Raspberry protective role in inflammatory diseases: An overview

Background: Raspberry leaf (RL; Rubus idaeus) is a by-product of raspberry cultivation and has been proposed to be a rich source of micronutrients and potential bioactive components, including polyphenols. However, the precise chemical composition of the non-nutrient (poly)phenols in RL has not been as extensively studied. Objective: To evaluate the (poly)phenolic content of six RL samples from different geographical locations and to explore the impact of brewing duration on the levels of phenolic compounds available for absorption following consumption. Methods: A total of 52 polyphenolic constituents were investigated in the RL samples using Liquid Chromatography–Mass Spectrometry (LC-MS), and RL tea samples were analysed for ellagitannins, flavonoids, and phenolic acids. Tea samples were extracted using 80:20 (v/v) methanol/acidified water (0.1% formic acid) to maximise polyphenol recovery, with two sonication steps (30 and 25 min), followed by centrifugation, filtration, and storage at −18 °C. Extractions were performed in triplicate for comprehensive profiling. Additionally, raspberry leaf tea (2 g) was brewed in 200 mL of boiling water at various times (0.5–20 min) to simulate standard consumption practices; this was also performed in triplicate. This approach aimed to quantify polyphenols in the brew and identify optimal steeping times for maximum polyphenol release. Results: Raspberry leaf (RL) samples from six geographical sources were analysed, with 37 compounds identified in methanol and 37 in water out of the 52 targeted compounds, with only 7 compounds not detected in either methanol or water extracts. The analysis indicated that the total measured polyphenol content across the six samples from various sources ranged between 358.66 and 601.65 mg/100 g (p < 0.001). Ellagitannins were identified as the predominant polyphenolic compound in all RL samples, ranging from 155.27 to 394.22 mg/100 g. The phenolic acid and flavonoid concentrations in these samples exhibited a relatively narrow range, with the phenolic acids spanning from 38.87 to 119.03 mg/100 g and the flavonoids ranging from 125.03 to 156.73 mg/100 g. When brewing the tea, the 5 min extraction time was observed to yield the highest level of polyphenols (505.65 mg/100 g) (p< 0.001), which was significantly higher than that with shorter (409.84 mg/100g) and longer extraction times (429.28 mg/100 g). Notably, ellagic acid levels were highest at 5 min (380.29 mg/100 g), while phenolic acid peaked at 15 min (50.96 mg/100 g). The flavonoid content was shown to be highest at 4 min (82.58 mg/100 g). Conclusions: RL contains a relatively high level of polyphenols, particularly ellagic acid; thus, its consumption may contribute to the daily intake of these health-beneficial non-nutrient components.

Raspberries, derived from different cultivar varieties, are a popular ingredient of everyday diet, and their biological activity is a point of interest for researchers. The ethanol-water extracts from four varieties of red (Rubus idaeus'Ljulin', 'Veten', 'Poranna Rosa') and black (Rubus occidentalis'Litacz') raspberries were evaluated in the range of their antimicrobial properties as well as phenolic content - sanguiin H-6, free ellagic acid and anthocyanins. The antimicrobial assay was performed with the use of fifteen strains of bacteria, both Gram-negative and Gram-positive. The antimicrobial activity of the extracts varied and depended on the analysed strain of bacteria and cultivar variety, with the exception of Helicobacter pylori, towards which the extracts displayed the same growth inhibiting activity. Two human pathogens Corynebacterium diphtheriae and Moraxella catarrhalis proved to be the most sensitive to raspberry extracts. Contrary to the extracts, sanguiin H-6 and ellagic acid were only active against eight and nine bacterial strains, respectively. The determined MIC and MBC values of both compounds were several times lower than the tested extracts. The highest sensitivity of Corynebacterium diphtheriae to extracts from both black and red raspberries may be due to its sensitivity to sanguiin H-6 and ellagic acid.

The content of ellagic acid was determined from the berries of the family Rosaceae (strawberry, red raspberry, cloudberry, arctic bramble). Extraction and hydrolysis procedures were optimized and analysis was done with an HPLC method and UV detection. The influence of processing on ellagic acid content was studied in strawberry jam. Strawberries, red raspberries, and strawberry jam were analyzed fresh and after 3, 6, and 9 months of storage in a domestic freezer or refrigerator. Ellagic acid contents after 3 months of storage at −20 °C varied between 31.5 (strawberry ‘Senga Sengana’) and 68.6 mg/100 g f.w. (arctic bramble). Ellagic acid content in strawberry jam (23.8 mg/100 g f.w.) was 80% of that in unprocessed strawberries. The content of ellagic acid in strawberries and red raspberries was reduced by 40% and 30%, respectively, during the 9 months of storage at −20°C. The unprocessed berries studied, together with nuts, make the main contribution to the total dietary intake of ellagic acid in Finland.

Red raspberries, valued for their nutrients and bioactive compounds, have broad uses in processing and healthy products. However, limited comprehensive research focused on the comparison of phenolic compounds of red raspberry, especially species cultivated in Northeast China, has been reported. This study aimed to conduct a thorough investigation of 24 red raspberry varieties in Northeast China for the first time, evaluating their phenolic compounds and antioxidant capacities. The results showed that 'DNS1' had the highest total phenolic content (TPC), 'Willamette' had the highest total flavonoid content (TFC), and 'Boyne' had the highest total anthocyanin content (TAC). Phenolic compounds in red raspberries were predominantly found in esterified form, while glycosylated phenolics should not be overlooked. Chlorogenic acid, cryptochlorogenic acid, ellagic acid, and arbutin were the main phenolic compounds, and the distribution of their contents varied between varieties. The antioxidant activity in the red raspberry had a close association with the content of phenolic compounds. Principal component analysis (PCA) showed that phenolic compounds and antioxidant activities were higher in samples from 'DNS1', 'Boyne', 'Beijing10', 'DNS5', and 'Willamette' varieties. These varieties should be given priority in breeding programs that aim to boost the utility and bioactive profile of red raspberries. PRACTICAL APPLICATION: Red raspberry is becoming a desirable commercially grown fruit species and is viewed as a new functional food. In this context, this research offers strong support for confirming the quality of 24 varieties of red raspberry and plays a critical role in the food industry. It also indicates the potential sources of superior varieties of red raspberry, which are advantageous for growers and consumers in search of high-quality red raspberry varieties.

[Figure: see text].

Several studies show that organophosphate pesticides exert several effects on glucose homeostasis. The current study investigates the influence of subchronic exposure to malathion (MT) on hepatic gluconeogenesis in relation to acetyl cholinesterase (AChE) inhibition, oxidative stress and inflammatory response in the rat. MT was administered by gavage at doses of 25, 50 and 100mg/kg for 32 days. Fasting hyperglycemia was seen in line with an increased activity of hepatic phosphoenolpyruvate carboxykinase, glucose 6-phosphatase and tumor necrosis factor α. In addition to the impaired glucose tolerance and inhibition of AChE in a dose-dependent manner, there were significant increases in hepatic lipid peroxidation, carbonyl groups and 8-deoxyguanosine as the biomarkers of reactive oxygen species-mediated damage to lipid, protein and DNA, respectively. Altered quality of the liver in glucose production especially gluconeogenesis could be a compensatory mechanism against MT toxicity or even result in tissue damage. MT-induced insulin resistance in the liver occurs through oxidative and inflammatory signaling pathways.

The term 'inflammation' was first introduced by Celsus almost 2000 years ago. Biological and medical researchers have shown increasing interest in inflammation over the past few decades, in part due to the emerging burden of chronic and degenerative diseases resulting from the increased longevity that has arisen thanks to modern medicine. Inflammation is believed to play critical roles in the pathogenesis of degenerative brain diseases, including Alzheimer's disease and Parkinson's disease. Accordingly, researchers have sought to combat such diseases by controlling inflammatory responses. In this review, we describe the endogenous inflammatory stimulators and signaling pathways in the brain. In particular, our group has focused on the JAK-STAT pathway, identifying anti-inflammatory targets and testing the effects of various anti-inflammatory drugs. This work has shown that the JAK-STAT pathway and its downstream are negatively regulated by phosphatases (SHP2 and MKP-1), inhibitory proteins (SOCS1 and SOCS3) and a nuclear receptor (LXR). These negative regulators are controlled at various levels (e.g. transcriptional, post-transcriptional and post-translational). Future study of these proteins could facilitate the manipulation of the inflammatory response, which plays ubiquitous, diverse and ambivalent roles under physiological and pathological conditions.

Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.

BackgroundNecrotic enteritis is a widespread disease in poultry caused by Clostridium perfringens. We previously reported that dietary arginine supplementation protected the intestinal mucosa of broiler chickens with necrotic enteritis, but the related protective mechanisms remain unclear. The in vivo trial was designed as a 2 × 2 factorial arrangement to evaluated the effects of arginine supplementation on inflammatory responses, arginine transporters, arginine catabolism and JAK-STAT signalling pathway in broiler chickens challenged with C. perfringens or without C. perfringens. Furthermore, we validated the in vivo results using intestinal epithelial cells of chicken embryos.ResultsC. perfringens infection markedly increased gut gross pathological and histopathological lesion scores, promoted liver C. perfringens invasion, reduced serum arginine levels, and elevated jejunal mucosal lysozyme activities (P < 0.05), but these effects were significantly reversed by arginine supplementation in vivo (P < 0.05). The challenge significantly increased serum procalcitonin levels, jejunal mucosal iNOS activities and jejunal IL-6, TGF-β3, cationic amino acid transporter (CAT)-1, and CAT-3 mRNA expression (P < 0.05), whereas arginine supplementation significantly reduced jejunal IFN-γ, IL-1β, IL-6, IL-10, TGF-β3, and CAT-3 mRNA expression (P < 0.05). Arginine supplementation significantly attenuated the C. perfringens challenge-induced increases in jejunal iNOS, arginase 2, arginine decarboxylase, arginine:glycine amidinotransferase, JAK1, JAK3, STAT1, and STAT6 mRNA expression (P < 0.05). The in vitro experiment showed that C. perfringens challenge markedly increased cellular cytotoxicity and the mRNA expression of IL-1β, IL-8, IL-10, CAT-1 and CAT-3 (P < 0.05), which were significantly reversed by 50 μmol/L and/or 400 μmol/L arginine pre-treatment (P < 0.05).ConclusionsArginine prevented C. perfringens challenge-induced circulated arginine deficiency, normalized intestinal arginine transport and catabolism, down-regulated JAK-STAT signalling pathway and attenuated the inflammatory response, which exerted protective effects on the intestine of broiler chickens.

Mechanisms underlying the effect of walnut pellicle extracts and its four representative polyphenols on in vitro digestion of walnut protein isolate

The aim of this study was to quantify the levels of flavonoids (rutin, myricetin, quercetin, kaempferol) and phenolic acids (gallic, p-coumaric, rosmarinic, syringic, caffeic, chlorogenic, ellagic, ferulic) in lemon balm (Melissa officinalis L.) commonly used as a culinary, aromatic and medicinal herb. A rapid and reliable HPLC procedure was developed to determine the phenolic compounds in methanolic extracts, infusions and tinctures prepared from lemon balm. Except for myricetin and quercetin, as well as ellagic, gallic and rosmarinic acids, higher levels of the analytes under study were determined in the methanolic extracts (up to 22 mg/g of dry weight, DW), than in infusions (up to 5 mg/g DW). Tinctures were the poorest in flavonoids and phenolic acids (below 550 μg/g DW), except for ellagic and rosmarinic acids, which were quantified in tinctures at higher levels (mg/g DW). To sum up, the flavonoids were extracted more effectively in the infusions and tinctures than the phenolic acids. Statistically significant correlations were found between phenolic acids, possibly owing to similar biochemical pathways of the compounds. The hierarchical cluster and principal component analyses have also shown that the samples of lemon balm could be differentiated based on the levels of flavonoids and phenolic acids.

EDITORIAL article Front. Cell. Infect. Microbiol., 24 September 2014Sec. Microbiome in Health and Disease Volume 4 - 2014 | https://doi.org/10.3389/fcimb.2014.00134

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

This study reports the utilization of ball-milled achenes in fermentation to increase the levels of ellagic acid and total phenol content, as well as to enhance the antioxidant capacity of strawberry wine. Achenes were micronized using ball-milling process, and then added to strawberry must prior to fermentation. The effects of the addition of ball-milled achenes on the ellagic acid and total phenol content in strawberry wine were determined, and the free radical scavenging and iron chelation activities were also analyzed. Quality attributes and acceptance were studied in comparison with a leading commercial strawberry wine for market application. The particle sizes of achenes were reduced from 1.1mm to 400nm after 30min of ball-milling, and this led to an increase in the amount of extracted ellagic acid from 550.72 to 915.24μg/g. The addition of ball-milled achenes to must led to a 19.72% and 52.37% increase in ellagic acid and total phenol content in strawberry wine, respectively. The increase in bioactive compounds resulted in increases of 54.09%, 51.49% and 56.97% in ABTS and DPPH radical scavenging, and ferrous ion chelating activities, respectively. Although the commercial strawberry wine showed greater aroma intensity, no significant differences in overall quality and acceptance among the conventional process, added ball-milled achenes and the leading commercial strawberry wines were found. This study demonstrates that supplementation of ball-milled achenes in fermentation can be beneficial in increasing the levels of bioactive compounds and antioxidative capacity, indicating a good market potential.

Ample evidence highlights the potential benefits of polyphenols in health status especially in obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, and cardiovascular diseases. Mechanistically, due to the key role of "Metainflammation" in the pathomechanism of metabolic disorders, recently much focus has been placed on the properties of polyphenols in obesity-related morbidities. This narrative review summarizes the current knowledge on the role of polyphenols, including genistein, chlorogenic acid, ellagic acid, caffeic acid, and silymarin in inflammatory responses pertinent to metabolic disorders and discusses the implications of this evidence for future directions. This review provides evidence that the aforementioned polyphenols benefit health status in metabolic disorders via direct and indirect regulation of a variety of target proteins involved in inflammatory signaling pathways. However, due to limitations of the in vitro and in vivo studies and also the lack of long-term human clinical trials studies, further high-quality investigations are required to firmly establish the clinical efficacy of the polyphenols for the prevention and management of metabolic disorders.