Effect of chronic administration of Boerhaavia diffusa Linn. leaf extract on experimental diabetes in rats

Purpose: The root and aerial parts of Boerhaavia diffusa Linn. (Nyctaginaceae) were used in Ayurveda for the treatment of diabetes. The present study is aimed at evaluating the antidiabetic activity of chloroform extract of Boerhaavia diffusa leaves on chronic administration in streptozotocin-induced non-insulin-dependent diabetes mellitus (NIDDM) model diabetic rats. Methods: The blood glucose lowering activity of the leaf extract was studied in streptozotocin-induced (65 mg/kg, i.v.) NIDDM model diabetic rats after oral administration of the extract at daily doses of 50, 100 and 200 mg/kg body weight for four weeks and compared with glibenclamide. Blood samples were collected from the tail vein before and also at weekly intervals for four weeks from the first dose of drug administration and blood glucose was analyzed by glucose-oxidase method using a visible spectrophotometer. Results: The leaf extract of B. diffusa produced dose-dependent reduction in blood glucose in streptozotocin-induced NIDDM rats comparable to that of glibenclamide. The results indicate that the reduction in blood glucose produced by the extract is probably through rejuvenation of pancreatic b-cells or through extrapancreatic action. Conclusion: The chloroform extract of Boerhaavia diffusa has significant antidiabetic activity and this supports the traditional usage of the plant by Ayurvedic physicians for the control of diabetes. Keywords: Blood glucose, Boerhaavia diffusa, Diabetes mellitus Streptozotocin, Rats> Tropical Journal of Pharmaceutical Research Vol. 3 (1) 2004: pp. 305-30

High levels of shading as a sustainable application for mitigating drought, in modern apple production

The sustainability of reducing light in apple orchards under well-watered (ww) and water stress (ws) conditions was evaluated for water relations, plant gas exchanges, fruit growth, yield determinants, and fruit quality over three years. A black (B) 28% shading net was compared with two different 50% shading nets: red (R) and white (W). Each net was combined with two irrigation regimes (ww and ws) based on plant water status. Under ww and ws conditions, increasing shade from 28% to 50% was not detrimental for plant gas exchanges, yield, or quality over three years. Higher shade improved plant water status regardless of irrigation regime. Higher shading could be considered sustainable in apple orchards over several seasons. Fruit quality was more sensitive to plant water status than to light reduction. ws increased fruit soluble solid content and relative dry matter, regardless of shading, and this was positively reflected in consumer’s preference. When water availability is limited, increasing shading to 50% can help save water and maintain high-quality yields associated with water stress. Given the likely reductions of water availability in agriculture, growers and consultants may consider shading apple orchards as a sustainable and safe horticultural technique to save water

Kiwi 4.0: In Vivo Real-Time Monitoring to Improve Water Use Efficiency in Yellow Flesh Actinidia chinensis

This manuscript reports the application of sensors for water use efficiency with a focus on the application of an in vivo OECT biosensor. In two distinct experimental trials, the in vivo sensor bioristor was applied in yellow kiwi plants to monitor, in real-time and continuously, the changes in the composition and concentration of the plant sap in an open field during plant growth and development. The bioristor response and physiological data, together with other fruit sensor monitoring data, were acquired and combined in both trials, giving a complete picture of the biosphere conditions. A high correlation was observed between the bioristor index (Delta I-gs), the canopy cover expressed as the fraction of intercepted PAR (fi_PAR), and the soil water content (SWC). In addition, the bioristor was confirmed to be a good proxy for the occurrence of drought in kiwi plants; in fact, a period of drought stress was identified within the month of July. A novelty of the bioristor measurements was their ability to detect in advance the occurrence of defoliation, thereby reducing yield and quality losses. A plant-based irrigation protocol can be achieved and tailored based on real plant needs, increasing water use sustainability and preserving high-quality standards

Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna (L.) in anaesthetized dogs

BACKGROUND: The bark of Terminalia arjuna L. (Combretaceae) is used in Ayurveda since ancient times for the treatment of cardiac disorders. Previous laboratory investigations have demonstrated the use of the bark in cardiovascular complications. The present study was aimed to find the effect of 70% alcoholic extract of Terminalia arjuna on anaesthetized dog blood pressure and probable site of action. METHODS: Six dogs were anaesthetized with intraperitoneal injection of thiopental sodium and the blood pressure of each dog (n = 6) was measured from the left common carotid artery connected to a mercury manometer on kymograph. The femoral vein was cannulated for administration of drug solutions. The extract of T. arjuna (dissolved in propylene glycol) in the dose range of 5 to 15 mg/kg were administered intravenously in a pilot study and the dose (6 mg/kg) which produced appreciable hypotension was selected for further studies. RESULTS: Intravenous administration of T. arjuna produced dose-dependent hypotension in anaesthetized dogs. The hypotension produced by 6 mg/kg dose of the extract was blocked by propranolol but not by atropine or mepyramine maleate. This indicates that muscarinic or histaminergic mechanisms are not likely to be involved in the hypotension produced by the extract. The blockade by propranolol of the hypotension produced by T. arjuna indicates that the extract might contain active compound(s) possessing adrenergic ß(2)-receptor agonist action and/or that act directly on the heart muscle. CONCLUSION: The results indicated the likely involvement of peripheral mechanism for hypotension produced by the 70% alcoholic extract of Terminalia arjuna and lends support for the claims of its traditional usage in cardiovascular disorders

KCNQ1 Haplotypes Associate with Type 2 Diabetes in Malaysian Chinese Subjects

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10−5; OR = 1.9, P = 5.2 × 10−5; OR = 1.9, P = 7.8 × 10−5, respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10−11). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D

Renal defects in KCNE1 knockout mice are mimicked by chromanol 293B in vivo: identification of a KCNE1-regulated K+ conductance in the proximal tubule

The kidney plays a critical role in regulating body fluid volume and blood pressure by conserving ions, solutes and water. Knowing the processes that underpin the handling of ions, solutes and water by the kidney is essential to our understanding of fluid and blood pressure regulation. Movement of ions is mediated by specific transport proteins found in the membranes of kidney cells. These proteins are regulated by additional proteins, called accessory proteins. In the current study, we have examined the role of the accessory protein KCNE1 in regulating a channel, KCNQ1, which is important in kidney function. We have observed that in the absence of KCNE1 the kidney has difficulty conserving sodium, chloride and water. However, by using specific inhibitors of these proteins we have also determined that although KCNE1 has a role in kidney function, the mechanism of its action is unlikely to be by regulating the protein KCNQ1. Abstract KCNE1 is a protein of low molecular mass that is known to regulate the chromanol 293B and clofilium-sensitive K + channel, KCNQ1, in a number of tissues. Previous work on the kidney of KCNE1 and KCNQ1 knockout mice has revealed that these animals have different renal phenotypes, suggesting that KCNE1 may not regulate KCNQ1 in the renal system. In the current study, in vivo clearance approaches and whole cell voltage-clamp recordings from isolated renal proximal tubules were used to examine the physiological role of KCNE1. Data from wild-type mice were compared to those from KCNE1 knockout mice. In clearance studies the KCNE1 knockout mice had an increased fractional excretion of Na +, Cl -, HCO 3 - and water. This profile was mimicked in wild-type mice by infusion of chromanol 293B, while chromanol was without effect in KCNE1 knockout animals. Clofilium also increased the fractional excretion of Na +, Cl - and water, but this was observed in both wild-type and knockout mice, suggesting that KCNE1 was regulating a chromanol-sensitive but clofilium-insensitive pathway. In whole cell voltage clamp recordings from proximal tubules, a chromanol-sensitive, K +-selective conductance was identified that was absent in tubules from knockout animals. The properties of this conductance were not consistent with its being mediated by KCNQ1, suggesting that KCNE1 regulates another K + channel in the renal proximal tubule. Taken together these data suggest that KCNE1 regulates a K +-selective conductance in the renal proximal tubule that plays a relatively minor role in driving the transport of Na +, Cl - and HCO 3 -. © 2011 The Authors. Journal compilation © 2011 The Physiological Society

Antihypertensive Treatment Differentially Affects Vascular Sphingolipid Biology in Spontaneously Hypertensive Rats

We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A2, cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A2. This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR. Methods and Findings For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191±7 mmHg, losartan: 125±5 mmHg and hydralazine: 113±14 mmHg). The blood pressure lowering was associated with a 20–25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A2. The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction. Conclusion In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions

Variance of the SGK1 Gene Is Associated with Insulin Secretion in Different European Populations: Results from the TUEF, EUGENE2, and METSIM Studies

HYPOTHESIS:Serum- and Glucocorticoid-inducible Kinase 1 (SGK1) is involved in the regulation of insulin secretion and may represent a candidate gene for the development of type 2 diabetes mellitus in humans. METHODS:Three independent European populations were analyzed for the association of SGK1 gene (SGK) variations and insulin secretion traits. The German TUEF project provided the screening population (N = 725), and four tagging SNPs (rs1763527, rs1743966, rs1057293, rs9402571) were investigated. EUGENE2 (N = 827) served as a replication cohort for the detected associations. Finally, the detected associations were validated in the METSIM study, providing 3798 non-diabetic and 659 diabetic (type 2) individuals. RESULTS:Carriers of the minor G allele in rs9402571 had significantly higher C-peptide levels in the 2 h OGTT (+10.8%, p = 0.04; dominant model) and higher AUC(C-Peptide)/AUC(Glc) ratios (+7.5%, p = 0.04) compared to homozygous wild type TT carriers in the screening population. As interaction analysis for BMIxrs9402571 was significant (p = 0.04) for the endpoint insulin secretion, we stratified the TUEF cohort for BMI, using a cut off point of BMI = 25. The effect on insulin secretion only remained significant in lean TUEF participants (BMI< or =25). This finding was replicated in lean EUGENE2 rs9402571 minor allele carriers, who had a significantly higher AUC(Ins)/AUC(Glc) (TT: 226+/-7, XG: 246+/-9; p = 0.019). Accordingly, the METSIM trial revealed a lower prevalence of type 2 diabetes (OR: 0.85; 95%CI: 0.71-1.01; p = 0.065, dominant model) in rs9402571 minor allele carriers. CONCLUSIONS:The rs9402571 SGK genotype associates with increased insulin secretion in lean non-diabetic TUEF/EUGENE2 participants and with lower diabetes prevalence in METSIM. Our study in three independent European populations supports the conclusion that SGK variability affects diabetes risk