Investigation of the antioxidant and hypoglycemiant properties of Alibertia edulis (L.C. Rich.) A.C. Rich. leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Alibertia edulis (L.C. Rich.) A.C. Rich is a vegetable species used in Brazilian folk medicine due to it is putative hypoglycemiant effect but has never been pharmacologically investigated. It is popularly used for the control of diabetes, especially in the state of Mato Grosso, Brazil. Following confirmation of the antioxidant activity of A. edulis by Aquino et al. (2017), the aim of this study was to evaluate the effects of leaves of A. edulis aqueous extract (AEAE) on some biochemical parameters in mice fed a high-fat fed. MATERIAL AND METHODS: Leaves of A. edulis were air-dried in an oven at 40 °C for 10 days and ground into a fine powder by mechanical milling. The AEAE was prepared by decoction (1:10 w/v) at 97 °C for 15 min, and later filtered and lyophilized. Preliminary phytochemical analysis of the AEAE has been already indetified the presence of caffeic acid, quercetin 3-rhamnosyl-(1 â†’ 6)-galactoside and iridois ioxide, ferulic acid and rutin in decocted leaves (Aquino et al., 2017). In one experiment, the acute oral toxicity AEAE was evaluated at 2,000 mg/kg of body weight. The animals were observed periodically for 14 days. In second experiment, the animals were divided into four groups (n = 5): Control, AEAE 200, AEAE 400 mg/kg and positive control (Metformin 100 mg/kg). In a third experiment, animals were divided into: Control RC (standard diet) (n = 24) and Control HFF (high-fat fed) (n = 24) groups for induction of glucose intolerance. After eight weeks, they were further subdivided into six groups (n = 8 each) RC or HFF with or without AEAE at doses of 200 and 400 mg/kg (2-wk) treatments to assess glucose tolerance. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and expression of the antioxidant proteins of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and phosphorylated IKK were determined. RESULTS: The HF-fed animals developed glucose intolerance which the AEAE failed to revert. Meanwhile, the AEAE treatment did lower the glucose levels in the normolipidic cohorts by virtue of its antioxidant property. It was also observed that the treatment with the AEAE reduced food intake negatively interfering weight accretion. Beyond that, the treatment with AEAE interfered in the SOD and catalase expression and inhibited phosphorylation of IKK thus suggesting that the observed hypoglycemiant power may be related to its known antioxidant potential. No sings of toxicity or hemolysis were detectaed at indicating that, at the concentrations evaluated, the extract was not toxic to normal cells. CONCLUSION: The AEAE showed a hypoglycemiant effect in the normolipidic mice that received the control diet, but not in those that were made glucose-intolerant by consuming a high-fat fed. The extract also exhibited substantial protection against hemolysis and oxidative stress. Moreover, no signs of toxicity were evident at 2000 mg/kg of body weight.

Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review.

Interest in the heat shock proteins (HSPs), as a natural physiological toolkit of living organisms, has ranged from their chaperone function in nascent proteins to the remedial role following cell stress. As part of the defence system, HSPs guarantee cell tolerance against a variety of stressors, including exercise, oxidative stress, hyper and hypothermia, hyper and hypoxia and improper diets. For the past couple of decades, research on functional foods has revealed a number of substances likely to trigger cell protection through mechanisms that involve the induction of HSP expression. This review will summarize the occurrence of the most easily inducible HSPs and describe the effects of dietary proteins, peptides, amino acids, probiotics, high-fat diets and other food-derived substances reported to induce HSP response in animals and humans studies. Future research may clarify the mechanisms and explore the usefulness of this natural alternative of defense and the modulating mechanism of each substance.

Impact of Trans-Fats on Heat-Shock Protein Expression and the Gut Microbiota Profile of Mice.

Partially hydrogenated oils are known to cause metabolic stress and dyslipidemia. This paper explores a new dimension about the interaction between dietary trans-fats and the defense heat-shock protein (HSP) system, inflammation, and the gut microbiota of mice consuming a hyperlipidic diet containing partially hydrogenated vegetable oil free of animal fat. Five diet groups were installed: control diet, 2 hyperlipidic-partially hydrogenated-oil diets, each containing either casein or whey-protein hydrolysate (WPH) as protein source, and 2 consuming hyperlipidic-unhydrogenated-oil diets containing either WPH or casein as a protein source. The partially hydrogenated oil inhibited c-Jun NH2 -terminal kinase phosphorylation in the casein diets, but without altering κ-B kinase. Neither the lipid nor the protein had an influence on the proinflammatory toll-like receptor 4 (TLR4) pathway, but the combination of the high-lipid content and WPH impaired glucose tolerance without altering insulin or glucose transporter-4 translocation. It was remarkable to observe that, contrary to the case of a common high-fat diet, the lard-free hyperlipidic diets were hardly able to invert the Bacteroidetes:Firmicutes phylum ratio. Our results suggest that, in the absence of lard, the intake of trans-fatty acids is less harmful than expected because it does not trigger TLR4-inflammation or pose great threat to the normal gut microbiota. WPH had the effect of promoting the expression of HSP90, HSP60, and HSP25, but did not prevent dysbiosis, when the diet contained the unhydrogenated oil. The partially hydrogenated oil also seemed to antagonize the ability of WPH to induce the expression of protective HSPs.

Modulatory effects of arginine, glutamine and branched-chain amino acids on heat shock proteins, immunity and antioxidant response in exercised rats.

Heat shock proteins (HSPs) are endogenous proteins whose function is to maintain the cell's tolerance to insult, and glutamine supplementation is known to increase HSP expression during intense exercise. Since few studies have addressed the possibility that supplementation with other amino acids could have similar effects to that of glutamine, our objective was to evaluate the effects of leucine, valine, isoleucine and arginine as potential stimulators of HSPs 25, 60, 70 and 90 in rats subjected to acute exercise as a stressing factor. The immune markers, antioxidant system, blood parameters, glycogen and amino acid profile responses were also assessed. Male Wistar rats were divided into seven groups: control (rest, without gavage), vehicle (water), l-leucine, l-isoleucine, l-valine, l-arginine and l-glutamine. Except for the control, all animals were exercised and received every amino acid by oral gavage. Arginine supplementation up-regulated muscle HSP70 and HSP90 and serum HSP70, however, none of the amino acids affected the HSP25. All amino acids increased exercise-induced HSP60 expression, except for valine. Antioxidant enzymes were reduced by exercise, but both glutamine and arginine restored glutathione peroxidase, while isoleucine and valine restored superoxide dismutase. Exercise reduced monocyte, platelet, lymphocyte and erythrocyte levels, while leucine stimulated immune response, preserved the levels of the lymphocytes and increased leukocytes and maintained platelets at control levels. Plasma and muscle amino acid profiles showed specific metabolic features. The data suggest that the tissue-protecting effects of arginine could proceed by enhancing specific HSPs in the body.

Biotransformed citrus extract as a source of anti-inflammatory polyphenols: Effects in macrophages and adipocytes.

Chronic non-communicable diseases such as obesity are preceded by increased macrophage infiltration in adipose tissue and greater secretion of pro-inflammatory cytokines. We evaluated the anti-inflammatory potential of Biotransformed extract, and two control extracts: In Natura and Autoclaved. The assays were performed using a cellular model with RAW264.7, 3T3-L1 cells, and RAW264.7 and 3T3-L1 co-culture. The innovation of the study was the use of Biotransformed extract, a unique phenolic extract of a bioprocessed citrus residue. LPS stimulated RAW264.7 cells treated with the Biotransformed extract exhibited lower secretion of TNF-α and NO and lower protein expression of NFκB. In RAW264.7 and 3T3-L1 co-culture, treatment with 1.0mg/mL of the Biotransformed extract reduced secretion of TNF-α (30.7%) and IL-6 (43.4%). Still, the Biotransformed extract caused higher increase in adiponectin in relation to control extracts. When the co-culture received a LPS stimulus, the Autoclaved extract at 1.0mg/mL reduced IL-6 and TNF-α concentrations, and raised adiponectin. However, it was noteworthy that the Biotransformed extract was also able to significantly reduce IL-6 concentration while the Natural extract was not. The Biotransformed citrus extract evaluated in this study showed anti-inflammatory activity in macrophages and in co-culture, indicating that bioprocess of citrus residue can contribute to new product development with anti-inflammatory potential.

Chia (Salvia hispanica L.) enhances HSP, PGC-1α expressions and improves glucose tolerance in diet-induced obese rats.

OBJECTIVE: The aim of this study was to investigate the effects of chia seed and chia oil on heat shock protein (HSP) and related parameters in diet-induced obese rats. METHODS: Animals were divided in six groups: control, high-fat and high-fructose diet (HFF), and HFF with chia seed or chia oil in short (6-wk) and long (12-wk) treatments. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and proteins controlling oxidative energy metabolism were determined. The limit of significance was set at P < 0.05. RESULTS: The HFF diet induced glucose intolerance, insulin resistance, oxidative stress, and altered parameters related to obesity complications. The consumption of chia seed or chia oil did not reduce body weight gain or abdominal fat accumulation. However, chia seed and chia oil in both treatments improved glucose and insulin tolerance. Chia oil in both treatments induced expression of HSP70 and HSP25 in skeletal muscle. Short treatment with chia seed increased expression of HSP70, but not HSP25. Chia oil in both treatments restored superoxide dismutase and glutathione peroxidase expression. Extended treatment with chia seed and short treatment with chia oil restored peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression. CONCLUSION: Chia oil restored the antioxidant system and induced the expression of a higher number of proteins than chia seed. The present study demonstrated new properties and molecular mechanisms associated with the beneficial effects of chia seed and chia oil consumption in diet-induced obese rats.

Improvement of the physical performance is associated with activation of NO/PGC-1α/mtTFA signaling pathway and increased protein expressions of electron transport chain in gastrocnemius muscle from rats supplemented with L-arginine.

AIM: To examine the influence of l-arginine supplementation in combination with physical training on mitochondrial biomarkers from gastrocnemius muscle and its relationship with physical performance. MAIN METHODS: Male Wistar rats were divided into four groups: control sedentary (SD), sedentary supplemented with l-arginine (SDLA), trained (TR) and trained supplemented with l-arginine (TRLA). Supplementation of l-arginine was administered by gavage (62.5mg/ml/day/rat). Physical training consisted of 60min/day, 5days/week, 0% grade, speed of 1.2km/h. The study lasted 8weeks. Skeletal muscle mitochondrial enriched fraction as well as cytoplasmic fractions were obtained for Western blotting and biochemical analyses. Protein expressions of transcriptor coactivator (PGC-1α), transcriptor factors (mtTFA), ATP synthase subunit c, cytochrome oxidase (COXIV), constitutive nitric oxide synthases (eNOS and nNOS), Cu/Zn-superoxide dismutase (SOD) and manganese-SOD (Mn-SOD) were evaluated. We also assessed in plasma: lipid profile, glycemia and malondialdehyde (MDA) levels. The nitrite/nitrate (NOx(-)) levels were measured in both plasma and cytosol fraction of the gastrocnemius muscle. KEY FINDINGS: 8-week l-arginine supplementation associated with physical training was effective in promoting greater tolerance to exercise that was accompanied by up-regulation of the protein expressions of mtTFA, PGC-1α, ATP synthase subunit c, COXIV, Cu/Zn-SOD and Mn-SOD. The upstream pathway was associated with improvement of NO bioavailability, but not in NO production since no changes in nNOS or eNOS protein expressions were observed. SIGNIFICANCE: This combination would be an alternative approach for preventing cardiometabolic diseases given that in overt diseases a profound impairment in the physical performance of the patients is observed.