Assessment of the Phytochemical Profile, Antioxidant Capacity, and Hepatoprotective Effect of Andrographis paniculata against CCl4-Induced Liver Dysfunction in Wistar Albino Rats.

Recent studies have highlighted the necessity to thoroughly evaluate medicinal plants due to their therapeutic potential. The current study delves into the phytochemical profile, antioxidant capacity, and hepatoprotective effect of Andrographis paniculata. The investigation specifically targets its effectiveness in mitigating liver dysfunction induced by carbon tetrachloride (CCl4) in Wistar albino rats, aiming to uncover its promising role as a natural remedy for liver-related ailments. A. paniculata leaf extract was screened for phytoconstituents and antioxidant and hepatoprotective effects in Wistar albino rats against CCl4-induced liver dysfunction. Phytochemical analysis revealed the presence of flavonoids, alkaloids, and phenolic compounds in all extracts. The phenolic concentration ranged from 10.23 to 19.52 mg gallic acid per gram of the sample, while the highest flavonoid concentration was found in the ethanol fraction (8.27 mg rutin equivalents per gram). The antioxidant activity varied from 10.23 to 62.23. GC-MS analysis identified several phytochemicals including octadecanoic acid, stigmasterol, phenanthrenecarboxylic acid, and others. Effects of the ethanol extract of A. paniculata were evaluated in four groups of animals. Biochemical estimations of serum glutamine oxaloacetate transaminase, serum glutamine pyruvate transaminase, and serum bilirubin were significantly higher (p < 0.05) in the CCl4-treated group. Treatment with 300 mg/kg b.w. of the ethanol extract of A. paniculata significantly (p < 0.05) decreased these serum enzymes. Lipid peroxidation levels in carbon tetrachloride-treated animals showed a substantial (p < 0.05) rise when compared to untreated animals, while the lipid peroxidation levels were considerably (p < 0.05) reduced after treatment with ethanol extract at 300 mg/kg b.w. Liver biochemical catalase activities were significantly reduced in the carbon tetrachloride-treated animals. The results of this study conclusively demonstrate that A. paniculata extracts are a rich source of phytochemicals and possess significant antioxidant, free radical scavenging, and hepatoprotective properties.

Mild hypothermia affects the morphology and impairs glutamine-induced anabolic response in human primary myotubes.

The specific impact of reduced temperature on skeletal muscle adaptation has been poorly investigated. Cold water immersion, one situation leading to decreased skeletal muscle temperature, is commonly proposed to reduce the perception of fatigue and muscle soreness after strenuous exercise. In contrast, it may impair long-term benefits of resistance exercise training on muscle strength and hypertrophy. To date, the physiological factors responsible for this blunted muscle adaptation remain unclear. Here, we used a cell culture model of human primary myotubes to specifically investigate the intrinsic behavior of muscle cells during mild hypothermia (MH). Newly formed myotubes were exposed to either 37°C or 32°C to evaluate the effect of MH on myotube size and morphology, protein synthesis, and anabolic signaling. We also compared the glutamine (GLUT)-induced hypertrophic response between myotubes incubated at 32°C or 37°C. We showed that 48 h exposure to MH altered the cellular morphology (greater myotube area, shorter myosegments, myotubes with irregular shape) and impaired GLUT-induced myotube hypertrophy. Moreover, MH specifically reduced protein synthesis at 8 h. This result may be explained by an altered regulation of ribosome biogenesis, as evidenced by a lower expression of 45S pre-ribosomal RNA and MYC protein, and a lower total RNA concentration. Furthermore, MH blunted GLUT-induced increase in protein synthesis at 8 h, a finding consistent with an impaired activation of the mechanistic target of rapamycin pathway. In conclusion, this study demonstrates that MH impairs the morphology of human myotubes and alters the hypertrophic response to GLUT.

The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment.

BACKGROUND: Our previous studies of Alzheimer's disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now expand our studies to a second neurodegenerative disease, ataxia-telangiectasia (A-T). Unlike AD, where clinically significant cognitive decline does not typically occur before age 65, A-T symptoms appear in early childhood and are caused exclusively by mutations in the ATM (A-T mutated) gene. RESULTS: Genetically ATM-deficient mice and wild type littermates were maintained with or without 4 % glutamine in their drinking water for several weeks. In ATM mutants, glutamine supplementation restored serum glutamine and glucose levels and reduced body weight loss. Lost neurophysiological function assessed through the magnitude of hippocampal long term potentiation was significantly restored. Glutamine supplemented mice also showed reduced thymus pathology and, remarkably, a full one-third extension of lifespan. In vitro assays revealed that ATM-deficient cells are more sensitive to glutamine deprivation, while supra-molar glutamine (8 mM) partially rescued the reduction of BDNF expression and HDAC4 nuclear translocation of genetically mutant Atm(-/-) neurons. Analysis of microarray data suggested that glutamine metabolism is significantly altered in human A-T brains as well. CONCLUSION: Glutamine is a powerful part of an organism's internal environment. Changes in its concentrations can have a huge impact on the function of all organ systems, especially the brain. Glutamine supplementation thus bears consideration as a therapeutic strategy for the treatment of human A-T and perhaps other neurodegenerative diseases.

Efficacy of Glutamine-Enriched Nutrition Support for Patients With Severe Acute Pancreatitis: A Meta-Analysis.

BACKGROUND: Plasma glutamine (Gln) level has been negatively correlated with the severity of severe acute pancreatitis (SAP). Although Gln is widely used today, the results of individual randomized controlled trials of Gln-enriched nutrition support for patients with SAP are conflicting. METHODS: PubMed, EMBASE, HighWire, Cochrane Central Register of Controlled Trials, Wanfang, China Journals Full-Text Database, and the Chinese Biomedical Literature Database were searched. Literature published before June 2014 was searched. Randomized controlled trials investigating the comparison of conventional and Gln-enriched nutrition support were included; a random effect model using Rev Man 5.2 software was chosen to complete this meta-analysis. The count data were analyzed using the risk ratio (RR) and 95% confidence interval (CI), and the measurement data were analyzed using the standard mean difference or weighted mean difference and 95% CI. Heterogeneity analyses were conducted by I(2) test; publication bias analyses were conducted by Begg test. RESULTS: Ten studies were eventually chosen for analysis, including 218 patients who received conventional methods (control group) and 215 patients who received Gln-enriched nutrition support (experimental group). Compared with the control group, Gln is helpful in elevating the albumin level, decreasing C-reaction protein (standard mean difference = 1.01, -1.89; 95% CI: 0.50 to 1.51, -3.23 to -0.56; P < .05), decreasing the incidence of infectious complication and mortality (RR = 0.62, 0.36; 95% CI: 0.46 to 0.83, 0.16 to 0.83; P < .05), and shortening the hospital stay length (weighted mean difference [WMD] = -3.89; 95% CI: -4.98 to -2.81; P < .05) without increasing expenses (WMD = -0.16; 95% CI: -1.34 to 1.02; P > .05). Intravenous infusion manifested more advantages by decreasing the incidence of infectious complications and mortality. CONCLUSIONS: Gln-enriched nutrition support is superior to conventional methods for SAP, and intravenous infusion may be a better choice for drug administration.

An economic approach to isotopic enrichment of glycoproteins expressed from Sf9 insect cells.

It is estimated that over half of all proteins are glycosylated, yet only a small number of the structures in the protein data bank are of intact glycoproteins. One of the reasons for the lack of structural information on glycoproteins is the high cost of isotopically labeling proteins expressed from eukaryotic cells such as in insect and mammalian cells. In this paper we describe modifications to commercial insect cell growth medium that reduce the cost for isotopically labeling recombinant proteins expressed from Sf9 cells. A key aspect of this work was to reduce the amount of glutamine in the cell culture medium while maintaining sufficient energy yielding metabolites for vigorous growth by supplementing with glucose and algae-derived amino acids. We present an analysis of cell growth and protein production in Sf9 insect cells expressing secreted Thy1-GFP fusion construct. We also demonstrate isotopic enrichment of the Thy-1 protein backbone with 15N and carbohydrates with 13C by NMR spectroscopy.

Oral glutamine supplementation decreases resting energy expenditure in children and adolescents with sickle cell anemia.

OBJECTIVES: To determine the effects of orally administered glutamine on the resting energy expenditure (REE) and nutritional status of children and adolescents with sickle cell anemia. METHODS: Twenty-seven children and adolescents (13 boys, 14 girls), 5.2 to 17.9 years old (median 11.0 years), received orally administered glutamine (600 mg/kg per day) for 24 weeks. Measures of REE and other nutritional parameters were compared at baseline and 24 weeks. RESULTS: After 24 weeks, the patients' median REE (kcal/d) decreased by 6% (P = 0.053) as indicated by the Harris Benedict equations and by 5% (P = 0.049) as indicated by the modified equations. Patients with less than 90% ideal body weight had even greater declines in REE after 24 weeks (P < 0.03 and 0.02, respectively). Improvements in nutrition parameters and in two amino acids in the plasma were observed. CONCLUSIONS: After 24 weeks of orally administered glutamine, children and adolescents with sickle cell anemia had a decrease in REE and improvement in nutritional parameters. Those who were underweight had a greater decrease in REE than those of normal body weight. Lowering REE may be an effective way to improve the growth of these children and adolescents.

Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats.

Glutamine (GLN) is a nonessential amino acid that is not included in current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1.1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations were significantly lower, in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared with both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) (p < .001). Corresponding results were found for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < .05), intestinal mucosa, and spleen as well as for plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of effects of amino acids and branched chain keto acids on leucine oxidation in human lymphocytes.

Effects of amino acids and branched chain keto acids on leucine transamination and oxidation were assessed in peripheral human lymphocytes. Isoleucine (80-200 mumol/l) and valine (250-500 mumol/l) diminished transamination and oxidation of leucine up to 25%, glutamine (50-1000 mumol/l) up to 55%. alpha-Ketoisocaproic acid (KIC; 200 mumol/l) augmented the activity state of branched chain keto acid dehydrogenase by 40%. It is concluded that in peripheral human lymphocytes (1) isoleucine, valine and glutamine are physiological inhibitors of leucine catabolism, and (2) leucine can promote its own degradation via KIC.