Ameliorative effects of aqueous extract from rosemary on oxidative stress and inflammation pathways caused by a high-fat diet in C57BL/6 mice.

Rosemary is an herb exhibits biological properties, attenuates inflammation, oxidative stress, and improves lipid profile. Here, we evaluated the effects of rosemary aqueous extract (RE) on mice fed with a high-fat diet (HFD). Male C57BL/6 mice were administered a control diet or HFD for 10 weeks. The treated groups received RE in the diet at different concentrations: 25, 250, and 500 mg/100 g. After 10 weeks, serum concentrations of glucose, lipid, insulin, leptin, adiponectin, and cytokines were evaluated and the oxygen radical absorbance capacity was determined. Histological analysis was performed to determine the concentrations of triacylglycerides (TG), total cholesterol, cytokines, and antioxidant enzymes as well as the expression of genes involved in lipid metabolism, oxidative stress, and inflammation. The dietary RE ameliorated HFD-induced weight gain, adipose tissue weight, glucose intolerance, and insulin, leptin, and free fatty acid levels. Reduction in hepatic TG deposition was observed. The levels of inflammatory cytokines decreased, and the expression of genes involved in lipid metabolism increased. RE mitigated oxidative stress and reduced the production of reactive oxygen species in HepG2 and 3T3-L1 cells. Therefore, RE is a potential therapeutic agent for the prevention of inflammation and oxidative stress outcomes associated with obesity.

Supplementation of vitamin D isolated or calcium-associated with bone remodeling and fracture risk in postmenopausal women without osteoporosis: A systematic review of randomized clinical trials.

Menopause and vitamin D deficiency increase bone reabsorption and bone fracture risk in women in postmenopause, and vitamin D supplementation may improve bone health and decrease bone fracture risk. This study aims to discuss the effect of vitamin D supplementation, isolated or calcium-associated, on remodeling and fracture risk bone in women in postmenopause without osteoporosis. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO database registration: CRD42022359796). A search was conducted in four databases and gray literature using MeSH and similar terms related to supplements, vitamin D, calcium, remodeling, and fracture bone, without the restriction of language and year of publication. A total of 3460 studies were identified, and nine were selected. Vitamin D supplementation increased 25-hydroxyvitamin D levels ≥10 ng/mL and decreased parathyroid hormone secretion dependent on baseline levels. The doses of 400 IU of vitamin D improved the percentage of carboxylated osteocalcin, whereas 800 to 1000 IU combined with calcium resulted in reduced, improved, or maintained bone mineral density and reduced alkaline phosphatase levels. However, 4000 IU alone or combined with calcium for 6 mo did not improve C-telopeptide and procollagen type 1 peptide levels. Additionally, 15 000 IU/wk increased the cortical area of metacarpal bone, whereas 500 000 IU of vitamin D annually for 5 y did not contribute to reducing the fracture risk and falls. Only one study found a reduction in fracture risk (dose of 800 IU of vitamin D plus 1200 mg of calcium). Thus, the vitamin D supplementation, alone or calcium-associated, improved the status of 25-hydroxyvitamin D and bone remodeling, but it was not possible to assert that it reduced fracture bone risk in postmenopausal women.

Anti-obesity properties and mechanism of action of flavonoids: A review.

Obesity is a major public health problem, and there is increasing scientific interest in its mechanisms, as well as a search for new compounds with antioxidant and anti-inflammatory properties that can minimize the metabolic complications associated with its pathology. One potential source of these compounds is natural products; Among these, flavonoids are a promising group of natural substances. Flavonoids are active constituents with diverse biological activities and are widely found in plants kingdom. Numerous studies have shown that flavonoids can effectively inhibit obesity and related metabolic disorders. The review synthesizes recent evidence in respect of progress in the understanding of the anti-obesity effects of flavonoids. Such effects which occurs through the modulation of proteins, genes and transcriptional factors involved in decreasing lipogenesis, increasing lipolysis, expenditure energy, stimulating fatty acids B-oxidation, digestion and metabolism of carbohydrates. In addition to mitigating inflammatory responses and suppress oxidative stress. A better understanding of the modulating effects and mechanisms of flavonoids in relation to obesity will allow us to better use these compounds to treat or even prevent obesity and its associated comorbidities.

Acute leucocyte, muscle damage, and stress marker responses to high-intensity functional training.

BACKGROUND: High-intensity functional training (HIFT) has become more popular, and the number of practitioners has increased; however, it remains unclear whether perturbations in the immune parameters occur, even after one single bout. Our aim was to examine acute leucocyte, muscle damage, and stress marker responses following a single 'Cindy' workout session, and compare the results between novice and experienced participants. MATERIAL AND METHODS: Twenty-three HIFT practitioners (age 31.0 ± 1.0 years) completed the 'Cindy' workout. They were categorized as novice (3-8 months of experience; n = 10) and experienced (≥18 months; n = 13). White blood cell (WBC) count, plasma creatine kinase (CK) activity, blood cortisol level, and lactate concentration were measured. Blood analysis was performed before (pre-ex), immediately after (post-ex), 30 min after (post-30 min), and 24 h after (post-24 h) a single 'Cindy' workout session. RESULTS: WBC count was higher post-ex (6.8 to 11.8x103/µL) and returned to baseline values within post-30 min (p<0.01). Neutrophil (3.3 to 4.5x103/µL) and lymphocyte levels (2.8 to 5.9x103/µL) were higher post-ex and returned to baseline values after post-24 h, yet lymphocytopoenia (2.2x103/µL) was observed at post-30 min (p<0.01). CK increased post-ex (174.9 to 226.7 U.L-1) and remained elevated post-24 h. Cortisol (14.7 to 17.0 µg/dL) and lactate (1.9 to 13.5 mmol.l-1) responses increased post-ex, but only the lactate level was reduced at post-30 min (p<0.01). The experienced participants had higher WBC, lymphocyte, and cortisol concentrations post-ex than the novice ones (p<0.01). CONCLUSIONS: A single HIFT session elicited significant acute perturbations in WBC count, stress markers, and muscle tissue, which is like other similar regimens. Importantly, the experienced participants showed greater lymphocyte and cortisol responses than the novice ones.

Effects of resistance training and turmeric supplementation on reactive species marker stress in diabetic rats.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a metabolic disease characterized by hyperglycemia and excessive generation of reactive oxygen species caused by autoimmune destruction of beta-cells in the pancreas. Among the antioxidant compounds, Curcuma longa (CL) has potential antioxidant effects and may improve hyperglycemia in uncontrolled T1DM/TD1, as well as prevent its complications (higher costs for the maintenance of health per patient, functional disability, cardiovascular disease, and metabolic damage). In addition to the use of compounds to attenuate the effects triggered by diabetes, physical exercise is also essential for glycemic control and the maintenance of skeletal muscles. Our objective is to evaluate the effects of CL supplementation associated with moderate- to high-intensity resistance training on the parameters of body weight recovery, glycemic control, reactive species markers, and tissue damage in rats with T1DM/TD1. METHODS: Forty male 3-month-old Wistar rats (200-250 g) with alloxan-induced T1DM were divided into 4 groups (n = 7-10): sedentary diabetics (DC); diabetic rats that underwent a 4-week resistance training protocol (TD); CL-supplemented diabetic rats (200 mg/kg body weight, 3x a week) (SD); and supplemented diabetic rats under the same conditions as above and submitted to training (TSD). Body weight, blood glucose, and the following biochemical markers were analyzed: lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, creatine kinase (CK), lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS). RESULTS: Compared to the DC group, the TD group showed body weight gain (↑7.99%, p = 0.0153) and attenuated glycemia (↓23.14%, p = 0.0008) and total cholesterol (↓31.72%, p ≤ 0.0041) associated with diminished reactive species markers in pancreatic (↓45.53%, p < 0.0001) and cardiac tissues (↓51.85%, p < 0.0001). In addition, compared to DC, TSD promoted body weight recovery (↑15.44%, p ≤ 0.0001); attenuated glycemia (↓42.40%, p ≤ 0.0001), triglycerides (↓39.96%, p ≤ 0.001), and total cholesterol (↓28.61%, p ≤ 0.05); and attenuated the reactive species markers in the serum (↓26.92%, p ≤ 0.01), pancreas (↓46.22%, p ≤ 0.0001), cardiac (↓55.33%, p ≤ 0.001), and skeletal muscle (↓42.27%, p ≤ 0.001) tissues caused by T1DM. CONCLUSION: Resistance training associated (and/or not) with the use of Curcuma longa attenuated weight loss, the hypoglycemic and hypolipidemic effects, reactive species markers, and T1DM-induced tissue injury.

Effects of passion fruit peel flour (Passiflora edulis f. flavicarpa O. Deg.) in cafeteria diet-induced metabolic disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora edulis f. flavicarpa O. Deg. is a native Brazilian fruit known as sour or yellow passion fruit. From its peel, mainly in the northeast of Brazil, is produced a flour that is largely used as folk medicine to treat diabetes and other metabolic conditions. AIM OF THE STUDY: The aim of the study was to show the effects of P. edulis peel flour (PEPF) in metabolic disorders caused by cafeteria diet in mice. MATERIAL AND METHODS: The antioxidant activity in vitro of PEPF extract was determined by ferric reducing/antioxidant power, ß-carotene/linoleic acid system and nitric oxide scavenging activity assay. C57BL/6 mice divided in 3 groups: Control group, fed on a standard diet (AIN); Cafeteria diet (CAF) group, fed on a cafeteria diet, and PEPF group, fed on a cafeteria diet containing 15% of PEPF, during 16 weeks. The glucose tolerance and insulin sensitivity were evaluated through the glucose tolerance test (GTT) and the insulin tolerance test (ITT). After the intervention period, blood, hepatic, pancreatic and adipose tissues were collected for biochemical and histological analysis. Cholesterol, triglyceride, interleukins and antioxidant enzymes were measured in the liver tissue. RESULTS: PEPF extract presented antioxidant activity in the higher concentrations in the performed assays. The PEPF intake decreased the body weight gain, fat deposition, predominantly in the liver, improved the glucose tolerance and insulin sensitivity in metabolic changes caused by cafeteria diet. CONCLUSION: Together, the data herein obtained points out that P. edulis peel flour supplementation in metabolic syndrome condition induced by CAF-diet, prevents insulin and glucose resistance, hepatic steatosis and adiposity.

Punicic acid was metabolised and incorporated in the form of conjugated linoleic acid in different rat tissues.

The objective of this study was to evaluate the effects of a supplementation of pomegranate seed oil (PSO), being rich in punicic acid, on the biochemical parameters of healthy rats. PSO was given to the animals intragastrically for 40 days at concentrations of 1%, 2% and 4%. There were no changes in their total body weight gain, their serum biochemical markers, or in the oxidative stress in their tissues. However, the TBARS values were reduced in the brains of the animals, noting that no significant amounts of conjugated fatty acids were found in this tissue. Conjugated linoleic acid (CLA) was present in all the other tissues studied. The results obtained have demonstrated that punicic acid from PSO was metabolised and incorporated in the form of CLA in different rat tissues. It did not cause alterations in their lipid metabolism, nor did it participate in the processes of oxidation inhibition.

Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models.

BACKGROUND: Flavonoids are naturally occurring compounds, extensively distributed in plants. T helper (Th)1 and Th2 cytokines balance plays an essential role in the reaction of inflammatory, allergic and infectious processes and transplantation rejection. PURPOSE: This systematic review focuses on various classes of flavonoids with a view to evaluate whether Th1/Th2 cytokine-mediated pathways of immunoenhancement could reduce immune overwhelming reactions. METHODS: Articles in English published from inception to December 2017 reporting flavonoids with immunomodulatory activity for the management of immune-mediated disorders were acquired from PubMed, EMBASE, Scopus and Web of Science and a animal experiments where Th1 and Th2 cytokines were investigated to assess the outcome of immunoregulatory therapy were included. CHAPTERS: 1809 publications were identified and 26 were included in this review. Ten articles described the effect of flavonoids on allergic inflammation in an animal model of asthma; eleven in vivo studies evaluated the immunomodulating and immunosuppressive effects of flavonoids on Th1/Th2 cytokines production and five reports described the regulatory role of flavonoids for Th1/Th2 cytokine responses to experimental arthritis and myocarditis. Modulation of Th1/Th2 cytokine balance, inhibition of eosinophil accumulation and remodeling of the airways and lungs, downregulation of Notch and PI3K signaling pathways, regulation of CD4 + /CD8 + lymphocytes ratio and decreasing inflammatory mediator expressions levels are among the most important immunopharmacological mechanisms for the retrieved flavonoids. CONCLUSION: Naturally occurring flavonoids discussed in the present article have optimal immunomodulation to prevent immune-mediated disorders through management of Th1/Th2 cytokine balance.

Optimization of the antioxidant polyphenolic compounds extraction of yellow passion fruit seeds (Passiflora edulis Sims) by response surface methodology.

The conditions for the solid-liquid extraction of the antioxidant polyphenol compounds from yellow passion fruit seeds were optimized by response surface methodology with the following variables as the extraction parameters: extraction time (12.8-147.2 min), ethanol concentration (13-97%), and temperature (16.4-83.6 °C). The polyphenol content and antioxidant capacity, which were assessed by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, oxygen radical absorbance capacity, ß-carotene bleaching assay, and ferric reducing antioxidant power assay, were considered dependent variables. The association of the dependent variables was effective for explaining the effect of the independent variables within a determination coefficient (R2) range of 0.88-0.96. A moderate-to-strong correlation for the polyphenol content and antioxidant capacity by the investigated methods was established, and optimized conditions were employed to maximize this response. Extraction was carried out at 80 °C using 70% ethanol concentration for 30 min, which was the most efficient condition to obtain an extract with high concentrations of polyphenolic compounds (3.12 g gallic acid equivalent/100 g seed dry basis) and a strong antioxidant capacity. The stilbene piceatannol was the major compound identified by liquid chromatography-electrospray ionization-tandem mass spectrometry (3.68 g/100 g seed dry basis). These results reinforce that agro-industrial waste demonstrates potential as a source of bioactive compounds, with implications in human health as well as in food and chemical industries.

The ethanol extract of Leonurus sibiricus L. induces antioxidant, antinociceptive and topical anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus sibiricus L. (Lamiaceae), popularly known as motherwort, or "erva-de-macaé" or "rubim" in Brazil, is a plant used for the treatment of inflammatory conditions, but few studies have evaluated this anti-inflammatory activity or other activities that may be relevant. AIM OF THE STUDY: This study was undertaken to investigate the antioxidant, antinociceptive and topical anti-inflammatory effects of the ethanol extract of L. sibiricus (EELs). MATERIALS AND METHODS: Chromatographic analysis, determination of total phenolic and flavonoid contents and in vitro antioxidant assays were performed, while the formalin test and ear inflammation induced by 12-0-tetradecanoylphorbol-13-acetate (TPA) were performed in mice. RESULTS: We observed that total phenolic and flavonoids content in EELs were respectively 60.1mg of gallic acid equivalent/g of extract and 15.4mg of catechin equivalent/g of extract. Chlorogenic, caffeic, p-coumaric and ferulic acids, as well as quercetin were identified in EELs. This extract also led to the consumption of the radicals 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and nitric oxide, increased the ferric reducing/antioxidant power (FRAP) and inhibited the spontaneous or FeSO4-induced in vitro lipid peroxidation. In the formalin test, oral pretreatment with EELs (400mg/kg) reduced (p<0.001) the licking/biting time in the second phase, but not in the first phase. In the ear inflammation induced by TPA, the concomitant topical administration of EELs (0.3-3mg/ear) significantly reduced the edema, myeloperoxidase activity, levels of tumoral necrosis factor-α and interleukin-1ß and lipoperoxidation, as well as increased FRAP in ear tissue when compared to vehicle-treated ears. CONCLUSIONS: These results indicate that EELs has antioxidant, antinociceptive and topical anti-inflammatory activities, supporting the use of this plant in folk medicine.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Incorporation and effects of punicic acid on muscle and adipose tissues of rats.

BACKGROUND: This study evaluated the effect of pomegranate seed oil (PSO) supplementation, rich in punicic acid (55 %/C18:3-9c,11 t,13c/CLNA), on the lipid profile and on the biochemical and oxidative parameters in the gastrocnemius muscle and adipose tissues of healthy rats. Linseed oil (LO), rich in linolenic acid (52 %/C18:3-9c12c15c/LNA) was used for comparison. METHODS: Male Wistar rats (n = 56) were distributed in seven groups: control (water); LNA 1 %, 2 % and 4 % (treated with LO); CLNA 1 %, 2 % and 4 % (treated with PSO), po for 40 days. The percentages were compared to the daily feed intake. Fatty acid profile were performed by gas chromatography, antioxidant enzymes activity by spectrophotometer and the adipocytes were isolated by collagenase tissue digestion. Analysis of variance (ANOVA) was applied to check for differences between the groups (control, LNAs and CLNAs) and principal component analysis (PCA) was used to project the groups in the factor-place (PC1 vs PC2) based on the biochemical responses assessed in the study. RESULTS: The fatty acids profile of tissues showed that the LNA percentages were higher in the animals that were fed LO. However, PA was only detected in the adipose tissues. Conjugated linoleic acid (CLA) was present in all the tissues of the animals supplemented with PSO, in a dose dependent manner, and 9c11t-CLA was the predominant isomer. Nevertheless there were no changes in the total weight gain of the animals, the weights of the tissues, and the oxidative stress parameters in the muscle. In addition, there was an increase in the size of the epididymal fat cells in the groups treated with PSO. Principal component analysis (PCA) showed that the CLNAs groups were arranged separately with a cumulative variance of 68.47 %. CONCLUSIONS: The results show that PSO can be used as a source of CLAs but that it does not cause changes in body modulation and does not interfere in the antioxidant activity of healthy rats.

Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer.

Chlorogenic acid (CGA) is found in many foods, including coffee, berries, potatoes, carrots, wine, apples, and various herbs, and has anti-inflammatory, antidiabetic, and antitumoral actions. The CGA is well absorbed orally, and its effects on gastric ulcer have not been previously reported. The present manuscript evaluated the effect of oral administration of CGA on ethanol/HCl (Et/HCl) or nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer model in male Swiss mice. Animals were pretreated with 0.2 % carboxymethylcellulose (vehicle, p.o.), omeprazole (positive control, 30 mg/kg, p.o.), carbenoxolone (antioxidant positive control, 100 mg/kg, p.o.), or CGA (5, 25, or 50 mg/kg, p.o.). One hour later, the gastric ulcer was induced by injecting Et/HCl solution (100 µL/10 g body weight; Et 60 % + HCl 0.03 M) or piroxicam (100 mg/kg, p.o). After another hour or 4 h later, gastric tissues were collected from Et/HCl or piroxicam-treated animals, respectively, to evaluate the size of the lesion, histological alterations, secretion of gastric acid, neutrophil migration, oxidative/antioxidative enzymes, markers of lipid peroxidation, or concentrations of inflammatory mediators. CGA treatment had a gastroprotective effect in both models, reducing the percentage of lesioned area. CGA treatment did not alter the secretion of gastric action but inhibited neutrophil migration and restored the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione, and thiobarbituric acid reactive substances in mice treated with Et/HCl. Additionally, CGA treatment blocked the increase of tumor necrosis factor alpha and leukotriene B4 but did not restore the reduced prostaglandin levels in the NSAID-induced ulcer. Together, the data presented herein show that CGA may be a suitable natural compound for the prevention and treatment of gastric lesions caused by a different etiology.

In vivo and in vitro antioxidant activity and hepatoprotective properties of polyphenols from Halimeda opuntia (Linnaeus) Lamouroux.

Antioxidant activity and hepatoprotective properties of the aqueous extract and tetrahydrofuran-extracted phenolic fractions of Halimeda opuntia (Linnaeus) Lamouroux were investigated in rats with chemically induced liver injury. Total polyphenols were determined by using the Folin-Ciocalteau reagent. Liver damage was induced by CCl(4) and assessed by a histological technique. Reverse transcription/polymerase chain reaction (RT/PCR) analysis showed increased superoxide dismutase (SOD) and catalase (CAT) gene expression and activities in the group treated with free phenolic acid (FPA) fractions of H. opuntia, suggesting inducing effects on both enzymes. In addition, rats treated with FPA fractions displayed lower liver thiobarbituric acid reactive substance (TBARS) levels than those observed for rats in the CCl(4)-treated group. These data suggest that the phenolic fractions from H. opuntia may protect the liver against oxidative stress-inducing effects of chemicals by modulating its antioxidant enzymes and oxidative status.