Modulation of the Gut Microbiota by the Plantaricin-Producing Lactiplantibacillus plantarum D13, Analysed in the DSS-Induced Colitis Mouse Model.

Lactiplantibacillus plantarum D13 shows antistaphylococcal and antilisterial activity, probably due to the synthesis of a presumptive bacteriocin with antibiofilm capacity released in the cell-free supernatant (CFS), whose inhibitory effect is enhanced by cocultivation with susceptible strains. An in silico analysis of the genome of strain D13 confirmed the pln gene cluster. Genes associated with plantaricin biosynthesis, structure, transport, antimicrobial activity, and immunity of strain D13 were identified. Furthermore, the predicted homology-based 3D structures of the cyclic conformation of PlnE, PlnF, PlnJ, and PlnK revealed that PlnE and PlnK contain two helices, while PlnF and PlnJ contain one and two helices, respectively. The potential of the strain to modulate the intestinal microbiota in healthy or dextran sulphate sodium (DSS)-induced colitis mouse models was also investigated. Strain D13 decreased the disease activity index (DAI) and altered the gut microbiota of mice with DSS-induced colitis by increasing the ratio of beneficial microbial species (Allobaculum, Barnesiella) and decreasing those associated with inflammatory bowel disease (Candidatus Saccharimonas). This suggests that strain D13 helps to restore the gut microbiota after DSS-induced colitis, indicating its potential for further investigation as a probiotic strain for the prevention and treatment of colitis.

Combined effects of valproate and naringin on kidney antioxidative markers and serum parameters of kidney function in C57BL6 mice.

Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and dehydration. The aim of this in vivo study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.

The Effect of a High-Protein Diet Supplemented with Blackthorn Flower Extract on Polyphenol Bioavailability and Antioxidant Status in the Organs of C57BL/6 Mice.

The health benefits of polyphenols are based on their bioavailability, which is why a significant portion of research focuses on factors that affect their bioavailability. Previous studies suggest that the intake of polyphenols along with macronutrients in food represents one of the key factors influencing the bioavailability of polyphenols and, consequently, their biological activity in the organism. Since polyphenols in the human diet are mainly consumed in food together with macronutrients, this study investigated the in vivo absorption, metabolism, and distribution of polyphenolic compounds from the water extract of blackthorn flower (Prunus spinosa L.) in combination with a protein-enriched diet in the organs (small intestine, liver, kidney) of C57BL/6 mice. The bioaccumulation of polyphenol molecules, biologically available maximum concentrations of individual groups of polyphenol molecules, and their effect on the oxidative/antioxidative status of organs were also examined. The results of this study indicate increased bioabsorption and bioavailability of flavan-3-ols (EC, EGCG) and reduced absorption kinetics of certain polyphenols from the groups of flavonols, flavones, and phenolic acids in the organs of C57BL/6 mice after intragastric administration of the water extract of blackthorn flower (Prunus spinosa L.) in combination with a diet enriched with whey proteins. Furthermore, subchronic intake of polyphenols from the water extract of blackthorn flower (Prunus spinosa L.) in combination with a diet enriched with whey proteins induces the synthesis of total glutathione (tGSH) in the liver and superoxide dismutase (SOD) in the liver and small intestine. The results of this study suggest potential applications in the development of functional foods aimed at achieving the optimal health status of the organism and the possibility of reducing the risk of oxidative stress-related disease.

The Role of Hyperthermia in Potentiation of Anti-Angiogenic Effect of Cisplatin and Resveratrol in Mice Bearing Solid Form of Ehrlich Ascites Tumour.

The aim of this study was to investigate the therapeutic potential of resveratrol in combination with cisplatin on the inhibition of tumour angiogenesis, growth, and macrophage polarization in mice bearing the solid form of an Ehrlich ascites tumour (EAT) that were exposed to whole-body hyperthermia treatment. In addition, we investigated whether a multimodal approach with hyperthermia and resveratrol could abolish cisplatin resistance in tumour cells through the modulation of histone deacetylase (HDAC) activity and levels of heat shock proteins (HSP70/HSP90) and contribute to the direct toxicity of cisplatin on tumour cells. The tumour was induced by injecting 1 × 106 EAT cells subcutaneously (sc) into the thighs of Balb/c mice. The mice were treated with resveratrol per os for five consecutive days beginning on day 2 after tumour injection and/or by injecting cisplatin intraperitoneally (ip) at a dose of 2.5 mg/kg on days 10 and 12 and at a dose of 5 mg/kg on day 15. Immediately thereafter, the mice were exposed to systemic hyperthermia for 15 min at a temperature of 41 °C. The obtained results showed that the administration of resveratrol did not significantly contribute to the antitumour effect of cisplatin and hyperthermia, but it partially contributed to the immunomodulatory effect and to the reduction of cisplatin toxicity and to a slight increase in animal survival. This treatment schedule did not affect microvessel density, but it inhibited tumour growth and modulated macrophage polarization to the M1 phenotype. Furthermore, it abolished the resistance of tumour cells to cisplatin by modulating HDAC activity and the concentration of HSP70 and HSP90 chaperones, contributing to the increased lifespan of mice. However, the precise mechanism of the interaction between resveratrol, cisplatin, and hyperthermia needs to be investigated further.

The Effects of Nettle Extract Consumption on Liver PPARs, SIRT1, ACOX1 and Blood Lipid Levels in Male and Female C57Bl6 Mice.

The aim of this study was to evaluate how nettle (Urtica dioica L.) water extract consumption would interact with regulators of peroxysomal lipid oxidation, histone deacetylase, and markers of oxidative stress in the liver and blood lipid levels in male and female C57Bl6 mice. Metabolically unchallenged (healthy) mice (n = 5 per sex) were treated with a nettle extract in a dose of 40 mg of total polyphenols in the extract per kg mice body weight. The nettle extract was applied daily along with normal diet for 15 days. The serum triglycerides, cholesterol, HDL, LDL, and liver PPAR-α, PPAR-γ, PGC-1-α, ACOX1, SIRT1, MDA, SOD, CAT, and GSH were compared between exposed and unexposed (control) animals. In males, the PPAR-α, PGC1-α, and ACOX1 levels together with systemic HDL cholesterol were significantly (p ≤ 0.05) increased while the LDL cholesterol decreased (p ≤ 0.05). In females, no changes in PPAR-α and PGC1-α or serum lipids were noted, but the ACOX1 content in the liver was significantly (p ≤ 0.05) increased. The SIRT1 activity increased (p ≤ 0.05) only in females. In both sexes, the PPAR-γ levels were not significantly (p ≤ 0.05) affected in either sex. The results indicate that nettle plant extract has the potential to modulate selected transcriptional factors and histone deacetylase in vivo, with certain sex differences, which should be studied further in similar models.

Antioxidant and Anti-Atherogenic Activities of Essential Oils from Myrtus communis L. and Laurus nobilis L. in Rat.

Essential oils (EOs) from aromatic and medicinal plants, such as myrtle (Myrtus communis L.) and Laurel (Laurus nobilis L.), are gaining popularity as a potential ingredient in functional foods and nutraceuticals. This study aims to investigate whether the essential oils (EOs) could be effective in weight control, antioxidative and antilipidemic status of rats by affecting microbiota and its enzymes activity and whether changes in intestinal enzyme activity affect the health of rats. The intragastric application of laurel and myrtle EOs to rats for two weeks affects weight loss, reduces glycolytic activity, lipid parameters (cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C)) and atherogenic indicators, leading to cardiovascular protection. Laurel EO can be an excellent candidate for the treatment of drug-induced obesity and related diseases, since it affects lipid metabolism in the liver and inhibits the enzymes responsible for the metabolism of carbohydrates into glucose in the digestive tract, leading to weight loss. In contrast, myrtle EO shows a better antioxidant capacity in most tissues, except kidneys, where it causes a pro-oxidative effect, compared to laurel EO. Myrtle EO increases the permeability and instability of the erythrocyte membrane, resulting in a loss of selectivity for the entry of toxic substances into the cell. On the other hand, myrtle EO leads to intestinal inflammation by reducing the number of probiotic bacteria and increasing Enterobacter.

Association of chronic inflammation with cardiovascular risk in chronic obstructive pulmonary disease-A cross-sectional study.

Background and Aims: COPD is progressive lung disease with known higher cardiovascular (CV) risk, mainly attributed to smoking of cigarettes as the main etiological factor of disease. The aim of this study was to compare CV risk in patients with COPD to control groups of smokers and non-COPD and to investigate the relation of lung function variables, COPD severity, and smoking with Systemic Coronary Risk Estimation (SCORE) risk calculation, arterial stiffness (AS) values, and biological systemic inflammatory markers. Methods: A total of 208 subjects were included in this study: 61 subjects diagnosed with COPD, 83 smokers without COPD, and 64 nonsmokers without COPD. Medical history and clinical data were recorded, including assessment of pulmonary function and AS, calculation of ankle-brachial index, blood analysis, and CV risk assessment by SCORE risk calculation. Results: Subjects with COPD had significantly higher values of SCORE calculation of risk, central aortic pressure, AS, and markers of systemic inflammation compared to control groups of smokers and nonsmokers without COPD (p < 0.001). Furthermore, statistically significant increase in hs-CRP concentration was found between the COPD group and the control group of non-COPD smokers (p < 0.001), and a statistically significantly higher SCORE calculation was found in the COPD group compared to control groups of smokers and nonsmokers without COPD (p < 0.001). Conclusion: The results of the research support further identification and research of biological markers and simple specific tests such as arteriography that will enable progress in personalized treatment of patients with COPD and better primary and secondary prevention of comorbidities with the aim of improved treatment outcome.

Effects of Volatile Anaesthetics and Iron Dextran on Chronic Inflammation and Antioxidant Defense System in Rats.

Iron, as an essential microelement, is involved in cell proliferation, metabolism, and differentiation. It also modulates the fate and function of macrophages in hematopoiesis and macrophage-mediated inflammatory responses. On the other hand, anesthetics can affect the inflammatory process by modulating the response to stress or the functions of immune cells. The aim of this paper is to understand how excessive iron intake alters physiological, functional characteristics of peripheral tissues and whether different anesthetics can alter cell metabolism regarding oxidative stress (OS) and inflammation through regulation of macrophage polarization. Y59 rats were injected intraperitoneally with iron dextran solution at a dose of 50 mg/kg or were exposed to inhaled anesthetics sevoflurane and isoflurane and their combination for 28 days every other day. The results show that the use of anesthetics reduces the rat's organ weight and increases OS in peripheral tissues, leading to M1 macrophage polarization. Excessive iron intake leads to increased OS, inflammation, and an increased ratio of IL-12/IL-10 cytokines to the M1 macrophage phenotype. Iron, in combination with sevoflurane, has a protective effect in tissues showing the M2 phenotype of macrophages. The combination of iron dextran and isoflurane in rats leads to an increase in the erythropoiesis process made possible through the induction of hypoxia.

Antioxidative and Anti-Inflammatory Activities of Chrysin and Naringenin in a Drug-Induced Bone Loss Model in Rats.

Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1ß, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP.

Beneficial Effects of Laurel (Laurus nobilis L.) and Myrtle (Myrtus communis L.) Extract on Rat Health.

Polyphenols of Laurel and Myrtle exhibit structural diversity, which affects bioavailability, metabolism, and bioactivity. The gut microbiota plays a key role in modulating the production, bioavailability and, thus the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. The aim of this study was to investigate whether the polyphenolic components of Laurel and Myrtle aqueous extract have beneficial effects on rat health. The growth of lactic acid bacteria (LAB), ß-glucuronidase, ß-glucosidase, ß-galactosidase activity, pH value, body weight change and food efficacy ratio after intragastric treatment of rats with Laurel and Myrtle extract at doses of 50 and 100 mg/kg for two weeks were investigated. The endogenous populations of colonic probiotic bacteria (Lactobacilli and Bifidobacteria) were counted on selective media. According to the obtained data, Laurel extract in the applied dose of 50 and 100 and Myrtle extract (100 mg/kg) positively affects the rats health by increasing the number of colonies of Lactobacilli and Bifidobacteria compared to the control group, causes changes in glycolytic enzymatic activity and minor change in antioxidative tissue activity. In addition, high doses of Laurel increase food efficiency ratio, while Myrtle has the same effect at a lower dose.

Resveratrol and its nanocrystals: A promising approach for cancer therapy?

There has been a significant research interest in nanocrystals as a promising technology for improving the therapeutic efficacy of poorly water-soluble drugs, such as resveratrol. Little is known about the interaction of nanocrystals with biological tissue. The aim of this study was to investigate the potential use of resveratrol (RSV) and its nanocrystals (NANO-RSV) as antitumor agents in Ehrlich ascites tumour (EAT)-bearing mice and the interaction of nanocrystals with biological tissue through biochemical and histological changes of kidney, liver and EAT cells. After intraperitoneal injection of 2.5 × 106 cells into the abdominal cavity of mice, treatment of animals was started next day by injecting RSV or NANO-RSV at a dose of either 25 or 50 mg/kg every other day for 14 days. The results show that the administration of resveratrol and its nanocrystals lead to significant reductions in the proliferation of tumour cells in the abdominal cavity, and a reduction of the number of blood vessels in the peritoneum, with low systemic toxicity. In histopathological examinations, greater hepatocellular necrosis and apoptosis, hepatic fibrosis around the central vein and degeneration with minor fatty change were observed with RSV than with NANO-RSV. Inflammation with proximal tubular necrosis and renal glomerulus swelling were also observed, together with slight elevation of several biochemical parameters in both the RSV and NANO-RSV groups. In order to increase the beneficial effects and reduce risks associated with resveratrol nanocrystals, additional factors such as dose, genetic factors, health status, and the nature of the target cells should also be considered.

Oxidative Stability, Microbial Safety, and Sensory Properties of Flaxseed (Linum usitatissimum L.) Oil Infused with Spices and Herbs.

In our study, we assessed whether the addition of basil, fennel, oregano, rosemary, and chili can improve oxidative stability and sensory properties of flaxseed oil (FO) during 180 days of storage or induce oil contamination by microorganisms. Results showed that addition of spices and herbs in FO affected the hydrolytic changes, but far less than 2% of free fatty acids after storage, which was in line with regulations. Further, the addition of spices and herbs in FO decreased peroxide value (even up to 68.7% in FO with oregano) vs. FO whose value increased during storage, indicating increased oxidative stability and prolongation of shelf life of infused oils. The antioxidant activity of the infused oils ranged from 56.40% to 97.66%. In addition, the phenol content was higher in all infused oils (6.81-22.92 mg/kg) vs. FO (5.44 mg/kg), indicating that herbs and spices could scavenge free radicals and inhibit lipid peroxidation, while sensory analysts showed that FO infused with chili had the lowest bitterness intensity. According to the presence of certain microorganisms, results highlighted the need to develop new methods for inactivating microorganisms that would not only provide a microbial safety, but also preserve the beneficial properties of the oils/products.

Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse.

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg-1). Two days later, CA (50 mg kg-1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.

Natural Phenolic Acid, Product of the Honey Bee, for the Control of Oxidative Stress, Peritoneal Angiogenesis, and Tumor Growth in Mice.

Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 106) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity.

The effect of high-fat diet and 13-cis retinoic acid application on lipid profile, glycemic response and oxidative stress in female Lewis rats.

Vitamin A and its metabolites are key regulators of the development of adipose tissue and associated metabolic complications. The aim of this study was to determine the effect of high fat diet and 13-cis retinoic acid (13 cRA) application on metabolic parameters, adipogenic and inflammatory indicators in female Lewis rats. Female rats of Lewis strain were fed standard laboratory diet (STD) and high fat diet (HFD, 45% of saturated fatty acids) during 30 days. The groups were divided into additional 3 groups (6 rats each): two experimental groups that received 13 cRA orally on a daily basis during 30 days (7.5 mg/kg and 15 mg/kg, respectively) and the control group that was given sunflower oil. Animals were sacrificed after 60 days. Feeding of Lewis rats with chronic HFD diet with 13 cRA supplementation increased weight gain, adiposity index, dyslipidaemia, hyperleptinaemia, insulin resistance, VLDL concentrations, oxidative stress and atherogenic indices. Administration of 13 cRA in Lewis rats fed STD did not change the weight of the animals, but it slightly increased the atherogenic parameters. 13 cRA and HFD affect metabolic parameters, glucose and lipid metabolism in Lewis rats and its administration has a completely different effect on metabolism in rats fed STD, highlighting the complex role of vitamin A supplementation in obesity. Other factors, such as genetics, age, sex, adipose tissue distribution, also must be taken into consideration.

Interactions between Cisplatin and Quercetin at Physiological and Hyperthermic Conditions on Cancer Cells In Vitro and In Vivo.

Quercetin (QU), a hyperthermic sensitizer, when combined with cisplatin (CP) affects tumor growth. To determine the effects of QU and CP and their interactions, multimodal treatment in vitro and in vivo models under physiological and hyperthermic conditions was performed. In vitro, different sensitivity of T24 and UMUC human bladder cancer cells was observed after short-term exposure to QU (2 h) and CP (1 h). Effects of both compounds were investigated at low and high micromolar concentrations (1 and 50 µM, respectively) under both thermal conditions. QU acted in additive or synergistic manner in combination with CP between physiological condition and hyperthermia. As determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, short-term application of QU and CP reduced cell viability. Clonal assay also indicated that combined treatment with QU and CP is lethal to bladder cancer cells in both conditions. In vivo, CP (5 or 10 mg kg-1) and QU (50 mg kg-1) acted synergistically with hyperthermia (43 °C) and inhibited tumor growth, activated immune effectors and increased mice survival. Our results demonstrate that combined treatment with CP and QU may increase death of tumor cells in physiological and hyperthermic conditions which could be clinically relevant in locoregional chemotherapy.

Effect of Propolis on Diet-Induced Hyperlipidemia and Atherogenic Indices in Mice.

Obesity, a major health problem worldwide, is associated with increased cardiovascular risk factors, such as dyslipidemia, glucose intolerance, and hypertension. We investigated the antioxidative capacity of the ethanol extract of propolis (EEP) and its effect on the lipid profile, the hepatorenal function, and the atherogenic indices in mice fed with a high-fat diet (HFD). EEP (50 mg/kg) was given orally to mice for 30 days. After the treatments, levels of the serum total triglyceride and cholesterol, the high density lipoprotein (HDL-c) and low density lipoprotein (LDL-c) cholesterols, the serum enzymes, and the metabolites were measured, and atherogenic indices [atherogenic index of plasma (AIP); cardiac risk ratio (CRR); cardioprotective index (CPI); atherogenic coefficient (AC)] were calculated and compared with the antioxidant, the reducing power, the radical-scavenging, and the chelating activity of EEP. The HFD diet with EEP significantly reduced the negative lipid profile and lowered AIP, CRR, and AC and increased CPI in animals on a HFD. In addition, EEP reduced the weight of mice and lipid accumulation in the liver, and it had significant in vitro antioxidative activities. The EEP possesses anti-hyperlipidemic and antioxidant activity and exhibits protective action on the cardiovascular system and hepatorenal functions. Our results contribute towards the validation of the traditional use of propolis as a food supplement in aiding hyperlipidemic disorders.

The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of Bone Turnover in Rats.

Nutrition is an important factor that influences bone metabolism, the endocrine and/or paracrine system, and bone-active mineral elements homeostasis. We studied antiosteoporotic effects of grape seed proanthocyanidins extract, icariin or alendronate (ALN) in retinoic acid-induced (13cRA) bone loss in rats. Proanthocyanidins and icariin have beneficial effects on bone health; they have improved the bone weight reduction, the length and the diameter of the bone, calcium, and phosphorus content in bone ash, bone mineral density (BMD), the biochemical markers of bone turnover and uterus atrophy induced by 13cRA. All results suggest that proanthocyanidins and icariin reverse osteoporosis in 13cRA rats by stimulating bone formation or regulating bone resorption by their antioxidative and estrogenic-like activity without toxic side-effects observed in ALN treatment.