Antihyperglycaemic and hypolipidaemic effects of the methanolic extract of Caralluma tuberculata in streptozotocin-induced diabetic rats

The antihyperglycaemic and hypolipidaemic effects of the methanolic extract of Caralluma tuberculata were investigated in streptozotocin (STZ)-induced diabetic rats. The antihyperglycaemic activity was assessed by the reduction in fasting blood glucose (54% at 4th week) and the peak of blood glucose at 120?min of an oral glucose tolerance test in diabetic rats. Further, the tested extract also increased plasma insulin by 206.8%. The hypolipidaemic action of the extract was evident by the significant decrease in the levels of total cholesterol, triglycerides and LDL-cholesterol by 41.5%, 36.7% and 49.1%, respectively, compared to diabetic rat values. Interestingly, the extract increased the cardio-protective lipid HDL-cholesterol by 147.97% as compared to diabetic rat value. The present data suggests that the methanolic extract of C. tuberculata has both antihyperglycaemic and hypolipidaemic effects in STZ-induced diabetic rats that may need further studies to be used in the management of diabetes and associated hyperlipedaemia.     

Harpagophytum procumbens extract potentiates morphine antinociception in neuropathic rats

The association of opioids and non-steroidal anti-inflammatory drugs, to enhance pain relief and reduce the development of side effects, has been demonstrated. Given many reports concerning the antinociceptive and anti-inflammatory effects of Harpagophytum procumbens extracts, the aim of our study was to investigate the advantage of a co-administration of a subanalgesic dose of morphine preceded by a low dose of H. procumbens to verify this therapeutically useful association in a neuropathic pain model. Time course, registered with the association of the natural extract, at a dose that does not induce an antinociceptive effect, followed by a subanalgesic dose of morphine showed a well-defined antiallodynic and antihyperalgesic effect, suggesting a synergism as a result of the two-drug association. H. procumbens cooperates synergistically with morphine in resolving hyperalgesia and allodynia, two typical symptoms of neuropathic pain. The results support the strategy of using an adjuvant drug to improve opioid analgesic efficacy.     

Increased expression of Galphaq protein in the heart of streptozotocin-induced diabetic rats

Heart disease is one of the major cause of death in diabetic patients, but the pathogenesis of diabetic cardio-myopathy remains unclear. In this experiment, to assess the significance of G protein signaling pathways in the pathogenesis of diabetic cardiomyopathy, we analyzed the expression of G proteins and the activities of second messenger dependent protein kinases: cAMP-dependent protein kinase (PKA), DAG-mediated protein kinase C (PKC), and calmodulin dependent protein kinase II (CaM kinase II) in the streptozotocin induced diabetic rat heart. The expression of Galphaq was increased by slightly over 10% (P<0.05) in diabetic rat heart, while Galphas, Galphai, and Gbeta remained unchanged. The PKA activity in the heart did not change significantly but increased by 27% (P<0.01) in the liver. Insulin treatment did not restore the increased activity in the liver. Total PKC activity in the heart was increased by 56% (P<0.01), and insulin treatment did not restore such increase. The CaM kinase II activity in the heart remained at the same level but was slightly increased in the liver (14% increase, P<0.05). These findings of increased expression of Galphaq in the streptozotocin-diabetic rat heart that are reflected by the increased level of PKC activity and insensitivity to insulin demonstrate that alteration of Galphaq may underlie, at least partly, the cardiac dysfunction that is associated with diabetes.     

Geraniin ameliorates streptozotocin-induced diabetic retinopathy in rats via modulating retinal inflammation and oxidative stress

BackgroundDiabetic retinopathy (DR) is the major complication of diabetes, which causes acquired vision loss in the working-age group population.ObjectiveHere, we planned to address the therapeutic roles of geraniin against the streptozotocin (STZ)-challenged DR in ratsMethodologyThe DR was induced in the animals by 60 mg/kg of STZ, and then treated with 25 mg/kg of geraniin for 60 days. Later, bodyweight, food consumption, and blood glucose levels were investigated. The levels of antioxidants, MMP-9, MCP-1, and VEGF, and inflammatory cytokine status were measured using marker-specific kits. The morphometric study was conducted to assess the retinal thickness. The pancreatic tissues were analyzed microscopically.ResultsGeraniin reduced the blood glucose (270.36 ± 81 mg/dL), hemoglobin, and enhanced bodyweight (261.93 ± 72 g)in the DR rats. The antioxidant levels in the STZ-challenged DR rats were substantially improved by geraniin. Geraniin also decreased inflammatory cytokines, MCP-I, MMP-9, and VEGF levels and enhanced the retinal thickness. A histological study demonstrated that geraniin reduced the pancreatic islet cell damage in STZ-induced DR rats.ConclusionOur outcomes witnessed that geraniin reduced retinal inflammation and oxidative stress in the STZ-induced DR rats.     

Chemical profile and antihyperlipidemic effect of Portulaca oleracea L. seeds in streptozotocin-induced diabetic rats

Hypolipidemic effect of Portulaca oleracea L. seed extract and its fractions have been studied on streptozotocin (STZ) at dose 75 mg/kg b.wt. After fractionation of the alcoholic extract; petroleum ether fraction was the most active fraction that decreased different hyperlipidemia biochemical parameters. After chromatographic analysis; oleamide, ethylpalmitate, β-amyrin, stigmasterol and β-sitosterol were identified. The GLC analysis of unsaponifiable matter revealed the presence of; lignoceric acid as a major constituent in the most bioactive fraction. In conclusion, petroleum ether fraction possessed a hypolipidemic effect in STZ-induced diabetic rats, which may be attributed to its phytosterols, fatty acid and amide compounds. The finding of the present investigation strongly demonstrates the potential of non-polar fraction of P. oleracea L. seed in combating hyperlipidemia in diabetic condition. So the petroleum ether fractions and its constituents can be used as hypolipdemic supplement in the developing countries towards the development of new therapeutic agents.     

Antihyperglycemic,antihyperlipidemic and antioxidative evaluation of compounds from Senna sophera (L.) Roxb in streptozotocin-induced diabetic rats

Senna sophera (L.) Roxb (Common name: Kasunda, Baner) (Leguminosae) is used as traditional medicine in Africa and Asia. The compounds were isolated from methanolic extract of leaves of Senna sophera (MFCS). Compound A was identified as Hexahydroxy diphenic acid and Compound B as Kaempferol. MFCS administration to diabetic rats exhibited significant reduction in the blood sugar level and showed gain in body weight. After the treatment of 100 mg/kg of MFCS, the blood sugar level was reduced to 52.33 ± 2.83 mg/dl in comparison to the blood sugar level of vehicle control 76.66 ± 3.17 mg/dl, whereas treatment with 50 mg/kg of MFCS reduced the blood sugar level slightly (72.33 ± 2.42 mg/dl). The daily continuous administration of MFCS for a period of 21 days normalised the serum lipid levels confirming the effect of MFCS on diabetic hyperlipidemia. Treatment with MFCS also reversed the activities of antioxidants, which could be a result of decreased lipid peroxidation.     

Determination of lipoprotein lipase activity in post heparin plasma of streptozotocin-induced diabetic rats by high-performance liquid chromatography with fluorescence detection

The activity of lipoprotein lipase (LPL), an enzyme responsible for lipoprotein metabolism, would vary in diseases and metabolic disorders. For determination of LPL activity, a highly sensitive high performance liquid chromatography (HPLC) method using a fluorescent reagent, 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ) was applied to determinate the oleic acid (OA) generated from triolein by LPL activity without multiple solvents extraction step. We studied the optimal conditions of the reaction including the effect of emulsifiers, deproteinizing solvents, and the concentration of bovine serum albumin (BSA). Ten millimolar concentrations of triolein, 5% of BSA, 1% of Gum arabic (GA), and acetonitrile showed the optimum conditions for measuring the LPL activity. The accuracy values for the determination of LPL activity in 10 microL of rat post heparin plasma were 108.73 approximately 114.36%, and the intra- and inter-day precision values were within 1.28% and 2.91%, respectively. The limit of detection was about 4.53 nM (signal-to-noise ratio 3). The proposed method was applied to determination of LPL activity in post heparin plasma of normal and streptozotocininduced diabetic rats associated with 52.3% reduction. The established assay system could be used for determining LPL activity in different physiological and pathological conditions to clarify the relationship between LPL activity and diabetes mellitus.     

核酸中碱基的氢键作用机理及电子特征理论研究

采用耦合簇量子化学方法 CCSD/aug-cc-pVDZ研究了嘧啶与嘌呤之间的相互作用,利用基函数叠加误差法(BSSE)消除相互作用能误差,并进行了几何结构优化;采用Gaussian 03程序包中的NBO程序分析了二阶稳定化能及自然键轨道.与此同时,应用约化密度函数(RDG)填色等值面图对体系进行了图形化分析,分析了氢键相互作用所在的空间位置和相对强度,以及氢键相互作用的性质,以进一步了解二者的相互作用.结果表明,嘧啶-嘌呤体系的相互作用属于闭合壳层静电相互作用.电子密度跃迁矩阵分析结果表明,激发区域主要集中在N原子和O原子处,涉及的空间广度很大,第一激发态主要涉及前线分子轨道,属于σ→π*或n→π*类型跃迁.     

Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin

The antiradical activity, protective effect against lipid peroxidation of liposomal membrane, and inhibitory effect on whole blood reactive oxygen species (ROS) liberation of Glycyrrhiza glabra crude extract and glycyrrhizin, its major compound, were assessed. The liquorice extract showed significant activity in all the three assay systems used in a dose dependent manner. It displayed remarkable reactivity with free stable 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, inhibitory efficacy in peroxidatively damaged unilamellar dioleoyl phosphatidylcholine (DOPC) liposomes, and inhibition of ROS chemiluminescence, generated by whole blood, induced by both receptor-bypassing stimuli (PMA) and receptor operating stimuli (Opz) in the ranking order of stimuli PMA> Opz. These activities may be attributed to phenolic antioxidants involving isoflavan derivatives, coumarins and chalcones. Nonetheless, triterpene saponin glycyrrhizin exhibited no efficacy in the system of DPPH reaction and peroxidation of liposomal membrane, and negligible inhibition of chemiluminescence generated by inflammatory cells. These results indicate that the mechanism of anti-inflammatory effect of glycyrrhizin most probably does not involve ROS and this major constituent is not responsible for the inhibition effects of liquorice extract on neutrophil functions.     

Evaluation of antiplasmodial properties of a cyanobacterium,Spirulina platensis and its mechanism of action

The rapid emergence of antimalarial drug resistance necessitates a continual effort on novel drug discovery. A cyanobacterium, Spirulina platensis, is a potential antimalarial agent that has been widely consumed as food supplement in the form of crude extract. It is known to possess antiviral, antibacterial and antifungi activities. This study examined the antimalarial activities of several Spirulina formulas against Plasmodium falciparum 3D7, in vitro. The tested Spirulina formulas included commercially available capsule, crude extract and alkaloid fraction. Results showed that all tested formula possessed antimalarial activities with the Spirulina capsule exhibited the highest activities (IC₅₀ = 2.16 μg/mL). Light and electron microscopies revealed interference of the Spirulina with the parasite hemozoin formation. In conclusion, all tested Spirulina formulas and fraction exhibited moderate to high antimalarial activities.     

Antihyperglycaemic effects of ethanol extracts of Carica papaya and Pandanus amaryfollius leaf in streptozotocin-induced diabetic mice

Diabetes mellitus is a global disease that is increasing in an alarming rate. The present study was undertaken to study the antidiabetic effect of the ethanol extracts of Carica papaya and Pandanus amaryfollius on streptozotocin-induced diabetic mice. The results of the present study indicated that there was no significant difference in the body weight of the treated groups when compared to diabetic control. Whereas, there was significant (P?相似文献   

Effect of Tridax procumbens (Linn.) on bile duct ligation-induced liver fibrosis in rats

The present study was undertaken to clarify whether methanolic extract of Tridax procumbens prevents liver fibrosis in rat. The hepatic fibrosis was induced by 28 days of bile duct ligation in rats. The 4-week treatment with Tridex procumbens reduced the serum aspartate aminotransferase (U?L?1), glutamate pyruvate transaminase (U?L?1), alkaline phosphatase (IU?L?1), lactate dehydrogenase (IU?L?1), total bilirubin (mg?dL?1), direct bilirubin (mg?dL?1) and hydroxyproline (mg?gm?1) content in liver and improved the histological appearance of liver section. The results of this study led us to conclude that T. procumbens can reduce the degree of hepatocellular damage and may become antifibrotic agent for liver fibrosis.     

A validated high-performance thin-layer chromatography method for the quantification of chlorogenic acid in the hydroalcoholic extract of Gynura cusimbua leaves

JPC – Journal of Planar Chromatography – Modern TLC - A simple, reliable, and reproducible high-performance thin-layer chromatography (HPTLC) method was developed for the quantitative...     

Daptomycin structure and mechanism of action revealed

Daptomycin kills otherwise antibiotic-resistant gram-positive pathogens and is the first lipopeptide antibiotic to reach the clinic. Elucidation of its 3D structure and mechanism of action, reported in this issue of Chemistry & Biology, will facilitate the design and engineering of new, potentially life-saving antibiotics.     

Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide

Dimethyl sulfoxide (DMSO) is a small amphiphilic molecule which is widely employed in cell biology as an effective penetration enhancer, cell fusogen, and cryoprotectant. Despite the vast number of experimental studies, the molecular basis of its action on lipid membranes is still obscure. A recent simulation study employing coarse-grained models has suggested that DMSO induces pores in the membrane (Notman, R.; Noro, M.; O'Malley, B.; Anwar, J. J. Am. Chem. Soc. 2006, 128, 13982-13983). We report here the molecular mechanism for DMSO's interaction with phospholipid membranes ascertained from atomic-scale molecular dynamics simulations. DMSO is observed to exhibit three distinct modes of action, each over a different concentration range. At low concentrations, DMSO induces membrane thinning and increases fluidity of the membrane's hydrophobic core. At higher concentrations, DMSO induces transient water pores into the membrane. At still higher concentrations, individual lipid molecules are desorbed from the membrane followed by disintegration of the bilayer structure. The study provides further evidence that a key aspect of DMSO's mechanism of action is pore formation, which explains the significant enhancement in permeability of membranes to hydrophilic molecules by DMSO as well as DMSO's cryoprotectant activity. The reduction in the rigidity and the general disruption of the membrane induced by DMSO are considered to be prerequisites for membrane fusion processes. The findings also indicate that the choice of DMSO concentration for a given application is critical, as the concentration defines the specific mode of the solvent's action. Knowledge of the distinct modes of action of DMSO and associated concentration dependency should enable optimization of current application protocols on a rational basis and also promote new applications for DMSO.     

Cardiovascular effects of mycelium extract of Ganoderma lucidum: inhibition of sympathetic outflow as a mechanism of its hypotensive action

In an effort to understand the mechanism of cardiovascular actions of Ganoderma lucidum which was cultivated in Korea, the mycelium was isolated for a large-scale culture. Water extract of the mycelia was evaluated for its cardiovascular activity in anesthetized rabbits and rats. The left femoral artery and vein were cannulated for the measurement of arterial pressure and subsequent delivery of drugs. The left kidney was exposed retroperitoneally and a branch of the renal nerve was used to integrate renal efferent or afferent nerve activities. The extract decreased systolic and diastolic blood pressure, which was accompanied by an inhibition of renal efferent sympathetic nerve activity. The extract did not decrease heart rate in these animals, although there was clear hypotension in the extract dose dependent manner. This suggests that the hypotension induced by the treatment of the extract was secondary to the primary effect of the extract in the central nerve system, which suppressed the sympathetic outflow. Therefore we concluded that the mechanism of hypotensive action of Ganoderma lucidum was due to its central inhibition of sympathetic nerve activity.     

Absorption,transport and insulin-mimetic properties of bis(maltolato)oxovanadium (IV) in streptozotocin-induced hyperglycemic rats by integrated mass spectrometric techniques

The use of V(IV) complexes as insulin-enhancing agents has been increasing during the last decade. Among them, 3-hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven to be especially suitable as ligands for vanadyl ions. In fact, they have passed phase I and phase II clinical trials, respectively. However, the mechanism through which those drugs exert their insulin-mimetic properties is still not fully understood. Thus, the aim of this study is to obtain an integrated picture of the absorption, biodistribution and insulin-mimetic properties of the bis(maltolato)oxovanadium (IV) (BMOV) in streptozotocin-induced hyperglycaemic rats. For this purpose, BMOV hypoglycaemic properties were evaluated by monitoring both the circulating glucose and the glycohemoglobin, biomarkers of diabetes mellitus. In both cases, the results were drug concentration dependent. Using doses of vanadium at 3 mg/day, it was possible to reduce the glycaemia of the diabetic rats to almost control levels. BMOV absorption experiments have been conducted by intestinal perfusion revealing that approximately 35% of V is absorbed by the intestinal cells. Additionally, the transport of the absorbed vanadium (IV) by serum proteins was studied. For this purpose, a speciation strategy using high-performance liquid chromatography (HPLC) for separation and inductively coupled serum mass spectrometry, ICP-MS, for detection has been employed. The obtained HPLC-ICP-MS results, confirmed by MALDI-MS data, showed evidence that V, administered orally, is uniquely bound to transferrin in rat serum.     

Study of the mechanism action of sodium gluconate used for the protection of scale and corrosion in cooling water system

This work based on the mechanism action study of sodium gluconate (SG) for ordinary mild steel used for cooling water system treatment. In the first time, we evaluated the temperature effect on the scale inhibition of SG using statistic scale inhibition method. Result showed that the inhibition efficiency became more important with increasing temperature, at great concentration (10⁻² and 10⁻³ M). This can be explained by forming of stable complex SG–Ca²⁺. In the second time, the present work focuses on the study of operational parameters and corrosion products effect on SG performance using potentiodynamic polarization and electrochemical impedance spectroscopic method. The obtained results show that SG is a very good inhibitor for corrosion and scale and remains effective in the presence of corrosion products. For this study we were proposed a mechanism action for SG on metallic surface. In addition, the SG keeps its effectiveness in a more aggressive medium such as 3% NaCl. Finally, to complete the formulation, we added a not oxidizing biocide (CTAB) to SG. The results obtained show that SG remains its effective.