Certain polyphenol compounds found in fruits and vegetables can inhibit the activation of pattern recognition receptors .Cyanidin-3-glucoside and their metabolites suppress LPS-induced cytokine production in THP-1 monocytes . BB supplementation did not affect postprandial FFA and cytokine concentrations ; however, it attenuated the propensity of monocyte activation induced by elevated concentrations of FFAs in LPL-treated blood ex vivo . Supplementation with 2 and 4 servings of BBs with the breakfast meal resulted in decreased LPL-induced secretion of IL-1b and IL-6, respectively, in postprandial whole blood without affecting concentrations of FFAs released . These results suggest that the consumption of BB powder with the breakfast meal could decrease the propensity of postprandial monocyte activation in the micro-environment where blood monocytes directly interact with endothelial cells that secrete LPL. The inhibitory effect of the BB powder on LPL induced cytokine production is likely due to the inhibitory effects of polyphenols on FFA-induced activation of pattern recognition receptors including TLRs rather than potential off target effects on LPL because BB intake did not alter the concentrations of FFAs released. It was reported that intake of strawberries , orange juice , tomatoes , or blackcurrants with a high-fat meal was cardioprotective by decreasing selective inflammatory markers . Because postprandial FFA concentrations may change in time, the impact of polyphenol-rich BBs on FFA-induced postprandial inflammatory status will need to be studied in the future with blood samples taken at multiple time points, including the period when FFA concentrations rebound close to or exceed fasting concentrations. The study has several limitations. The study was not powered to look at interactions between sex and consumption of BB powder. In addition, the subjects were allowed to return to their normal daily activities after consumption of the test meal until their return for the postprandial blood draw. Because sex differences and physical activity could have affected postprandial responses,square plant pots recruitment strategies to create a balanced sex distribution and control of physical activity may need to be implemented in future studies.

In summary, consumption of an MHF breakfast decreased postprandial plasma FFA and cytokine concentrations compared with those of fasting plasma, suggesting that eating breakfast acutely attenuates the inflammatory status in postprandial blood. Plasma FFA concentrations may be an important determinant modulating monocyte activation as assessed by TLR-mediated IL-1b secretion and the expression of adhesion molecules . These results corroborate the results from our previous mechanistic studies that both palmitic acid and endogenous FFAs can directly activate TLR2 and induce the expression of proin- flammatory cytokines in primary monocytes and whole blood. A corollary of these results is that the concentration of plasma FFAs may be one of the important determinants affecting the inflammatory status in blood. Plasma FFA concentrations are generally elevated in obesity and diabetic patients. Thus, our results lead to the next translational question as to whether plasma FFA concentrations can be a target of dietary or pharmacological intervention to alleviate the increased inflammation in metabolic diseases. Supplementation with BB powder did not affect the postprandial FFA and cytokine concentrations; however, it suppressed FFA-induced cytokine production in LPL-treated blood.Unhealthy diets, e.g. Western style diets high in fats and carbohydrates, can trigger inflammatory conditions that are associated with the development of several pathologies including type 2 diabetes , nonalcoholic fatty liver disease , cardiovascular disease, cancer, and certain neuropathies. Oral intake of bio-actives to counteract inflammation is a strategy with the potential for high impact on human health, especially when these bio-actives are present in diets and dietary components, e.g. fruits and vegetables, in amounts provided by realistic intakes. Following the ingestion of any food, a physiological postprandial response occurs as a result of nutrient absorption and metabolism. However, excess consumption of lipids and/or carbohydrates leads to a series of short-term events described as postprandial dysmetabolism. These events include alterations in glucose and lipid metabolism, endotoxemia, inflammation and oxidative stress.

Importantly, postprandial dysmetabolism has been associated with a higher risk, among other pathologies, for cardiovascular disease and mortality, nonalcoholic fatty liver disease, and T2D progression. It is well documented that even a single meal high in fat and/or carbohydrates can lead to postprandial hyperglycemia, hypertriglyceridemia and/or endotoxemia. High fat diets cause metabolic endotoxemia mainly through intestinal permeabilization and/or co-transport of lipopolysaccharides with chylomicrons. Once in the circulation, endotoxins can reach different cells and organs where they promote, among other effects, the production of proinflammatory molecules, e.g. cytokines and chemokines, leading to systemic inflammation and oxidative stress, which directly affect metabolic pathways. Additionally, postprandial dyslipidemia per se contributes to altered glucose metabolism, insulin resistance and inflammation. Mechanisms involved in inflammation- and oxidative stress-associated insulin resistance include the activation of the redox sensitive kinases, i.e. c-Jun N-terminal kinases and IκB kinase , and of transcription factor NF-κB downstream of IKK. The activation of both, JNK and IKK, as well as the upregulation of the NF-κB-regulated protein tyrosine phosphatase 1B, inhibit the insulin signaling pathway resulting in tissue insulin resistance. As a counterbalance to the aforementioned proinflammatory consequences of high fat diets, the consumption of select fruits and vegetables could prevent and/or attenuate these unhealthy conditions. Evidence for the latter is complex when considering overall intakes, types of fruits and vegetables consumed, and other variables associated with population-based studies. On the other hand, a large body of evidence from experimental animal models suggests consistent benefits of select phytochemicals against the development of obesity and associated pathologies mainly triggered by consumption of high fructose and/or high fat diets. Among those phytochemicals, anthocyanidins are being actively investigated for their potential to mitigate unhealthy conditions, particularly metabolic disorders. In this regard, mounting evidence supports a potential beneficial action of AC consumption on T2D and cardiovascular disease. Furthermore, consumption of AC-rich foods has been inversely correlated with overall mortality. Chemically, AC are aglycones of anthocyanins, which are the flavonoids that provide color to grapes, dark berries , purple/black corn, and black rice, among other fruits and vegetables. According to the number and position of functional groups around the flavonoid scaffold, AC are sub-classified into cyanidins, delphinidins, malvidins, petunidins, peonidins and pelargonidins. These differences in substitutions have been shown to have a major impact on their mechanisms of action. In this regard, we recently reported that cyanidin and delphinidin were more effective than malvidin, petunidin and peonidin at mitigating inflammation, e.g. preventing tumor necrosis factor alpha -induced activation of transcription factor NF-κB in an intestinal cell model.

Understanding the mechanisms by which AC modify cellular functions is crucial to define public health recommendations in terms of diets, i.e. foods and potential supplementation. Regulation of inflammation and oxidative stress are central mechanisms involved in the capacity of cyanidin- and delphinidin-rich extracts to mitigate the deleterious gastrointestinal and metabolic effects of chronic high fat dietary consumption in mice. In terms of redox regulation, it is unfeasible that AC could act as direct antioxidants given their poor intestinal absorption that results in low tissue concentrations. However, AC and/or AC metabolites can act regulating redox homeostasis, e.g. modulating NADPH oxidase expression, oxidative stress and inflammation. Importantly, cyanidin and delphinidin have been shown to prevent high fat diet-induced endotoxemia in mice by regulating intestinal permeability through redox-dependent and independent mechanisms. This study investigated the beneficial effects of supplementation in healthy individuals with a cyanidin- and delphinidin-rich extract , firstly, on parameters of inflammation, i.e. endotoxemia, and secondly,plastic pots for planting on parameters of lipid and glucose metabolism and redox signaling. These parameters were associated with changes in redox homeostasis and signaling. Volunteers consumed a 1026-kcal high-fat meal simultaneously with either the CDRE, or a placebo in a randomly assigned, double blind, placebo-controlled crossover intervention. The CDRE mitigated HFM-induced acute endotoxemia and several parameters of postprandial dysmetabolism associated with the consumption of the HFM. The study was a randomly assigned, double blind, placebo-controlled crossover intervention comparing the effects of supplementation with CDRE or placebo. Each intervention lasted 5 h after consumption of the HFM and supplements, separated by a washout period of 7–30 d between visits. The study was conducted at the Ragle Facility at the University of California, Davis in accordance with the Declaration of Helsinki guidelines. All procedures were approved by UCD IRB administration and UCD Social & Behavioral Committee. Written informed consent was obtained from the study volunteers. Clinical interventions were conducted between December 2017 and March 2018. Recruitment and screening followed the Consolidated Standards of Reporting Trials strategy . Briefly, female and male volunteers that showed interest in the study were provided with information about the design and the procedures. If willing to commit to the study, a screening phone interview was conducted to assess their potential eligibility. Those who showed interest and met the basics of the inclusion and exclusion criteria were called for an in-person visit . Participants were asked to attend in a fasted state . The written informed consent was explained, and upon approval, anthropometric parameters were recorded and a finger-prick blood sample was obtained to determine glucose and triglycerides using a CardioCheck analyzer . Participants that met inclusion criteria were invited to be part of the clinical study and to schedule two in-person visits separated by a washout period of: i) at least 7 d to prevent significant carryover effects based on the fact that AC and their metabolites tend to disappear from circulation within 48 h of intake; ii) less than 30 d, to prevent major changes in lifestyle, especially those associated to periods of food over consumption and seasonal influences.

The day of visit 0, participants were provided with dietary restriction and guideline instructions asking them to: i) not consume phenolrich foods for 24 h before each of the study visits; ii) consume a similar low-fat dinner the evening before each meal ; and iii) complete a 3-d food record before visits 1 and 2 to assess compliance with the dietary requirements. The days of the study visits, upon arrival glucose and triglyceride levels were assessed in blood samples collected by finger prick using the CardioCheck analyzer to confirm that participants were in a fasted state and their adherence to the inclusion/exclusion criteria. Body weight and blood pressure were also determined. Participants were then asked to consume the placebo or CDRE following the randomization scheme. Powders were packaged in sealed black sachets, which were coded to blind the study personnel to the treatment. Study personnel dissolved the powder in 200 mL of water, which was provided to each participant along with the prepared HFM. The participants were asked to drink the CDRE supplement drink and then eat the HFM within 15 min. The HFM consisted of English muffin bread, sausage, egg and cheese, obtained from the US market with carotenoid-free palm oil added to bring the total dietary fat to the desired level. The total energy content of the HFM was 1026 Kcal with 70.5 g of fat , 270 mg cholesterol, 70.2 g carbohydrate, and 33 g protein with a total of 62% of the energy originated from fat, 25% from carbohydrates, and 13% from protein. Venous blood was taken at time 0 and 0.5, 1, 2, 3, and 5 h after consumption of the HFM, and collected in three separated tubes for plasma, serum and peripheral blood mononuclear cells isolation. The primary end-point of the present study was to assess whether or not the CDRE could attenuate postprandial endotoxemia induced by consumption of a HFM. Postprandial endotoxemia was evaluated using two biomarkers, plasma LPS and LBP. For LPS, there was a significant effect for time where consumption of the HFM triggered increased plasma LPS levels in both groups. The treatment effect confirmed that plasma LPS concentrations were lower in the CDRE group compared to the placebo group. The time-by-treatment interaction was not significant . The total AUC was calculated in order to evaluate the extent of exposure to LPS in each group over the 5- h postprandial time period. AUC values were 44% lower when participants received CDRE compared to when they received placebo with the HFM . Plasma LBP showed a significant treatment effect , wherein average LBP concentrations were lower in the CDRE group compared to the placebo group. Time and time-by-treatment interaction were non-significant. Consistent with plasma LPS, and the observed treatment effect, a significant effect of CDRE was observed for the LBP AUC . Thus, the CDRE treatment elicited a smaller LBP AUC response over the 5-h postprandial time period compared to the placebo .