The inhibitory activity of cocoa phenolic extract against pro-inflammatory mediators secretion induced by lipopolysaccharide in RAW 264.7 cells

Cocoa is a rich source of polyphenols that has been traditionally used as the treatment of several types of inflammation related disease. The response to inflammation comprises the consecutive release of mediators and the enlistment of circulating leukocytes, such as macrophages. Currently, Cocoa-derived polyphenolics have shown anti-inflammatory effects in vivo, but the therapeutic benefits in vitro remain unclear. Therefore, in this study, the effect of cocoa polyphenolic extract (CPE) on RAW 264.7 macrophage cells sensitized by lipopolysaccharide as in vitro inflammatory model was investigated. The anti-inflammatory activity of CPE was assessed by measuring its ability to inhibit the pro-inflammatory enzyme 5-lipoxygenase (5-LOX) and the pro-inflammatory mediators prostaglandin E2 (PGE2), reactive oxygen species (ROS), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). The results show that CPE significantly inhibits 5-LOX activity (p < 0.01). In addition, CPE dose-dependently suppressed the production of PGE2, ROS, NO and TNF-α in RAW 264.7 cells. These data suggest that CPE may be used for the treatment of inflammation and it’s related-diseases

Impaired of a non-DNA dependent methylation status decides the fat decision of bone marrow-derived C3H10T1/2 stem cell

A decrease in the lineage commitment of multipotent Mesenchymal stem cells (MSC) to the bone forming osteoblast lineage and an increase in the commitment to the fat forming adipocyte lineage is more common in bone marrow of elderly persons. A link between methylation status and MSC differentiation remains unclear. Therefore, we hypothesize that hypomethylation may decide the fate decisions of MSC. In the current study, murine bone marrow derived-C3H10T1/2 stem cell was used to examine the role of methylation mechanism on the differentiation potential of stem cells into osteoblasts or adipocytes. C3H10T1/2 cells were treated with Periodate oxidized adenosine (Adox), an inhibitor of S-adenosylhomocysteine-dependent hydrolase (SAHH), which in turn block the non-DNA methylation pathway. The effect of hypomethylation on C3H10T1/2 stem cell differentiation was determined by measuring the alkaline phosphates activity and the degree of mineralization as well as Oil-red O staining and lipid content. The ratio of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) was determined as a metabolic indicator of cellular methylation potential. It was clearly observed that hypomethylation significantly (P < 0.05) reduces SAM: SAH ratio, alkaline phosphates activity, calcification and thereby, osteoblast differentiation. Conversely, adipocyte differentiation was stimulated by hypomethylation. Altogether, our data suggest that non-DNA hypomethylation changes the differentiation potential of C3H10T1/2 stem cells for less osteogenic and more adipogenic

Secondary metabolites, antioxidant, and antiproliferative activities of Dioscorea bulbifera Leaf Collected from Endau Rompin, Johor, Malaysia

Breast cancer is among the most commonly diagnosed cancer and the leading cause of cancer-related death among women globally. Malaysia is a country that is rich in medicinal plant species. Hence, this research aims to explore the secondary metabolites, antioxidant, and antiproliferative activities of Dioscorea bulbifera leaf collected from Endau Rompin, Johor, Malaysia. Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assays, while the cytotoxicity of D. bulbifera on MDA-MB-231 and MCF-7 breast cancer cell lines was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle analysis and apoptosis were assessed using flow cytometry analysis. Phytochemical profiling was conducted using gas chromatography-mass spectrometry (GC-MS). Results showed that methanol extract had the highest antioxidant activity in DPPH, FRAP, and ABTS assays, followed by ethyl acetate and hexane extracts. D. bulbifera tested against MDA-MB-231 and MCF-7 cell lines showed a pronounced cytotoxic effect with IC50 values of 8.96 μg/mL, 6.88 μg/mL, and 3.27 μg/mL in MCF-7 and 14.29 μg/mL, 11.86 μg/mL, and 7.23 μg/mL in MDA-MB-231, respectively. Cell cycle analysis also indicated that D. bulbifera prompted apoptosis at various stages, and a significant decrease in viable cells was detected within 24 h and substantially improved after 48 h and 72 h of treatment. Phytochemical profiling of methanol extract revealed the presence of 39 metabolites such as acetic acid, n-hexadecanoic acid, acetin, hexadecanoate, 7-tetradecenal, phytol, octadecanoic acid, cholesterol, palmitic acid, and linolenate. Hence, these findings concluded that D. bulbifera extract has promising anticancer and natural antioxidant agents. However, further study is needed to isolate the bioactive compounds and validate the effectiveness of this extract in the In in vivo model

La eficacia de metformina y exenatida en pacientes con síndrome de ovario poliquístico (SOP)

Introduction: Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that affects 5-10% of women who are their reproductive age. This meta-analysis aims to evaluate the efficacy of metformin and exenatide, respectively, and to compare the efficacy of both drugs using Body Mass Index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and testosterone level.&nbsp; Method: Scopus, Science Direct, Oxford Journal, Wiley Online Library, and Medline (through the PubMed search engine) were used in this study. Statistical analysis of the included studies was done using the RevMan 5.4 software.&nbsp; Results: There were 6 studies included in the analysis of the study. There was a significant reduction in BMI of PCOS patients with exenatide versus metformin (mean difference = 0.51; 95% confidence interval (CI)= 0.07, 0.96, I 2= 52%; p=0.02). There was also a significant reduction in the testosterone level of PCOS patients with exenatide versus metformin (mean difference = 0.15; 95% confidence interval (CI)= 0.07, 0.22, I 2= 0%; p=0.0002). There was no effect on the mean of LDL-C and of HDL-C when compared between metformin and exenatide This meta-analysis shows that exenatide is effective in reducing BMI and testosterone levels in PCOS patients.&nbsp; Conclusions: There were a significant reduction in BMI and testosterone levels of PCOS patients when exenatide was used as compared to metformin. However, there was no effect on the mean of the LDL-C and HDL-C levels of the PCOS patients.&nbsp;Introducción: El Síndrome del Ovario Poliquístico (SOP) es un trastorno hormonal que afecta al 5-10% de las mujeres que se encuentran en edad reproductiva. este metanálisis tiene como objetivo evaluar la eficacia de la metformina y la exenatida, respectivamente, y comparar la eficacia de ambos fármacos utilizando el Índice de Masa Corporal (IMC), el colesterol de lipoproteínas de baja densidad (LDL-C), el colesterol de lipoproteínas de alta densidad (HDL-C) y los niveles de testosterona. Método: En este estudio se consultaron Scopus, Science Direct, Oxford Journal, Wiley Online Library y Medline a través del motor de búsqueda PubMed. El análisis estadístico de los estudios incluidos se realizó mediante el software RevMan 5.4.&nbsp; Resultados: Hubo 6 estudios incluidos en el análisis del estudio. Hubo una reducción significativa en el IMC de las pacientes con SOP con exenatida frente a metformina (diferencia de medias = 0,51; intervalo de confianza (IC) del 95 % = 0,07; 0,96; I 2 = 52 %; p = 0,02). También hubo una reducción significativa en el nivel de testosterona de los pacientes con SOP con exenatida frente a metformina (diferencia de medias = 0,15; intervalo de confianza (IC) del 95 % = 0,07; 0,22;I 2 = 0 %; p = 0,0002). No hubo efecto sobre la media de LDL-C y de HDL-C cuando se comparó entre metformina y exenatida. Este muestra que la exenatida es eficaz para reducir el IMC y los niveles de testosterona en pacientes con SOP.&nbsp; Conclusiones: Hubo una reducción significativa en el IMC y los niveles de testosterona de los pacientes con SOP cuando se usó exenatida en comparación con metformina. Sin embargo, no hubo efecto sobre la media de los niveles de LDL-C y HDL-C de las pacientes con SOP

Dimethyl sulfoxide and their toxicity

The aim of the present mini-review was to report a toxic effect of dimethyl sulfoxide (DMSO) that has indicated to change the histology of the liver and kidney of rats. DMSO is a powerful co-solvent and often is used in early metabolic studies when compounds are poorly characterized and difficult to become soluble in water. To become soluble, they have to be dissolved in organic lipophilic solvents (vehicles). Following its conventional use, plant extract has been exposed to various intense and sub-acute toxicity studies to legitimize its toxicological security. Normally, DMSO has low fundamental toxicity yet plant extract when dissolved in 10% DSMO can cause noteworthy confined toxic impacts in the liver and kidney of rats. Be that as it may, vehicles currently in use have pleiotropic impacts, which are regularly obscure. Therefore, researchers ought to be cautious in the preparation and storage of substances before they are dispensed to animals. If this is not done, it may lead to accidental adverse effects on the animals and frequently result in inaccurate outcomes. In this mini-review, we summed up data on biological impacts of the DMSO most generally utilized lipophilic medication vehicles. Other than in experimental models, the information, where accessible, are presented on the impacts of solvents in therapeutic use in rodents. All in all, a few suggestions are given on the utilization of medication solvents in tests

Comments on “Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics”

A finite strain constitutive model to predict a complex elastoplastic deformation behaviour involves very high pressures and shockwaves in orthotropic materials is developed in this work. The important feature of the proposed hyperelastic-plastic constitutive model is a Mandel stress tensor combined with the new generalised orthotropic pressure. The formulation is developed in the isoclinic configuration and allows for a unique treatment for elastic and plastic orthotropy. The elastic orthotropy is taken into account through a stress tensor decomposition combined with the new pressure. A yield surface of Hill’s yield criterion aligned uniquely within the principal stress space is adopted to characterise plastic orthotropy by means of the evolving structural tensors. An isotropic hardening is adopted to define the evolution of plastic orthotropy. The formulation is further combined with a shock equation of state (EOS) and Grady spall failure model to predict shockwave propagation and spall failure in the materials, respectively. The proposed constitutive model is implemented as a new material model in the Lawrence Livermore National Laboratory (LLNL)-DYNA3D code of UTHM’s version. The ability of the newly constitutive model to describe finite strain deformation and shock propagation in orthotropic materials is first investigated against plate impact data of aluminium alloy in the longitudinal and transverse directions before a comparison against plate impact test data of carbon fibre reinforced epoxy composites along the through-thickness direction is finally conducted. A good agreement is obtained in each test

Induction of chronic subclinical systemic inflammation in sprague–dawley rats stimulated by intermittent bolus injection of lipopolysaccharide

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague–Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation

Stingless bee honey protects against lipopolysaccharide induced-chronic subclinical systemic inflammation and oxidative stress by modulating Nrf2, NF-κB and p38 MAPK

Background: Epidemiological and experimental studies have extensively indicated that chronic subclinical systemic inflammation (CSSI) and oxidative stress are risk factors for several chronic diseases, including cancer, arthritis, type 2 diabetes, and cardiovascular and neurodegenerative diseases. This study examined the protective effect of stingless bee honey (SBH) supplementation against lipopolysaccharide (LPS)-induced CSSI, pointing to the possible involvement of NF-κB, p38 MAPK and Nrf2 signaling. Methods: CSSI was induced in male Sprague Dawley rats by intraperitoneal injection of LPS three times per week for 28 days, and SBH (4.6 and 9.3 g/kg/day) was supplemented for 30 days. Results: LPS-induced rats showed significant leukocytosis, and elevated serum levels of CRP, TNF-α, IL-1β, IL-6, IL-8, MCP-1, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), accompanied with diminished antioxidants. Treatment with SBH significantly ameliorated inflammatory markers, MDA and 8-OHdG, and enhanced antioxidants in LPS-induced rats. In addition, SBH decreased NF-κB p65 and p38 MAPK, and increased Nrf2 expression in the liver, kidney, heart and lung of LPS-induced rats. Furthermore, SBH prevented LPS-induced histological and functional alterations in the liver, kidney, heart and lung of rats. Conclusion: SBH has a substantial protective role against LPS-induced CSSI in rats mediated via amelioration of inflammation, oxidative stress and NF-κB, p38 MAPK and Nrf2 signaling

Anti-inflammatory and anti-oxidative properties of cocoa ethanolic extract rich in polyphenols

This study aimed to investigate the anti-oxidative and anti-inflammatory properties of ethanolic cocoa extract-rich in polyphenols in vitro. It is hypothesized that cocoa extract polyphenols may be benefit for diseases-related to chronic inflammation. The accumulation of macrophage, during the inflammatory state, plays a potent role in releasing pro-inflammatory markers. Additionally, the accumulation of free radicals along with inflammatory state is considered to be the initiative of several diseases such as cancer, atherosclerosis, diabetes and arthritis. Finding a potent agent suppressing the free radicals and pro-inflammatory markers is still required. Polyphenols have been thought to own strong anti-oxidative and anti-inflammatory characteristics. To confirm this assumption, the phenolic compounds of cocoa bean powder were isolated and identified by column chromatography and HPLC. Polyphenolic compounds were then characterized by HPLC-UV-/ESI-MS-MS. Five phenolic compounds were detected namely, catechine, epicatechine, gallic acid,cholorgenic acid and protocatechuic acid. In this study, the scavenging or the TAC (%) (Total Antioxidant Capacity) of cocoa polyphenol (CP) extract that contain 114.0 mg/g of gallic acid –equivalent phenolics and 94.3 mg/g catechin- equivalent flavonoids were also investigated. Their free radical-scavenging activity was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, β-carotene bleaching test,and XO (Xanthin Oxidase) inhibitory activity and compared with standard drugs (allopurinol) in different concentrations (5, 10, 20) mg/ml. TAC was further assessed by CP extract against the myoglobin-induced oxidation of ABTS (2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) and expressed as Trolox equivalent in different concentration (100, 200, 300) μM/TE g. CP extract had significantly (P < 0.05) potential antioxidant activities with various concentrations. On the other hand, the anti-inflammatory activity of CP extract was assessed with their ability to inhibit the pro-inflammatory enzyme 5-lipooxygenase (5-LOX) using synthetic substrate (Soybean lipoxygenase) and mediators prostaglandin E2 (PGE2), Reactive Oxygen Species (ROS), Nitric Oxide (NO) and Tumor necrosis factor-alpha (TNF-α) using RAW264.7 cells sensitized by lipopolysaccharide (LPS). Our findings indicated that cocoa extract significantly produced inhibition against 5-LOX activity (P< 0.05). In addition, CP extract, in a dose-dependent manner, exhibited a high ability in suppressing the production of ROS, NO, TNF-α, and PGE2 in RAW 264.7 cells. Conclusively, our in vitro study suggest that the improvement of anti-oxidative and inflammatory state is a pivotal action of dietary polyphenols-derived from cocoa beans which in turn provide a rationale application in clinical nutrition practice for treatment of chronic diseases

Ameliorative activities of Malaysian stingless bee honey on lipopolysaccharide-induced inflammation and oxidative stress In vivo and its underlying mechanisms

Inflammation and oxidative stress have been considered the major contributor in developing chronic diseases including cancer, atherosclerosis, diabetes, neurodegenerative diseases, arthritis and obesity. A number of dietary and nutraceuticals interventions to attenuate inflammation- and oxidative stress-related diseases target pro-inflammatory mediators, reactive oxygen species, transcription factors including nuclear factor-kappa B (NF-κB), and nuclear factor erythroid 2- releated factor 2 (Nrf-2) and specific regulatory transcription proteins including P38- mitogen activated protein kinases (P38-MAPK) and high mobility group box-1 protein (HMGB-1) and. Stingless bee honey (SBH) has been recently found to be rich in bioactive compounds especially, polyphenols more than honey-made by normal bee. The unique body size of stingless bee helps her stretch itself inside a plenty number of flowers which increase the diversity of collected polyphenols and preserve them from degradation. In this study, SBH had a higher phenolic content than other types of normal honey and there were fifteen phenolic compounds identified using LCMS/ MS. The richness of SBH in phenolic compounds were also manifested with high and significant total antioxidant capacity measured by DPPH, ABTS and ORAC assays. The significant statistical correlation between polyphenols content and antioxidant results confirmed the biological actions of SBH against free radicals. Subsequently, a model of chronic subclinical systemic inflammation was developed by injecting male rats with 1 mg/kg of lipopolysaccharide thrice per week for 28 days. The results demonstrated an elevation in C-reactive protein, IL-6, TNF-α and lymphocyte along with inflammatory changes in the histological features of heart, lung, kidney and liver tissues. Then, the ability of SBH to mitigate inflammation and oxidative stress was studied in two separate experiments; systemic acute inflammation and chronic subclinical systemic inflammation. In the first experiment, SBH was supplemented at two different doses (4.6 and 9.3 g/kg/day) for seven days prior to induce systemic acute inflammation by injecting male rat with 5 mg/kg LPS. In the second experiment, SBH was supplemented for 30 days at two different doses (4.6 and 9.3 g/kg/day) concurrently with 1 mg/kg of LPS injection thrice per week for 28 days to induce chronic subclinical systemic inflammation. In both experiments, SBH demonstrated a significant reduction in pro-inflammatory mediators and oxidative stress. Regulating the protein levels of NF-κB, p38-MAPK, HMGB-1 and activating Nrf-2 in SBH treated group unveiled partially the mechanism of SBH against inflammation and oxidative stress. The histopathological examination of both studies revealed that SBH exceled a reduction in the pathology of heart, lung, kidney and liver. These biological activates of SBH could be due to the synergistic actions of polyphenols and it also provides a novel insight into the possible mechanism behind the preventive actions of SBH on the emergence of inflammation and oxidative markers in rats with LPS-induced inflammation. Collectively, the results presented in this thesis suggest that SBH can mitigate and prevent systemic acute inflammation and chronic subclinical systemic inflammation along with oxidative stress via regulating NF-κB, P38-MAPK, HMGB-1 and Nrf-2. SBH is expected to be a useful natural supplement for alleviating and preventing oxidative stress and chronic inflammationrelated diseases