Dietary Polyphenolic Compounds Research Articles

Heterologous expression and enzymatic characteristics of sulfatase from Lactobacillus plantarum dy-1.

Barley, rich in bioactive components including dietary fiber, polyphenolic compounds and functional proteins, exhibits health benefits such as regulating glucose and lipid metabolism. Previous studies have found that the content and composition of free phenolic acids in barley may be significantly changed by fermentation with the laboratory patented strain Lactobacillus plantarum dy-1 (L. p dy-1), but the mechanism of enzymatic release of phenolic acid remains to be elucidated. Based on this, this study aimed to identify the key enzyme in L. p dy-1 responsible for releasing the bound phenolic acid and to further analyze its enzymatic properties. The Carbohydrate-Active enZYmes database revealed that L. p dy-1 encodes 7 types of auxiliary enzymes, among which we have identified a membrane sulfatase. The enzyme gene LPMS05445 was heterologous to that expressed in E. coli, and a recombinant strain was induced to produce the target protein and purified. The molecular weight of the purified enzyme was about 59.9 kDa, with 578.21 U mg-1 enzyme activity. The optimal temperature and pH for LPMS05445 expression were 40 °C and 7.0, respectively. Furthermore, enzymatic hydrolysis by LPMS05445 can obviously change the surface microstructure of dietary fiber from barley bran and enhance the release of bound phenolic acid, thereby increasing the free phenolic acid content and improving its physiological function. In conclusion, sulfatase produced by Lactobacillus plantarum dy-1 plays a key role in releasing bound phenolic acids during the fermentation of barley.

Chlorogenic acid enhances PPARγ-mediated lipogenesis through preventing Lipin 1 nuclear translocation in Staphylococcus aureus-exposed bovine mammary epithelial cells

Chlorogenic acid (CGA) as one of the most ubiquitously dietary polyphenolic compounds, has been reported to have various antimicrobial effects and exhibit strong anti-inflammatory ability. Staphylococcus aureus is a gram-positive bacterium that can induce mastitis. However, the mechanism through which S. aureus infection affects lipid synthesis and whether CGA have protective effect on S. aureus reduced lipid synthesis is not fully understood. In this study, the internalization of S. aureus reduced intracellular lipid droplet formation, decreased the levels of intracellular triacylglycerol, total cholesterol and 7 types of fatty acid and downregulated the expression of lipogenic genes FAS, ACC, and DGAT1 in bovine mammary epithelial cells (BMECs). In addition, we found that S. aureus intracellular infection attenuated mTORC1 activation resulting in Lipin 1 nuclear localization. Remarkablely, S. aureus infection-mediated repression of lipid synthesis related to the mTORC1 signaling and Lipin 1 nuclear localization can be alleviated by CGA. Thus, our findings provide a novel mechanism by which lipid synthesis is regulated under S. aureus infection and the protective effects of CGA on lipid synthesis in BMECs.

An Overview on Phytoestrogen based antihypertensive agent for their potential Pharmacological Mechanism

Recent studies shown that the data of clinical, experimental and epidemiological studies indicates that dietary phytoestrogens, flavonoids and polyphenolic compounds have shown most potent activities for prevention in CVDs. The major class of compounds found in phytoestrogen. These phytoestrogens are sub-classified into coumestans, prenylflavonoids and isoflavones. These class having the most active class in estrogenic effects, polyphenols (also known as polyhydroxyphenols includes tannic acid, ellagitannin. These studies also indicate that dietary supplements and food nutrients have profound cardioprotective effects in the primary as well as secondary coronary heart disease and hence they are considered as cardiovascular friendly natural products. The mechanism of cardioprotection produced by dietary nutritional supplements such as phytoestrogens (soy and soy protein), flavonoids (citrus fruits, pulses, red wine, tea and cocoa), olive oil, omega-3 fatty acids (fish oil and fish-based products), lycopene (tomato and tomato-based products), resveratrol (grapes and red wine), coffee, and soy in the prevention and treatment of cardiovascular disorders have been discussed in the following review (in parenthesis) with the emphasis of epidemiological and clinical studies. Based on the intriguing results of various studies, prophylactic and therapeutic potential of cardiovascular friendly natural products have been suggested.

Risk Assessment of Chlorogenic and Isochlorogenic Acids in Coffee By-Products.

Chlorogenic and isochlorogenic acids are naturally occurring antioxidant dietary polyphenolic compounds found in high concentrations in plants, fruits, vegetables, coffee, and coffee by-products. The objective of this review was to assess the potential health risks associated with the oral consumption of coffee by-products containing chlorogenic and isochlorogenic acids, considering both acute and chronic exposure. An electronic literature search was conducted, revealing that 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-DCQA) are the major chlorogenic acids found in coffee by-products. Toxicological, pharmacokinetic, and clinical data from animal and human studies were available for the assessment, which indicated no significant evidence of toxic or adverse effects following acute oral exposure. The current state of knowledge suggests that long-term exposure to chlorogenic and isochlorogenic acids by daily consumption does not appear to pose a risk to human health when observed at doses within the normal range of dietary exposure. As a result, the intake of CQAs from coffee by-products can be considered reasonably safe.

Natural products and Hypertension: Scope and role in Antihypertensive Therapy

Recent studies shown that the data of clinical, experimental and epidemiological studies indicates that dietary phytoestrogens, flavonoids and polyphenolic compounds have shown most potent activities for prevention in CVDs. The major class of compounds found in phytoestrogen. These phytoestrogens are sub-classified into coumestans, prenylflavonoids and isoflavones. These class having the most active class in estrogenic effects, polyphenols (also known as polyhydroxyphenols includes tannic acid, ellagitannin. These studies also indicate that dietary supplements and food nutrients have profound cardioprotective effects in the primary as well as secondary coronary heart disease and hence they are considered as cardiovascular friendly natural products. The mechanism of cardioprotection produced by dietary nutritional supplements such as phytoestrogens (soy and soy protein), flavonoids (citrus fruits, pulses, red wine, tea and cocoa), olive oil, omega-3 fatty acids (fish oil and fish-based products), lycopene (tomato and tomato-based products), resveratrol (grapes and red wine), coffee, and soy in the prevention and treatment of cardiovascular disorders have been discussed in the following review (in parenthesis) with the emphasis of epidemiological and clinical studies. Based on the intriguing results of various studies, prophylactic and therapeutic potential of cardiovascular friendly natural products have been suggested.

Response-Surface-Methodology-Based Optimization of High-Quality Salvia hispanica L. Seed Oil Extraction: A Pilot Study

Chia seeds play an important role in human health and nutrition since they contain dietary fiber, lipids, protein, polyphenolic compounds, and polyunsaturated fatty acids. The present study aimed to evaluate the yield and quality of chia seed oil (extracted using the screw press method) in terms of total phenolic content, acid, and peroxide levels. A central composite design was used to optimize the extraction procedure, and the response surface methodology was used to assess the results. The restriction die size of 1 cm, pressing temperature of 53 °C, and no dry heat were the optimal conditions for extracting the desired quality of chia seed oil according to the predicted response surface methodology model. The conditions were evaluated and a 29.47% yield was achieved, with a TPC of 2.20 µg GAE/g of oil, acid content of 0.96 mg KOH/g of oil, and peroxide content of 2.87 mEq/Kg of oil. The extraction process exceeded 45.10 min. Antioxidant activities of 19.21 μg TE/g of oil (ABTS radical scavenging activity), 5.69 μg TE/g of oil (DPPH radical scavenging activity), and 186.68 μg CE/g of oil (nitric oxide free radical scavenging activity) were observed. The fatty acid composition of the chia seed oil samples is also reported herein. We report the optimal conditions for extracting oil from local cultivar chia seeds, thus helping to analyze changes in the composition and impact due to geographical differences in oil quality. The extracted chia seed oil could be utilized for functional foods, cosmetics, and pharmaceutical applications.

The effect of curcumin on the cadmium-induced mitochondrial apoptosis pathway by metallothionein 2A regulation

Cadmium (Cd) is one of the most toxic heavy metals used in various industries, including metal plating, batteries and plastics and environmental pollutant. Cd in the environment is a detrimental factor that cannot be biodegraded and accumulates in human organs. The skin is the first target organ after Cd topical exposure. Curcumin is a natural dietary polyphenolic compound with many beneficial effects, including antioxidant, anti-inflammatory and anticancer activities. However, the effect of curcumin against Cd-induced toxicity in human keratinocytes has not been reported. In this study, we investigated the effects of curcumin against Cd-induced apoptosis in keratinocytes and the underlying molecular mechanisms. Cd resulted in apoptosis as shown by Annexin V/7-AAD double staining. Cd promoted the cleavage of poly (ADP ribose) polymerase-1 (PARP-1) and caspase 3 and suppressed Bcl-2. In addition, Cd induced the release of cytochrome c and Smac from the mitochondria into the cytosol, which is an intrinsic apoptosis-specific process. Curcumin inhibited the early and late apoptosis caused by Cd. The changes in apoptotic markers induced by Cd were significantly reversed by curcumin. Next, we evaluated the effect of curcumin on metallothionein (MT), a cysteine-rich protein that plays a key role in metal detoxification. Curcumin increased the level of MT2A mRNA and the expression of MT2. Interestingly, the antiapoptotic effects of curcumin were reversed under the knockdown of MT2A, suggesting that MT2A is a critical target of curcumin. These findings indicate the potential of curcumin as a novel compound for protection against Cd-mediated skin damage by MT2A modulation.

Ellagic acid ameliorates hexavalent chromium-induced renal toxicity by attenuating oxidative stress, suppressing TNF-α and protecting mitochondria

Nephrotoxicity is an important adverse effect of oxidative stress induced by hexavalent chromium [Cr(VI)]. The effect of ellagic acid, a dietary polyphenolic compound with potent antioxidant activity, was investigated in Cr(VI)-induced kidney injury. Six groups of male Wistar rats were treated intragastrically with vehicle or ellagic acid (15 and 30 mg/kg) for 10 days. On day 10, rats received saline or Cr(VI) (K2Cr2O7 15 mg/kg) subcutaneously. Cr(VI) significantly increased kidney weight, affected kidney function assessed by biomarkers in blood and urine (protein, creatinine and urea nitrogen), caused histological changes (tubular injury and glomerular capillary tuft damage), increased markers of oxidative stress and reduced the activity of antioxidant enzymes. In addition, Cr(VI) altered mitochondrial ultrastructure, impaired mitochondrial respiration, increased lipid peroxidation, and inhibited the function of mitochondrial enzymes. Pretreatment with ellagic acid (30 mg/kg) attenuated all the aforementioned alterations. Furthermore, we explored whether ellagic acid might regulate the tumor necrosis factor-alpha (TNF-α)/receptor-interacting protein kinase 3 (RIPK3) pathway, reducing Cr(VI)-induced tubular necrosis. Cr(VI) upregulated both TNF-α and RIPK3, but ellagic acid only decreased TNF-α levels, having no effect on RIPK3 content. Therefore, understanding the mechanisms through which Cr(VI) promotes necroptosis is crucial for future studies, in order to design strategies to mitigate kidney damage. In conclusion, ellagic acid attenuated Cr(VI)-induced renal alterations by preventing oxidative stress, supporting enzymatic activities, suppressing TNF-α, and preserving mitochondrial ultrastructure and function, most likely due to its antioxidant properties.

Natural Polyphenols as SERCA Activators: Role in the Endoplasmic Reticulum Stress-Related Diseases.

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a key protein responsible for transporting Ca2+ ions from the cytosol into the lumen of the sarco/endoplasmic reticulum (SR/ER), thus maintaining Ca2+ homeostasis within cells. Accumulating evidence suggests that impaired SERCA function is associated with disruption of intracellular Ca2+ homeostasis and induction of ER stress, leading to different chronic pathological conditions. Therefore, appropriate strategies to control Ca2+ homeostasis via modulation of either SERCA pump activity/expression or relevant signaling pathways may represent a useful approach to combat pathological states associated with ER stress. Natural dietary polyphenolic compounds, such as resveratrol, gingerol, ellagic acid, luteolin, or green tea polyphenols, with a number of health-promoting properties, have been described either to increase SERCA activity/expression directly or to affect Ca2+ signaling pathways. In this review, potential Ca2+-mediated effects of the most studied polyphenols on SERCA pumps or related Ca2+ signaling pathways are summarized, and relevant mechanisms of their action on Ca2+ regulation with respect to various ER stress-related states are depicted. All data were collected using scientific search tools (i.e., Science Direct, PubMed, Scopus, and Google Scholar).

Stimulation of the intestinal microbiota with prebiotics enhances hepatic levels of dietary polyphenolic compounds, lipid metabolism and antioxidant status in healthy rats

How stimulation of the intestinal microbiota may regulate the health-promoting effects of dietary polyphenols on liver function has not been fully elucidated. Therefore, in this study, we examined whether a combination of fructooligosaccharides (FOSs) and a polyphenol preparation (PP) might stimulate the intestinal microbiota to increase liver levels of polyphenol-derived bioactive compounds. We also investigated how this supplementation affected lipid metabolism and antioxidative status in Wistar rats without diet-induced metabolic disturbances. Addition of FOSs to the diet with the PP (CPF group) considerably reduced the caecal activity of microbial enzymes and elevated the production of short-chain fatty acids, mostly propionic acid. The CPF group exhibited increased relative abundances of caecal bacteria that were able to metabolize polyphenols from the examined preparation. Considerably elevated concentrations of ellagic acid, ellagic acid dimethyl ether glucuronide, 4-hydroxybenzoic acid and methyl cyanidin-3-sophoroside were found in the liver in the CPF group. In addition, hepatic downregulation of HIF1α, AHR and SREBP1c, which are molecular factors that regulate lipid metabolism and antioxidative status, was also found in this group. These changes might explain the considerably reduced levels of fat, triglycerides and lipid peroxidation in the liver in the CPF group. Moreover, the combination of FOSs and the PP considerably elevated the total antioxidant status and activity of superoxide dismutase in the blood. To conclude, stimulation of the intestinal microbial composition and activity with FOSs increased the health-promoting effects of the PP by elevating polyphenolic metabolite levels in the liver and improving lipid metabolism and antioxidative status in healthy rats. Therefore, the combination of FOSs and polyphenols might be a valuable dietary supplement that is able to support preventive healthcare.

Protective Effects of Diets Rich in Polyphenols in Cigarette Smoke (CS)-Induced Oxidative Damages and Associated Health Implications.

Cigarette smoking has been responsible for causing many life-threatening diseases such as pulmonary and cardiovascular diseases as well as lung cancer. One of the prominent health implications of cigarette smoking is the oxidative damage of cellular constituents, including proteins, lipids, and DNA. The oxidative damage is caused by reactive oxygen species (ROS, oxidants) present in the aqueous extract of cigarette smoke (CS). In recent years, there has been considerable interest in the potential health benefits of dietary polyphenols as natural antioxidant molecules. Epidemiological studies strongly suggest that long-term consumption of diets (fruits, vegetables, tea, and coffee) rich in polyphenols offer protective effects against the development of cancer, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. For instance, green tea has chemopreventive effects against CI-induced lung cancer. Tea might prevent CS-induced oxidative damages in diseases because tea polyphenols, such as catechin, EGCG, etc., have strong antioxidant properties. Moreover, apple polyphenols, including catechin and quercetin, provide protection against CS-induced acute lung injury such as chronic obstructive pulmonary disease (COPD). In CS-induced health problems, the antioxidant action is often accompanied by the anti-inflammatory effect of polyphenols. In this narrative review, the CS-induced oxidative damages and the associated health implications/pathological conditions (or diseases) and the role of diets rich in polyphenols and/or dietary polyphenolic compounds against various serious/chronic conditions of human health have been delineated.

The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause immunosuppression and cytokine storm, leading to lung damage and death. The clinical efficacy of anti-SARS-CoV-2 drugs in preventing viral entry into host cells and suppressing viral replication remains inadequate. MicroRNAs (miRNAs) are crucial to the immune response to and pathogenesis of coronaviruses, such as SARS-CoV-2. However, the specific roles of miRNAs in the life cycle of SARS-CoV-2 remain unclear. miRNAs can participate in SARS-CoV-2 infection and pathogenesis through at least four possible mechanisms: 1. host cell miRNA expression interfering with SARS-CoV-2 cell entry, 2. SARS-CoV-2-derived RNA transcripts acting as competitive endogenous RNAs (ceRNAs) that may attenuate host cell miRNA expression, 3. host cell miRNA expression modulating SARS-CoV-2 replication, and 4. SARS-CoV-2-encoded miRNAs silencing the expression of host protein-coding genes. SARS-CoV-2-related miRNAs may be used as diagnostic or prognostic biomarkers for predicting outcomes among patients with SARS-CoV-2 infection. Furthermore, accumulating evidence suggests that dietary polyphenolic compounds may protect against SARS-CoV-2 infection by modulating host cell miRNA expression. These findings have major implications for the future diagnosis and treatment of COVID-19.

P-coumaric acid ameliorates fipronil induced liver injury in mice through attenuation of structural changes, oxidative stress and inflammation

Fipronil is a broad-spectrum phenylpyrazole insecticide and has been used effectively in the agriculture. Due to its widespread use and bioaccumulation in the environment, it possesses significant threat to human and animals. P-coumaric acid is a natural dietary polyphenolic compound that has anti-oxidant and anti-inflammatory property. The present study was aim to investigate the ameliorative effect of p-coumaric acid on fipronil induced liver injury. The mice were divided into five groups (SHAM, FPN, FPN/PCA/50, FPN/PCA/100 and PCA/100) and challenged with fipronil @ 25 mg/kg bw (half of LD50). Haematological, liver function biomarkers (ALT, AST, ALP, GGT), biochemical parameters (MPO, oxidative, nitrosative stress and anti-oxidant enzyme activity), levels of serum and liver inflammatory cytokines (TNF-α, IL-1β and IL-10), histopathology were monitored. Fipronil administration caused a significant increase in liver enzymes with concomitant significant increase in inflammatory cytokines (TNF-α, IL-1β, IL-10) and myeloperoxidase activity. A significant increase in oxidative stress (lipid peroxidation, nitric oxide) as well as down regulation of anti-oxidant enzymes like superoxide dismutase (SOD) and catalase (CAT) along with histopathological changes such as microsteatosis, hypertrophy of the hepatocytes and necrosis were observed on fipronil administration. Administration of p-coumaric acid against fipronil caused decreased serum liver enzymes, inflammatory cytokines, myeloperoxidase activity and oxidative stress along with improvement in anti-oxidant enzyme levels and structural changes induced by fipronil. Thus p-coumaric acid ameliorates the FPN induced liver injury in mice through attenuation of structural changes, oxidative stress, and inflammation.

Synergistic Effects of Limosilactobacillus fermentum ASBT-2 with Oxyresveratrol Isolated from Coconut Shell Waste.

Value-added phytochemicals from food by-products and waste materials have gained much interest and among them, dietary polyphenolic compounds with potential biological properties extend a promising sustainable approach. Oxyresveratrol (Oxy), a stilbenoid polyphenol, possesses great therapeutic potential, though its pharmacokinetic issues need attention. A good source of oxyresveratrol was found in underutilized coconut shells and the synbiotic applications of the compound in combination with a potential probiotic isolate Limosilactobacillus fermentum ASBT-2 was investigated. The compound showed lower inhibitory effects on the strain with minimum inhibitory concentration (MIC) of 1000 µg/mL. Oxyresveratrol at sub-MIC concentrations (500 µg/mL and 250 µg/mL) enhanced the probiotic properties without exerting any inhibitory effects on the strain. The combination at sub- MIC concentration of the compound inhibited Salmonella enterica and in silico approaches were employed to elucidate the possible mode of action of oxy on the pathogen. Thus, the combination could target pathogens in the gut without exerting negative impacts on growth of beneficial strains. This approach could be a novel perspective to address the poor pharmacokinetic properties of the compound.

ToxDP2 Database: Toxicity prediction of dietary polyphenols

Polyphenols are bioactive substances that minimize the risk of a variety of chronic diseases. Exposure to polyphenol bioactive compounds in our diet has increased across the globe, with amplified expectations from consumers, industry, and regulators centered on the potential benefits and essential safety of these compounds. Several data resources for beneficial properties of dietary polyphenols are present; however, toxicological information remains partial. We present a dynamic web-based database to assess dietary polyphenols' safety and fulfill the toxicity data gaps in the domain of food safety. The database (ToxDP2) comprises 415 dietary polyphenolic compounds, distributed into 15 subclasses with 25,792 collected and predicted data points. This web server facilitates the exploration of polyphenols for divergent applications. The data-driven approach on the ToxDP2 provides researchers with an understanding of polyphenols structure–function-toxicity relationships beneficial for developing nutraceuticals, pharmaceuticals, herbal supplements, and formulations.

Formulation and quality evaluation of finger millet (Eleusine coracana (L.) gaertn.) flour incorporated biscuits.

Replacing the ingredients used in biscuits with potential nutritive ingredients would be beneficial to improve the nutritional quality of the biscuits. Although, finger millet is highly nutritious when compared to other most commonly consumed cereals, limited availability of processed food products in ready-to-eat form has restricted the finger millet consumption. The present study was focused on formulating biscuits by replacing refined wheat flour with finger millet flour. Four biscuit samples were formulated by replacing different percentages of refined wheat flour with finger millet flour. Physicochemical and microbiological properties of the biscuits were evaluated. Nutritional and antioxidant properties of the biscuit, which was formulated by replacing 50% of refined wheat flour with finger millet flour, were evaluated and compared with a control biscuit which was prepared using refined wheat flour. The finger millet flour incorporated biscuit was nutritionally superior to the control biscuit in terms of dietary fibers and polyphenolic compounds including flavonoids. Besides, replacement of refined wheat flour with finger millet flour in biscuit formulation enhanced the antioxidant properties of the biscuit. Therefore, the finger millet flour incorporated biscuit can be considered as a good source of antioxidants.

Polyphenols Modulating Effects of PD-L1/PD-1 Checkpoint and EMT-Mediated PD-L1 Overexpression in Breast Cancer.

Investigating dietary polyphenolic compounds as antitumor agents are rising due to the growing evidence of the close association between immunity and cancer. Cancer cells elude immune surveillance for enhancing their progression and metastasis utilizing various mechanisms. These mechanisms include the upregulation of programmed death-ligand 1 (PD-L1) expression and Epithelial-to-Mesenchymal Transition (EMT) cell phenotype activation. In addition to its role in stimulating normal embryonic development, EMT has been identified as a critical driver in various aspects of cancer pathology, including carcinogenesis, metastasis, and drug resistance. Furthermore, EMT conversion to another phenotype, Mesenchymal-to-Epithelial Transition (MET), is crucial in developing cancer metastasis. A central mechanism in the upregulation of PD-L1 expression in various cancer types is EMT signaling activation. In breast cancer (BC) cells, the upregulated level of PD-L1 has become a critical target in cancer therapy. Various signal transduction pathways are involved in EMT-mediated PD-L1 checkpoint overexpression. Three main groups are considered potential targets in EMT development; the effectors (E-cadherin and Vimentin), the regulators (Zeb, Twist, and Snail), and the inducers that include members of the transforming growth factor-beta (TGF-β). Meanwhile, the correlation between consuming flavonoid-rich food and the lower risk of cancers has been demonstrated. In BC, polyphenols were found to downregulate PD-L1 expression. This review highlights the effects of polyphenols on the EMT process by inhibiting mesenchymal proteins and upregulating the epithelial phenotype. This multifunctional mechanism could hold promises in the prevention and treating breast cancer.

Investigations of curcumin release from chitosan nanoparticles by ultrasound waves and TPP concentration effects

The major active agent of the turmeric plant, which has extensive pharmacological activities, is curcumin, a dietary polyphenolic compound. As a potential medium for drug delivery, a nanoparticle chitosan polymer has been created. Chitosan is a low-toxic, biodegradable, biocompatible and secure polymer used to produce nanoparticles. Chitosan nanoparticles have been prepared using the process of ionic crosslinking. The mean particle size of chitosan nanoparticles was 180-200 nm in the range and curcumin encapsulation efficiencies were 82%. Ultrasound is a non-invasive means to administer medicines to the darkest areas of the human body. Cumulative release was studied in order to study how ultrasound allows curcumin to be extracted from chitosan nanoparticles. The effect of ultrasound and tripolyphosphate concentration on the release behavior of curcumin from chitosan nanoparticles is discussed in this paper. Using the ultrasound wave, drug release from chitosan nanoparticles was improved.

Polyphenolic Compounds and Gut Microbiome in Cardiovascular Diseases.

The onset of Cardiovascular Disease (CVD) is known to be associated with multiple risk factors related to exogenous exposures on predisposed genetic makeup. Diet and lifestyle have a cascade effect on microbiota biodiversity, thus impacting inflammation and heart health. Atherosclerosis is a type of CVD where chronic inflammation contributes to plaque buildup in the arteries resulting in narrowed blood vessels, which obstruct blood flow. Polyphenolic compounds, including flavonoids, most commonly consumed in the form of plants, have been identified to have various mechanisms of action to reduce the inflammatory response in the body. Flavonoids provide a variety of nutraceutical functions including antioxidant, antimicrobial, anti-inflammatory, antiangiogenic, antitumor, and improved pharmacokinetic properties. Therefore, the medicinal use of polyphenolic compounds as an intervention for the inflammatory response, especially relating to the gut microbiome, may significantly reduce the risk of atherosclerotic plaque development and disease onset. This review addresses the role of polyphenolic compounds and gut microbiome in cardiovascular disease. Research studies conducted in cells and animals were reviewed. These studies clearly illustrate that dietary polyphenolic compounds influence resident gut microbiota thus they are associated with the prevention of atherosclerosis progression. Further research in this field is warranted to identify potential gut microbiome mediated therapeutic approaches for CVD.

Curcumin alleviates arsenic-induced toxicity in PC12cells via modulating autophagy/apoptosis.

Arsenic is a recognized highly toxic contaminant, responsible for numerous human diseases and affecting many millions of people in different parts of the world. Contrarily, curcumin is a natural dietary polyphenolic compound and the main active ingredient in turmeric. Recently it has drawn great attention due to its diverse biological activities, strong antioxidant properties and therapeutic potential against many human ailments. In this study, we aimed to explore the protective effects and the regulatory role of curcumin on arsenic-induced toxicity and gain insights into biomolecular mechanism/s. Arsenic (10μM) treatment in PC12cells for 24h induced cytotoxicity by decreasing cell viability and intracellular glutathione level and increasing lactate dehydrogenase activity and DNA fragmentation. In addition, arsenic caused apoptotic cell death in PC12cells, which were confirmed from flow cytometry results. Moreover, arsenic (10μM) treatment significantly down-regulated the inhibition factors of autophagy/apoptosis; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap protein expressions, up-regulated the enhanced factors of autophagy/apoptosis; ULK, LC3, p53, Bax, cytochrome c, caspase 9, cleaved caspase 3 proteins and eventually caused autophagic and apoptotic cell death. However, curcumin (2.5μM) pretreatment with arsenic (10μM) effectively saves PC12cells against arsenic-induced cytotoxicity through increasing cell viability, intracellular GSH level and boosting the antioxidant defense system, and limiting the LDH activity and DNA damage. Furthermore, pretreatment of curcumin with arsenic expressively alleviated arsenic-induced toxicity and cell death by reversing the expressions of proteins; mTOR, Akt, Nrf2, ERK1, Bcl-x, Xiap, ULK, LC3, p53, Bax, cytochrome c, caspase 9 and cleaved caspase 3. Our findings indicated that curcumin showed antioxidant properties through the Nrf2 antioxidant signaling pathway and alleviates arsenic-triggered toxicity in PC12cells by regulating autophagy/apoptosis.