tubiflorus roots. Each FOS was identified by analyzing its FT-IR, HRMS/MS and NMR data, including 1H, 13C and 2D NMR HH COSY, HMBC and NOESY. In diabetic rats treated with a series of FOS from Glc-(Fru)3 to Glc-(Fru)7, a significant inhibition of intestinal α-amylase was observed. This activity increases proportionally with the FOS molecular size. It was found that they delay the absorption of total cholesterol (TC), ldl-cholesterol (LDL-C) and increase HDL-cholesterol (HDL-C) in a molecular size-dependent manner. This inhibitory effect on the activity of the digestive enzyme causes a significant (p < 0.05) reduction in the level of glucose in the blood as an anti-diabetic action. The ethanolic extract (E.E) exerts a significant effect against α-amylase as well as antihyperglycemic and antihyperlipidemic actions, while its acetylation suppresses these effects. Therefore, this study demonstrates for the first time that pure FOS act as an efficient agent in preventing hyperglycemia and hyperlipidemia and that this action evolves in the same manner with their molecular size.

In vitro antioxidant capacity of Corryocactus brevistylus (sanky) and its effect on the pancreas morphology of alloxan-induced diabetic rats. / Capacidad antioxidante in vitro del Corryocactus brevistylus (sanky) y su efecto en la morfología del páncreas de ratas diabéticas inducidas con aloxano.

OBJECTIVE.: To determine the in vitro antioxidant capacity of Corryocactus brevistylus and its effect on glycemia and the pancreas of alloxan-induced diabetic rats. MATERIALS AND METHODS.: The antioxidant capacity of the hydroethanolic extract of sanky (HEES) was evaluated by assessing its ability to reduce 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion (FRAP). We used thirty adult rats, which were induced to diabetes with two doses of alloxan (80mg/kg). Rats were distributed into 5 groups (n=6), all groups received treatment by orogastric route for eight days. Group I received water, group II received metformin 14mg/kg and groups III, IV and V received sanky juice at 1.0; 4.0 and 16 mL/kg, respectively. Glycemia was evaluated by the rapid method (glucometer) (first and eighth day). After treatment, the animals were sacrificed and the pancreas was removed for histopathological study. RESULTS.: The antioxidant capacity of HEES by DPPH showed an IC50 of 0.77 mg/mL; the FRAP method showed a TEAC-FRAP of 22.31µg/mg. Glycemia decreased on the eighth day of treatment, with respect to the first day; a decrease in glycemia was also found in groups III-V, when compared to group I. Histologically, groups I-II presented severe atrophy and moderate necrosis of the islets of Langerhans; groups IV-V presented hypertrophy and mild multifocal necrosis at the islet level. CONCLUSIONS.: The extract of sanky showed antioxidant capacity in vitro and the juice exerts a hypoglycemic and protective effect on the pancreas.

OBJETIVO.: Determinar la capacidad antioxidante in vitro del Corryocactus brevistylus y su efecto sobre la glicemia y páncreas de ratas diabéticas inducidas con aloxano. MATERIALES Y MÉTODOS.: Se evaluó la capacidad antioxidante del extracto hidroetanólico de sanky (EHES) mediante la capacidad de reducir el 2,2-difenil-1-picrilhidracilo (DPPH) y la capacidad de reducir el ion férrico (FRAP). Se utilizaron 30 ratas adultas inducidas a diabetes con dos dosis de aloxano (80mg/kg), formándose cinco grupos (n=6), recibiendo los tratamientos vía orogástrica durante ocho días, el grupo I (agua), II (metformina 14mg/kg), grupos III-IV-V zumo de sanky a 1,0; 4,0 y 16 mL/kg, respectivamente. La glicemia fue evaluada por el método rápido (glucómetro) (primer y octavo día). Terminado el tratamiento los animales fueron sacrificados y se les extrajo el páncreas, para su estudio histopatológico. RESULTADOS.: La capacidad antioxidante del EHES mediante el DPPH, mostró un IC50 de 0,77 mg/mL, y por el método FRAP se observó el TEAC-FRAP de 22,31µg/mg. La glicemia disminuyó en el octavo día de tratamiento, respecto al primer día; también se observó disminución de la glicemia en los grupos III-V, respecto al grupo I. A nivel histológico los grupos I-II presentaron atrofia severa y necrosis moderada de los islotes de Langerhans; los grupos IV-V presentaron hipertrofia y necrosis leve multifocal a nivel del islote. CONCLUSIONES.: El extracto de sanky presenta capacidad antioxidante in vitro y el zumo ejerce un efecto hipoglicemiante y protector en páncreas.

Therapeutic Potential of Dillenia indica L. in Attenuating Hyperglycemia-Induced Oxidative Stress and Apoptosis in Alloxan-Administered Diabetic Mice.

BACKGROUND: Hyperglycemia-induced oxidative stress accelerates the process of apoptosis in tissues. Dilleniaindica (DI) is a medicinal plant, and its fruit contains many therapeutic properties. The therapeutic activity of the Methanolic Fruit Extract (MFE) of DI in attenuating oxidative stress and apoptosis in the liver and kidney tissues of alloxan-induced diabetic mice was analyzed in the present study. METHODS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE was conducted. GLUT4 protein expression analysis and lipid peroxidation assays were conducted to check for MFE effect by administering in diabetic mice. An ultrastructural study was conducted for both the tissues. In apoptotic studies, the TUNEL assay and apoptotic protein expression analysis was conducted. RESULTS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE showed the presence of two crucial antioxidants, ascorbic acid, and naringenin. In GLUT-4 protein expression analysis, MFE suppresses hyperglycemia by upregulating GLUT4 protein expression. Lipid peroxidation assay showed a decrease in malondialdehyde (MDA) upon MFE administration in diabetic mice. An ultrastructural study was conducted, and MFE was found to restore cellular alterations in diabetic tissues. In apoptotic studies, the TUNEL assay shows that MFE treatment showed fewer apoptotic cells than the diabetic group. The study also observed decreased caspase 3 protein expression and increased Bcl-2 protein expression. CONCLUSIONS: Therefore, it is inferred from the study that MFE can exert a protective effect by suppressing hyperglycemia and modulating oxidative stress and apoptosis in alloxan-administered diabetic mice.

Ameliorative Effects of Flavonoids from Platycodon grandiflorus Aerial Parts on Alloxan-Induced Pancreatic Islet Damage in Zebrafish.

Platycodon grandiflorus (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of P. grandiflorus on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root. Eight flavonoids (1-8) were isolated from the aerial part. Structures of two new flavone glycosides, designated dorajiside I (1) and II (2), were elucidated to be luteolin 7-O-α-L-rhamno-pyranosyl (1 → 2)-(6-O-acetyl)-ß-D-glucopyranoside and apigenin 7-O-α-L-rhamnopyranosyl (1 → 2)-(6-O-acetyl)-ß-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds 1, 3, 4 and 6-8 yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound 7 blocked KATP channels in pancreatic ß-cells. Furthermore, compounds 3, 4, 6 and 7 showed significant changes with respect to the mRNA expression of GCK, GCKR, GLIS3 and CDKN2B compared to alloxan-induced zebrafish. In conclusion, the aerial part of P. grandiflorus and its constituents conferred a regenerative effect on injured pancreatic islets.

Potentilla fulgens upregulate GLUT4, AMPK, AKT and insulin in alloxan-induced diabetic mice: an in vivo and in silico study.

OBJECTIVE: This study was designed to investigate whether the glucose lowering effects of Potentilla fulgens acts by modulating GLUT4, AKT2 and AMPK expression in the skeletal muscle and liver tissues. METHODOLOGY: Alloxan-induced diabetic mice treated with Potentilla fulgens was assessed for their blood glucose and insulin level, mRNA and protein expression using distinguished methods. Additionally, GLUT4, AKT2 and AMPK were docked with catechin, epicatechin, kaempferol, metformin, quercetin and ursolic acid reportedly present in Potentilla fulgens. RESULTS: Potentilla fulgens ameliorates hyperglycaemia and insulin sensitivity via activation of AKT2 and AMPK, increases the expression of GLUT4, AKT2, AMPKα1 and AMPKα2 whose levels are reduced under diabetic condition. Molecular docking revealed interacting residues and their binding affinities (-4.56 to -8.95 Kcal/mol). CONCLUSIONS: These findings provide more clarity vis-avis the mechanism of action of the phytoceuticals present in Potentilla fulgens extract which function through their action on GLUT4, PKB and AMPK.

Annona muricata L. peel extract inhibits carbohydrate metabolizing enzymes and reduces pancreatic ß-cells, inflammation, and apoptosis via upregulation of PI3K/AKT genes.

BACKGROUND AND OBJECTIVE: Annona muricata L. peel has been recognized for many ethnobotanical uses, including diabetes management. However, limited detailed scientific information about its mechanism of antidiabetic activity exists. The objective of this study was to evaluate the anti-diabetic properties of an aqueous extract of A. muricata peel (AEAMP) and its mechanism of action on alloxan-induced diabetic rats. METHODS: In vitro antidiabetic assays, such as α-amylase and α-glucosidase were analyzed on AEAMP. Alloxan monohydrate (150 mg/kg b.w) was used to induce diabetes in the rats. 150 mg/kg b.w positive control group doses of 6.67, 13.53, and 27.06 mg/kg were administered to 3 groups for twenty-one days. The positive control group was administered 30 mg/kg of metformin. The negative and normal control groups were administered distilled water. The fasting blood glucose, serum insulin, lipid profile, inflammatory cytokines, antioxidant markers, carbohydrate metabolizing enzymes, and liver glycogen were analyzed as well as PI3K/AKT and apoptotic markers PCNA and Bcl2 by RT-PCR. RESULTS: AEAMP inhibited α-amylase and α-glucosidase enzymes more effectively than acarbose. AEAMP reduced FBG levels, HOMA-IR, G6P, F-1,6-BP, MDA, TG, TC, AI, CRI, IL-6, TNF-α, and NF-κB in diabetic rats. Furthermore, in diabetic rats, AEAMP improved serum insulin levels, HOMA-ß, hexokinase, CAT, GST, and HDL-c. Liver PI3K, liver PCNA and pancreas PCNA were not significantly different in untreated diabetic rats when compared to normal rats suggesting alloxan induction of diabetes did not downregulate the mRNA expression of these genes. AEAMP significantly up-regulated expression of AKT and Bcl2 in the liver and pancreatic tissue. It is interesting that luteolin and resorcinol were among the constituents of AEAMP. CONCLUSIONS: AEAMP can improve ß-cell dysfunction by upregulating liver AKT and pancreatic PI3K and AKT genes, inhibiting carbohydrate metabolizing enzymes and preventing apoptosis by upregulating liver and pancreatic Bcl2. However, the potential limitation of this study is the unavailability of equipment and techniques for collecting more data for the study.

Pharmacological effects of novel microvesicles of basil, on blood glucose and the lipid profile: a preclinical study.

Microencapsulation represents a process that can create targeted, controlled release kinetics of drugs, thus optimizing therapeutic efficacy. Our group has investigated the impact of this technology on Wistar rats to determine pharmacological efficacy of basil extracts. Animals were treated with water extract of Ocimum basilicum in microvesicles and with combination of basil extracts and 3α,7α-dihydroxy-12-keto-5-cholanate, also known as 12-monoketocholic acid (MKC) acid in microvesicles for 7 days. Alloxan was used to induce hyperglycemia. Pharmacological effects on glycemia were evaluated by measuring blood glucose levels in alloxan-induced diabetic rats. Microvesicles were prepared using the Büchi-based microencapsulating system developed in our lab. The dose of basil extract that was orally administered in rats was 200 mg/kg and the dose of MKC acid was 4 mg/kg as per established protocols. A seven-day treatment with basil aqueous extract, as well as a combination of basil and MKC acid extract in the pharmaceutical formulation, led to a statistically significant reduction in the blood glucose concentration of animals with alloxan-induced hyperglycemia compared to pre-treatment values (p < 0.05 and p < 0.01), which indicates that basil has hypoglycemic and antihyperglycemic effects. Microvesicles, as a pharmaceutical-technological formulation, substantially enhance the hypolipidemic action of basil extract with MKC acid.

Streblus asper attenuates alloxan-induced diabetes in rats and demonstrates antioxidant and cytotoxic effects.

CONTEXT: Streblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation. OBJECTIVE: The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper. MATERIALS AND METHODS: Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay. RESULTS: Methanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: The methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.

Passiflora edulis Leaf Extract: Evidence of Antidiabetic and Antiplatelet Effects in Rats.

Different Passiflora species have been appointed as a promising herbal medicine due to antioxidant properties; however, their effect on oxidative process induced by diabetes is still controversial. We aimed to evaluate effects of hydroethanolic extract 70% from P. edulis leaf on biochemical blood markers, collagen glycation, production of oxidant species and platelet aggregation in diabetic rats. The phytochemical analysis of the extract was performed by dereplication using LC coupled to the Photodiode Array Detector and Mass Spectrometer detector. Male Wistar rats were assigned to the control group and groups treated with alloxan (150 mg/kg) intraperitoneally, extract (200 mg/kg/d, for 90 d) and combination of alloxan and extract. The phytochemical analysis suggested the presence of flavonoids C-glycosides in the extract. The diabetic animals treated with the extract presented improvement in glycaemic control, reduced glycation collagen, levels of non-high density lipoprotein (non-HDL) cholesterol, total cholesterol and creatinine, production of oxidant species and aggregation in platelet in relation to diabetic animals non-treated. Our results showed that P. edulis leaf extract presents a health benefit to the diabetic state, preventing the appearance of its complications. Its effect can be associated with flavonoids, among which is the flavonoid C-glycoside isoorientin.

Berberis lycium Royle. extracts attenuate inflammation and modulates hyperglycemia in alloxan induced diabetic rats.

Berberis lycium Royle (Berberidaceae) is traditionally used for the treatment of diabetes mellitus. Present study was conducted to determine the antioxidant, antidiabetic and anti-inflammatory effects of aqueous and methanolic whole plant extracts. Total phenolic contents were determined by Folin-ciocalteu method whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) method. In vitro anti-diabetic activity was determined using alpha amylase assay. Acute hypoglycemic activity was investigated on normoglycemic rats. Sub-acute anti-diabetic effects were investigated in alloxan induced diabetic rats for 14 days. Methanolic extract exhibited 183.5±1 mg/g Gallic acid equivalent (GAE) phenolic contents. The methanolic extract exhibited an IC50 of 242µg/mL and 37.26 mg/mL in antioxidant and alpha amylase inhibitory assays respectively. Administration of methanolic extract in normoglycemic rats exhibited significant anti-hyperglycemic effect at 90 and 120 min. Methanolic extract (500 mg/kg extract) significantly reduced blood glucose at day 14. Methanolic extract (500 mg/kg) significantly reduced the concentration of tumor necrosis factor (TNF-α) and interleukin (IL-6) along with reduction in total cholesterol and triglyceride levels in diabetic rats. Administration of methanol extract also improved the hepatic markers. The study suggested that the methanolic extract possessed antidiabetic effect that might be attributed to its alpha amylase, antioxidant and anti-inflammatory potential.

Regulating role of ethyl acetate fraction of Tephrosia tinctoria pers. in carbohydrate metabolism and oxidative stress in diabetic rats.

Traditionally, Tephrosia tinctoria (TT) is used as antimicrobial, larvicidal, antidiabetic and antioxidant agents. In the present study, the diabetes was induced in male albino - rats using alloxan (140 mg/kg b.w.) and treated with ethyl acetate extract (100 and 200 mg/kg b.w.) of T. tinctoria (TTEA) orally for 28 days. The effects of TTEA on biochemical paramets were studied. The results of this comprehensive study revealed that the TTEA significantly restored the altered parameters in alloxan-induced diabetic rats. The diabetes-induced elevated levels of glycogenolysis and gluconeogenesis metabolism were significantly controlled by TTEA. In the same, the decreased glycogenesis, glycolysis and TCA cycle metabolisms were significantly increased by TTEA. The enzymatic and non- enzymatic antioxidant levels were significantly elevated in TTEA treated diabetic rats and also the total non-enzymatic antioxidants capacity of serum and liver homogenate were calculated though DPPH inhibition. To conclude, this study demonstrates the anti-diabetic effect of TTEA possibly mediated through regulating carbohydrate metabolism and antioxidant status.

Antidiabetic role of a novel protein from garlic via NO in expression of Glut-4/insulin in liver of alloxan induced diabetic mice.

INTRODUCTION: Garlic has been reported to stimulate nitric-oxide (NO) synthesis in various cells. The role of aqueous-extract of garlic (AEG) and a purified NO-generating protein from garlic (NGPG) was investigated to control hyperglycemia by hepatic insulin synthesis through NGPG induced synthesis of NO via glucose-activated NO-synthase and glucose transporter-4 (Glut-4) in the hepatocytes. METHODS: Type-1-diabetic mellitus mice were prepared by alloxan treatment, NO was determined by methemoglobin method, insulin synthesis was quantitated by ELISA. TNF-α and NFκß was quantitated by ELISA. The AEG-induced Glut-4 synthesis was determined by in-vitro translation of mRNA from the hepatocytes. The NO-generating protein from AEG was purified to homogeneity by chromatography on DEAE-cellulose and Sephadex G-50 columns and sequenced/characterized by Mass-spectral-analysis. RESULTS: Purified NGPG injection to diabetic mice significantly reduced the blood-sugar and increase insulin level in diabetic animal. It also increases insulin-release, Glut-4 synthesis, glucose-uptake in both liver and ß-cells of diabetic mice. NGPG down regulated pro-inflammatory cytokine TNF-α and the stress responsive NFκB-expression in liver cell of diabetic mice. Injection of AEG to the diabetic mice reduced the blood glucose level from 550 ± 10 mg/dL to 125 ± 10 mg/dL in 16 h with simultaneous increase of plasma NO from 0 nmol/h to 2.5 nmol/h and insulin 2 ± 1.1µunit/mL to 15µunit/mL at 16 h. Oral administration of AEG to adult diabetic mice increased NO, insulin and Glut-4 synthesis in the hepatocytes. CONCLUSION: AEG and the purified-NGPG protein can control hyperglycemia through the stimulation of NO by glucose-activated NO-synthase that would play an important role in the synthesis of insulin/Glut-4 in liver-cells.

Chemical constituents of Cochlospermum regium (Schrank) Pilg. root and its antioxidant, antidiabetic, antiglycation, and anticholinesterase effects in Wistar rats.

The main physiological consequence of diabetes mellitus is chronic hyperglycemia. This condition is related to the formation of free radicals including advanced glycation end products (AGES) and to an increase in inflammatory processes. Cochlospermum regium (Schrank) Pilg., part of the Bixaceae family, is a cerrado plant known for its anti-inflammatory effects. The objectives of this study were to analyze the constituent compounds of C. regium roots and to evaluate the antioxidant, antiglycation, antidiabetic, and anticholinergic effects of its hydromethanolic extract through in vitro and in vivo experimental models. The presence of phenols, flavonoids, condensed tannins, and flavonols was analyzed by liquid chromatography - photodiode array (LC/PDA) analysis. Whereas antioxidant activity was investigated via DPPH, ABTS, ß-carotene/linoleic acid, and malondialdehyde colorimetric assays. Inhibition of AGEs was examined via a bovine serum albumin system whose glycosylating agent was glucose. Antidiabetic potential was examined in normoglycemic Wistar rats that received glucose overload, in alloxan-induced diabetic rats, and in rats that received a hyperglycemic diet. Disaccharidase inhibition was assessed using in vitro and in vivo methods, as was acetylcholinesterase (AChE) inhibition in brain structures. The hydromethanolic extract (CRHE) possessed a high concentration of phenolic compounds and showed antioxidant effects. The LC-DAD results revealed that CRHE contained a high concentration of phenolic acids and the majority was gallic acid. Treatment with CRHE caused significant inhibition of AGE formation. The oral glucose tolerance test (OGTT) in normoglycemic animals showed a reduction in blood glucose levels after treatment with 100 mg/kg CHRE, accompanied by an increase in hepatic glycogen content. There was also a significant reduction in the fasting glucose levels of alloxan-induced diabetic animals after 7 days of treatment with daily doses of 100 mg/kg. After 14 weeks of hyperglycemic diet, the last four or which were combined with 100 mg/kg CRHE treatment, there was a decrease in blood triglyceride levels. There was also a statistically significant decrease in the enzymatic activity of maltase, lactase and sucrase. The results demonstrate that oral administration of 30 and 100 mg/kg CRHE inhibited AChE activity in different brain structures. Thus, the extract of C. regium showed promising antioxidant, antiglycation, and antidiabetic effects that may be related to its high phenolic content.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Modulation of Oxidative Stress and Hyperglycemia by Rheum spiciformis in Alloxan Induced Diabetic Rats and Characterization of Isolated Compound.

This study evaluates the ameliorative potential of Rheum spiciformis methanolic (RS-MeOH) extract in reducing oxidative stress and hyperglycemia in albino rats along with characterization of possible therapeutic compound(s). Groups treated with 50 and 100 mg/kg bw plant extract (RS-MeOH ) decrease blood glucose levels from 359.9±8.2 to 209.5±8.5 mg/dl (50 mg/kg bw) and 354.7±13.3 to 162.5±7.4 mg/dl (100 mg/kg bw) on the 0th and 14th day (P<0.001) respectively. This reduction in blood glucose was significant as compared to glibenclamide (20 mg/dl) which reduced glucose levels from 297.7±11.39 to 132.9±8.74 mg/dl on 0th and 14th day respectively. Biochemical parameters triglycerdies, cholesterol, low density lipoprotein (LDL) and creatinine were also reduced in a dose dependent manner. Liver marker enzymes were positively modulated by administration of RS-MeOH (P<0.001). Antioxidant enzyme profile showed an enhanced/better pattern after the administration of RS-MeOH extracts for reduced glutathione, reduced glutathione (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) in both liver and pancreas. Moreover pancreatic histopathology reports revealed ß-cell restorative effects with RS-MeOH, thereby potentiating its role in improving blood glucose levels. RS-MeOH purification and isolation studies involving GC-MS and NMR techniques revealed presence of emodin type compounds in RS-MeOH. Overall Rheum spiciformis showed ameliorative action on oxidative stress and hyperglycemia, however further studies to explore the mechanism of action of possible therapeutic compound in invivo clinical trials will prove beneficial for the advancement of new oral antidiabetic drug.

Evaluation of antidiabetic activity of Ipomoea batatas L. extract in alloxan-induced diabetic rats.

Different allopathic drugs are being used for the treatment of diabetes mellitus but more emphasis are being placed on the use of medicinal plants, herbs, and natural extracts of fruits and vegetables due to their easy availability, easy consummation with low cost, and with no well-reported side effects. White skinned sweet potato (WSSP; Ipomoea batatas L.) peel-off was selected to find out its antidiabetic potential as well as to explore the effects on selected biochemical parameters in diabetes-induced Wistar rats. In young (3-4 months) and old (up to 1 year) diabetic Wistar rats, it was found that WSSP ( I. batatas L.) peel-off significantly ( P < 0.05) decreased blood glucose level, protein glycation level, total cholesterol, triglycerides, and low-density lipoprotein (LDL)-cholesterol. A significant ( P < 0.05) increase in high-density lipoprotein (HDL)-cholesterol level after treatment was also reported. Furthermore, it was also found that WSSP peel-off also had beneficial effects on total protein concentration, albumin, globulin, and liver enzymes (serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). It might be concluded that antidiabetic potential of WSSP extract is due to the presence of bioactive compounds like glycoprotein, anthocyanins, alkaloids, and flavonoids, which act as insulin-like molecules or insulin secretagogues constituents in sweet potatoes peel-off and these antidiabetic proteins were extracted out in more concentration in methanol due to its organic nature. Further research is needed to purify and quantify the antidiabetic components responsible for antidiabetic effects of WSSP and it should be available in compact dose form for the treatment of diabetic patients.

Antidiabetic and antihyperlipidemic potential of ethanol extract of Salacia lehmbachii stem bark in alloxan-induced diabetic rats.

Background Salacial lehmbachii stem bark is used traditionally for the treatment of diabetes mellitus and its associated complications. Treatment of diabetes is necessary to reduce these complications. Methods In this study, the antidiabetic and antihyperlipidemic potential of S. lehmbachii ethanol stem bark extract was evaluated in alloxan-induced diabetic rats at a dose of 100 mg/kg, 200 mg/kg, and 400 mg/kg p.o. daily for 21 days. Blood glucose levels, serum total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) were assessed in the animals. Results Treatment of alloxan-induced diabetic rats with S. lehmbachii stem bark extract showed significant (p<0.01) reduction in blood glucose levels when compared with diabetic control. The elevated levels of serum cholesterol, triglycerides, LDL, and VLDL were significantly (p<0.01) reduced by S. lehmbachii stem bark extract, while the level of HDL significantly (p<0.01) increased. Conclusions The results obtained suggest that S. lehmbachii stem bark extract has the potential to treat diabetes condition and hyperlipidemic disorders.

Metabolic impairments and tissue disorders in alloxan-induced diabetic rats are alleviated by Salvia officinalis L. essential oil.

The current research explored for the first time the effect of Salvia officinalis L. (Sage) essential oil (EO) on Alloxan-induced diabetes in male Wistar rats. Sage EO was extracted by a Clevenger apparatus and analyzed by GC-FID and GC-MS. The most important chemical families identified in this oil were oxygenated monoterpenes (56.32%), hydrocarbon monoterpenes (15.00%) and hydrocarbon sesquiterpenes (14.70%). All treatments were administered orally. In vitro investigation showed that the EO had α-amylase and lipase inhibitory activities with IC50 = 38 µg/mL and IC50 = 52 µg/mL, respectively. In vivo experiments highlighted that the activities of serum α-amylase and lipase were reduced by 46.6% and 32.1%, respectively. Sage EO reduced glycemia by 60% and the level of glycogen stored in the liver by 43.7%. Treatments of diabetes with Sage EO significantly protected the liver function by lowering serum AST (35%), ALT (79%) and LDH (43%) activities. Furthermore, Sage EO was efficient to preserve the kidney function in diabetes by reverting back serum creatinine (47%) and UA (62.5%) concentrations to control values. The obtained results altogether evidenced that Sage EO had hypoglycemic and anti-obesity effects and could be a valuable complement in future diabetes therapy.

Therapeutic effect of vitamin B3 on hyperglycemia, oxidative stress and DNA damage in alloxan induced diabetic rat model.

Evidences in the form of experimental analysis and scientific investigations suggest that oxidative stress embody an imperative role in the onset and progression of type-2 diabetes mellitus (T2DM). Aberrant elevation in levels of free radicals, as observed upon disease onset, and the subsequent reduction in anti-oxidant defenses is pernicious to metabolic enzymes and cellular organelles. Niacin (Vitamin B3) is an essential nutrient for humans and is considered to be an important food additive for animals too. This research was conducted to examine the effect of nutraceutical antioxidant on diabetic environment. This important member of Vitamin B complex is a forerunner of nicotinamide adenine dinucleotide (NAD) and also nicotinamide adenine dinucleotide phosphate (NADP), both of them serving as coenzymes for several metabolic enzymes. This study reports the effects of niacin supplementation in alloxan induced diabetic rats divided into five groups. Diabetes induced rats were further treated with niacin at two doses (10 and 15 mg /kg body weight) and compared with a control set of diabetes without treatment. Niacin treatment showed recovery in almost all parameters in a dose reliant pattern. A notable decline in oxidative stress parameters with reductions in fasting blood glucose levels was observed. Histological studies reveal damage recovery in the liver as well as kidney tissues. A notable amount of recovery was observed in cellular DNA damage. As a deduction, it is advocated that dietary niacin supplementation might help in reducing problems associated with diabetes. A probable mechanism pertaining to the action of niacin is proposed as well.