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.

Phytochemical Analysis and hypoglycemic potential of Filago hurdwarica (Wall. ex DC.) Wagenitz in alloxan induced diabetic mice.

Plants have profound therapeutic benefits, more economical treatments, fewer side effects, and a relatively cheap cost, making them a source of drugs for protective, preventative, curative, or conducive purposes and creating novel phytomedicines. Plant derived medicines are relatively safe compared to synthetic medicines. Many plants have proved to successfully aid in the treatment of diabetes including Filago hurdwarica (Wall. ex DC.) Wagenitz. The current investigations were therefore designed to assess the phytochemical, antioxidant, antidiabetic, and antihyperlipidemic activities of F. hurdwarica. The phytochemical investigations and antioxidant activities of different extracts were carried out using standard chemical tests, DPPH, and H2O2 scavenging assays. F. hurdwarica plant extract in Hydromethanolic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Swiss Albino mice were made diabetic by a single dose of alloxan (150 mg/kg). Hydromethanolic plant extract and fractions of F. hurdwarica were screened for antidiabetic activity and given to the alloxan-induced diabetic mice at a concentration of 150-250 mg/kg of body weight in different groups of 6 diabetic mice each orally once a day for 15 days. Glibenclamide is also given to another group to as a standard drug to support the result at a dose of 10 mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of mice were measured on 0, 4, 7, 11 and 15th days. The study found that the extract was safe up to the dose level of 2000 mg/kg and the dose response effect of chloroform extract (150-250 mg/kg) of F. hurdwarica showed expressive antihyperglycemic effects and also improved other altered biochemical parameters associated with diabetes. The FTIR and XRD spectra demonstrated the occurrence of phenols, alcohols, alkenes, alkyl halides, ketones, and aromatic compounds and confirmed the amorphous nature of the extract. GC-MS spectral analysis showed the tentative presence of 31 phytochemical constituents in the chloroform extract of F. hurdwarica with different retention time. To conclude, the chloroform extract (250 mg/kg) of F. hurdwarica revealed considerable antioxidant, antihyperglycemic, and antihyperlipidemic potential and is safe for treating diabetes and related complications.

Amelioration of hyperglycaemia and modulation of pro-inflammatory cytokines by Tamarix gallica fractions in alloxan induced diabetic rats.

Present study is engrossed in identification of phyto-constituents from aerial part extracts of Tamarix gallica and appraisal of its anti-oxidant, anti-diabetic and anti-inflammatory potential based upon its folktale use. The methanol and n-hexane fractions of aerial parts were analysed using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) respectively. Inhibitory concentration (IC50) showed better results in case of methanolic extract for both in antioxidant (IC50= 15.47 µg/mL) and alpha amylase (IC50=18.75 µg/mL) assays. Significantly higher quantities of phenolic and flavonoid contents were present in methanolic extract. A significant correlation was found to be existed between these contents and IC50 of antioxidant assay. Alloxan induced hyperglycaemia declined along with improvement in lipid profile, C-reactive proteins (CRP), liver function tests (LFTs) and renal function tests (RFTs). Methanolic fraction (500 mg/kg) was also related to significant reduction in levels of inflammatory markers i.e. tumour necrosis factor-alpha, TNF- α (1.28 ± 0.13 g/L) and interleukin-6, IL-6 (98 ± 10.4 pg/L) as observed in diabetic rats. Based upon the above findings, the study suggests that methanolic fraction from aerial parts of the T. gallica has better anti-diabetic profile which might be attributed to its alpha amylase, anti-oxidant and anti-inflammatory potential.

Metformin and Bee Venom: a Comparative Detection of Histological Alteration of the Pancreas and Systemic Inflammatory Markers in Diabetic Mice.

Metformin is the approved medication for managing global health issues concerning type 2 diabetes mellitus (T2DM). Using natural bioactive compounds as an alternative therapy is crucial to managing several metabolic diseases. Therefore, due to recent limited studies that detected the role of bee venom (BV) in improving diabetic conditions in Iraq, the current study was designed to identify the potential therapeutic role of BV and metformin in diabetic mice. Twenty male mice (Balb/c) aged about 60 days with an average weight of 26.55±2.70 g were randomly divided into four groups (n=5). The animals were placed in plastic cages for acclimatization for one week of access to food and water ad libitum. Overnight fasting was applied to 15 mice which were then injected with 95 mg/kg body weight of prepared alloxan. The mice were supplemented with glucose fluid for 3 days. On day 4, the blood was collected from the tail to measure the circulating glucose level. When blood glucose levels exceed 200 mg/dl, the animals are considered diabetic. After induction of diabetes, the animals were divided as follows: Control group: included five mice that were not subjected to diabetes induction; the animals in this group: did not receive any medications. Diabetic group: including five mice confirmed with diabetes without receiving any treatments. Metformin group: including five diabetic mice exposed to a single oral dose of 150 mg/kg of metformin for 30 days. Bee Venom group: including five diabetic mice exposed to a single intraperitoneal dose of 1 mg/kg Bee Venom for 30 days. After 30 days of treatment, blood was drained, and serum was obtained to detect the levels of glucose, insulin, TNFα, IL6, and IL10 by using precise enzyme-linked immunosorbent assay (ELIZA) kits. Also, the pancreas was collected from all mice for histopathological investigation. The result displayed significantly elevated glucose concentration in diabetic mice, while metformin and BV significantly reversed these increases. A significant decline in insulin concentration was seen in diabetic mice, whereas metformin and BV significantly enhanced this reduction in insulin concentration. Furthermore, mice treated with alloxan exhibited remarkable increases in TNFα and IL6 compared to control mice, while supplemented metformin and BV significantly reduced these high concentrations. Moreover, the level of IL10 markedly declined in diabetic mice, which was reversed significantly in response to metformin and BV. Histological detection of the pancreas in diabetic mice showed significant changes in the shape and size of islets associated with the arrangement and number of beta cells with a reduction of islets covering connective tissue. Metformin slightly restored these alterations; however, significant and remarkable restoring of histological changing was promoted by BV. Thus, BV could be a potential agent for managing metabolic disorders including diabetes.

Potential effect of Turbinaria decurrens acetone extract on the biochemical and histological parameters of alloxan-induced diabetic rats.

Upon Seeking natural and safe alternatives for synthetic medicines to treat many chronic diseases, seaweeds have offered a promising resource to produce numerous bioactive secondary metabolites. Through in vivo investigations, Turbinaria decurrens acetone extract (AE) revealed its antidiabetic activity against alloxan-induced diabetic rats. Treatment of rats with T. decurrens AE at 300 and 150 mg/Kg doses revealed antihyperglycemic activity by reducing the elevated blood glucose level. A remarkable decrease in the liver, kidney functions, and hyperlipidemia related to diabetes were also detected. Administration of the same extract also showed a recovery in body weight loss, total protein, albumin, and haemoglobin levels compared with untreated diabetic rats. Furthermore, treatment of rats with the same extract improved liver and pancreas histopathological disorders related to diabetes. These effects may be attributed to the presence of bioactive phytochemicals and antioxidant components in T. decurrens AE mainly cyclotrisiloxane, hexamethyl, and cyclic diterpene 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol alcohol). Besides, other valuable secondary metabolites, as phenols, flavonoids, alkaloids, terpenoids, steroid and glycosides, which were documented and published by the same authors in a previous study. The obtained results in the present study recommended using T. decurrens AE in developing medicinal preparations for treatment of diabetes and its related symptoms.

Adaptive responses to alloxan-induced mild oxidative stress ameliorate certain tauopathy phenotypes.

Oxidative stress is considered to promote aging and age-related disorders such as tauopathy. Although recent reports suggest that oxidative stress under certain conditions possesses anti-aging properties, no such conditions have been reported to ameliorate protein-misfolding diseases. Here, we used neuronal and murine models that overexpress human tau to demonstrate that mild oxidative stress generated by alloxan suppresses several phenotypes of tauopathy. Alloxan treatment reduced HSP90 levels and promoted proteasomal degradation of tau, c-Jun N-amino terminal kinase, and histone deacetylase (HDAC) 6. Moreover, reduced soluble tau (phosphorylated tau) levels suppressed the formation of insoluble tau in tau transgenic mice, while reduced HDAC6 levels contributed to microtubule stability by increasing tubulin acetylation. Age-dependent decreases in HDAC2 and phospho-tau levels correlated with spatial memory enhancement in alloxan-injected tau mice. These results suggest that mild oxidative stress, through adaptive stress responses, operates counteractively against some of the tauopathy phenotypes.

[Ulcerostatic effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacryl acid and its possible mechanisms]. / Ul'tserostaticheskii éffekt tris-[2-oksiétil] ammoniinoi soli zhelezosoderzhashchei poliakrilovoi kisloty i ego vozmozhnye mekhanizmy.

The study investigated a stimulating effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacryl acid on proliferative processes in the connective tissue in development of experimental gastric ulcer. The drug was found to exhibit an ulcerostatic effect, to change the levels of collagen, noncollagen proteins, glycosaminoglycan fractions, DNA and RNA.

[A biochemical analysis of the possible mechanisms of the ulcerostatic action of atranes]. / Biokhimicheskii analiz vozmozhnykh mekhanizmov ul'tserostaticheskogo deistviia atranov.

Stimulatory effect of metalloatrans on the development of stomach wall connective tissue components was examined in rats with experimental acetate ulcer. Metalloatrans were shown to inhibit peroxide oxidation processes of lipids in blood and stomach tissue.

[Possible mechanisms of anti-ulcer action of silatranes]. / K voprosu o vozmozhnykh mekhanizmakh ul'tserostaticheskogo deistviia silatranov.

A stimulating effect of methylethyl(silatrane-I-ilmethyl)-sulphonium iodides, 1-(ethoxy)silatranes and 1-(chloromethyl)silatrane on the processes of rat test acetate ulcer healing is studied. Silatranes efficiency is not inferior to oxyferriscorbone and exceeds that of methacil. It is shown that all preparations inhibit the processes of lipids peroxidation in the blood, in liposomes and stomach tissue.

[Antimalarial action of alloxan and 5,6-diamino-2,4-dihydroxy-pyrimidine in Plasmodium berghei].

Three hours after iv administration of alloxan and 5,6-diamino-2,4-dihydroxy-pyrimidine to mice infected with chloroquine-sensitive (CS) and chloroquine-resistant (CR) strains of Plasmodium berghei, the 2 compounds showed remarkable antimalarial actions. Parasitemia in CS and CR infected mice were reduced by about 50%. Slight hemolysis was seen in mice treated with alloxan but not in mice treated with 5,6-diamino-2,4-dihydro-pyrimidine. Alloxan did not inhibit glutathione reductase activity and no alloxan-glutathione complex was produced. No relationship between the antimalarial effects of alloxan and hemolysis or GSH content were found. It is suggested that the antimalarial effects of the two agents may be due to the inhibition of dihydroorotic acid dehydrogenase.

Improvement of disability and akinesia of patients with Parkinson's disease by intravenous iron substitution.

Akinetic crises are one of the problems arising in patients with Parkinson's disease in particular after long term treatment with levo-dihydroxyphenylalanine (L-DOPA). They are characterized by severe disability to move. Increasing dosages of L-DOPA and decarboxylase or monoaminooxidase inhibitors do not improve these symptoms. Intravenously applied iron in the form of a ferri-ferro-complex exhibits a considerable benefit for all patients treated so far. They regained a remarkable mobility. Their disability score dropped from up to 90 percent down to 30 percent. The effect is dosage-dependent, and withdrawal of iron will lead again to akinetic crises.

[Mechanism of formation of blocking factors and method of antiblocking immunotherapy in malignant tumors]. / O mekhanizme obrazovaniia blokiruiushchikh faktorov i metode antiblokiruiushchei immunoterapil zlokachestvennykh opukholei.

A hypothesis on blocking factor formation in carcinogenesis is discussed. Destabilisation of cell membranes and increased levels of proteolytic enzymes in tumor tissue are considered to be the trigger mechanism. Protease level in large bowel tumor was found to be higher than in normal tissue. Plasminogen level in cancer patients was significantly higher than in healthy subjects. Application of different experimental schemes of treatment with membrane-stabilizing drugs and an inhibitor of protease was followed by antitumor and antiblocking effects. Sorption of rheumatoid factor and immune complexes from plasma led to a decrease in the blocking activity of plasma in vitro. In cases of rectal cancer, plasmapheresis was followed by tumor regression and a fall in immune complex concentration.