Dietary Caffeic Acid Research Articles

Caffeic acid modulates intestinal microbiota, alleviates inflammatory response, and enhances barrier function in a piglet model challenged with lipopolysaccharide.

Young animals are highly susceptible to intestinal damage due to incomplete intestinal development, making them vulnerable to external stimuli. Weaning stress in piglets, for instance, disrupts the balance of intestinal microbiota and metabolism, triggering intestinal inflammation and resulting in gut damage. Caffeic acid (CA), a plant polyphenol, can potentially improve intestinal health. Here, we evaluated the effects of dietary CA on the intestinal barrier and microbiota using a lipopolysaccharide (LPS)-induced intestinal damage model. Eighteen piglets were divided into three groups: control group (CON), LPS group (LPS), and CA + LPS group (CAL). On the 21st and 28th day, six piglets in each group were administered either LPS (80 μg/kg body weight; Escherichia coli O55:B5) or saline. The results showed that dietary CA improved the intestinal morphology and barrier function, and alleviated the inflammatory response. Moreover, dietary CA also improved the diversity and composition of the intestinal microbiota by increasing Lactobacillus and Terrisporobacter while reducing Romboutsia. Furthermore, the LPS challenge resulted in a decreased abundance of 14 different bile acids and acetate, which were restored to normal levels by dietary CA. Lastly, correlation analysis further revealed the potential relationship between intestinal microbiota, metabolites, and barrier function. These findings suggest that dietary CA could enhance intestinal barrier function and positively influence intestinal microbiota and its metabolites to mitigate intestinal damage in piglets. Consuming foods rich in CA may effectively reduce the incidence of intestinal diseases and promote intestinal health in piglets.

An ultrasensitive dietary caffeic acid electrochemical sensor based on Pd-Ru bimetal catalyst doped nano sponge-like carbon

Caffeic acid (CA) is widely present in the human daily diet, and a reliable CA detection method is beneficial to food safety. Herein, we constructed a CA electrochemical sensor employing a glassy carbon electrode (GCE) which was modified by the bimetallic Pd-Ru nanoparticles decorated N-doped spongy porous carbon obtained by pyrolysis of the energetic metal–organic framework (MET). The high-energy bond N-NN in MET explodes to form N-doped sponge-like carbon materials (N-SCs) with porous structures, boosting the adsorptive capacity for CA. The addition of Pd-Ru bimetal improves the electrochemical sensitivity. The linear range of the PdRu/N-SCs/GCE sensor is 1 nM-100 nM and 100 nM-15 μM, with a low detection limit (LOD) of 0.19 nM. It has a high sensitivity (55 μA/μM) and repeatability. The PdRu/N-SCs/GCE sensor has been used to detect CA in actual samples of red wine, strawberries, and blueberries, providing a novel approach for CA detection in food analysis.

Impact of caffeic acid on growth, development and biochemical physiology of insect pest, Spodoptera litura (Fabricius)

The tobacco cutworm, Spodoptera litura (Fabricius) is a serious cosmopolitan pest that attacks several economically important crops such as maize, sorghum, chickpea, pigeon pea, cotton, tobacco and sunflower. It has developed resistance to most pesticides resulting in its continual outbreak. The effect of caffeic acid on second instar larvae of S. litura was evaluated by carrying out bioassays, nutritional assays, immune assays and biochemical assays with phenolic acids. Bioassays carried out with second instar larvae of S. litura showed growth inhibiting effects of various concentrations (5 ppm, 25 ppm, 125 ppm, 625 ppm and 3125 ppm) of caffeic acid on S. litura in comparison to control. A significant increase in mortality as well as an increased development time was observed with increase in the concentration of caffeic acid. A decrease in nutritional indices, including relative growth rate (RGR), relative consumption rate (RCR), efficiency of conversion of ingested food (ECI), efficiency of conversion of digested food (ECD), and approximate digestibility (AD), indicated that dietary caffeic acid also negatively impacted the nutritional physiology of S. litura larvae. Caffeic acid has a significant impact on the immunological response of S. litura larvae. As the concentration of caffeic acid increased, the overall number of hemocytes decreased. Enzymatic assays revealed a significant increase in antioxidant enzymes when S. litura larvae were given an artificial diet containing LC50 concentration of phenolic acid for an interval of 24, 48, 72 and 96 h. The levels of oxidative stress markers (hydrogen peroxide, protein carbonyl and lipid peroxide) were also significantly enhanced in S. litura larvae after treatment with phenolic acid. According to our study, caffeic acid can be employed as a substitute for traditional insecticides to reduce the population of S. litura.

Dietary caffeic acid, ferulic acid and coumaric acid supplements on cholesterol metabolism and antioxidant activity in rats

This study was designed to test the lipid-lowering and antioxidative activities of three phenolic compounds, caffeic acid, ferulic acid and coumaric acid. Four groups of rats were given a semisynthetic diet containing 3% of cholesterol for 6 weeks. The control group only received a high cholesterol diet, whereas the other three groups received a diet including 0.2% of caffeic acid, 0.2% of ferulic acid and 0.2% of coumaric acid. The caffeic acid, ferulic acid and coumaric acid significantly lowered the plasma lipid and hepatic cholesterol levels compared to those in the control (p < 0.05). The hepatic HMG-CoA reductase activity was significantly lower in the caffeic acid group than in the ferulic acid and coumaric acid groups (p < 0.05), while the hepatic ACAT activity was significantly lower in the caffeic acid, ferulic acid and coumaric acid groups compared to the control group (p < 0.05). The overall potential of the antioxidant system was significantly enhanced by the caffeic acid, ferulic acid and coumaric acid supplements as the plasma and hepatic TBARS levels were lowered while the hepatic SOD activities and GSH concentration were elevated in the high-cholesterol-fed rats (p < 0.05). Furthermore, these results indicated that the supplementation of caffeic acid, ferulic acid and coumaric acid boosted the antioxidant activity in rats and promoted the excretion of neutral sterol and acidic sterol (p < 0.05), thereby leading to a decreased absorption of dietary cholesterol as well as lower plasma, hepatic cholesterol and promoted excretion of fecal sterols.

Caffeic Acid Inhibits the Formation of Advanced Glycation End Products (AGEs) and Mitigates the AGEs-Induced Oxidative Stress and Inflammation Reaction in Human Umbilical Vein Endothelial Cells (HUVECs).

The advanced glycation end products (AGEs) are the compounds produced by non-enzymatic glycation reaction of proteins and sugars, which can induce the generation of free radicals and the expression of inflammatory factors, thereby playing an important role in vascular dysfunction in diabetes. To investigate the effects of caffeic acid (CA) on glycation formed by glucose and protein, various spectroscopic techniques and molecular docking methods were carried out. Furthermore, the protective effects of CA on human umbilical vein endothelial cells (HUVECs) damaged by AGEs were detected. The results indicated that CA inhibited AGEs formation in vitro, decreased the expression of IL-1β, IL-18, ICAM-1, VCAM-1, NLRP3, Caspase-1 and CRP (C-reactive protein) and reduced the ROS in HUVECs exposed to AGEs. Our findings suggested that the supplementation with dietary CA could prevent and delay the AGEs-induced vascular dysfunction in diabetes.

Effects of dietary caffeic acid supplement on antioxidant, immunological and liver gene expression responses, and resistance of Nile tilapia, Oreochromis niloticus to Aeromonas veronii

The present study investigated the effects of dietary caffeic acid on haematological, serum biochemical, non-specific immune and liver gene expression responses of Nile tilapia, Oreochromis niloticus. Five experimental groups of fish with mean weights of 89.85 ± 2.5 g were used in the study; three of them were fed with caffeic acid incorporated diets (1 g kg−1-Caf1, 5 g kg−1-Caf5, 10 g kg−1-Caf10), whereas an additive free basal diet served as the control. Additionally, the fifth group was an antibiotic medicated diet (0.02 g kg−1-AMF), prepared with the florfenicol. Dietary caffeic acid especially at 5 g kg−1 significantly increased phagocytic index, potential killing activity, respiratory burst activity, serum myeloperoxidase activity and serum catalase activity. Furthermore, increased levels of immune expression [heat shock protein 70 (HSP70), interleukin 1, beta (IL-1β), tumor necrosis factor (TNF-α), CC-chemokine (CC1), interleukin 8 (IL-8), toll-like receptor 7 (tlr-7), interferon gamma (IFN-γ) and immunoglobulin M (IgM)] and antioxidant related genes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] in the liver of fish fed with 5 g kg−1 caffeic acid. At the end of the 20-day challenge period the survival rates were significantly higher in the Caf5 and AMF groups compared to all other treatment groups.As a result, feeding Nile tilapia with a diet containing 5 g kg−1 caffeic acid over a period of 60 days might be adequate to improve fish immune parameters, antioxidant status, as well as survival rate against A. veronii, similar to antibiotic treatment. Thus caffeic acid can be suggested as a dietary substitute for antibiotic to prevent A. veronii in tilapia.

Caffeic acid ameliorates colitis in association with increased Akkermansia population in the gut microbiota of mice.

Emerging evidence shows that dietary agents and phytochemicals contribute to the prevention and treatment of ulcerative colitis (UC). We first reported the effects of dietary caffeic acid (CaA) on murine experimental colitis and on fecal microbiota. Colitis was induced in C57BL/6 mice by administration of 2.5% dextran sulfate sodium (DSS). Mice were fed a control diet or diet with CaA (1 mM). Our results showed that dietary CaA exerted anti-inflammatory effects in DSS colitis mice. Moreover, CaA could significantly suppress the secretion of IL-6, TNFα, and IFNγ and the colonic infiltration of CD3+ T cells, CD177+ neutrophils and F4/80+ macrophages via inhibition of the activation of NF-κB signaling pathway. Analysis of fecal microbiota showed that CaA could restore the reduction of richness and inhibit the increase of the ratio of Firmicute to Bacteroidetes in DSS colitis mice. And CaA could dramatically increase the proportion of the mucin-degrading bacterium Akkermansia in DSS colitis mice. Thus, CaA could ameliorate colonic pathology and inflammation in DSS colitis mice, and it might be associated with a proportional increase in Akkermansia.

Consumption of Some Polyphenols Reduces Fecal Deoxycholic Acid and Lithocholic Acid, the Secondary Bile Acids of Risk Factors of Colon Cancer

This study was performed to examine the effect of dietary polyphenols on fecal secondary bile acids, such as deoxycholic acid and lithocholic acid, the risk factors of colon cancer, in rats fed a high-fat diet. In experiment 1, rats were fed a 30% beef tallow diet containing 0.5% polyphenols for 3 weeks. Dietary curcumin and caffeic acid significantly reduced the fecal concentration of deoxycholic acid. Dietary caffeic acid, catechin, rutin, and ellagic acid significantly reduced fecal lithocholic acid. Fecal hyodeoxycholic acid, a metabolite of lithocholic acid, was markedly lowered by dietary curcumin, caffeic acid, catechin, and rutin. In experiment 2, rats were fed a 30 or 5% beef tallow diet with or without the addition of 0.5% curcumin. In the rats without receiving curcumin, the fecal level of deoxycholic acid was significantly higher in the high-fat diet group than in the low-fat diet group. Fecal deoxycholic acid was significantly reduced by dietary curcumin in the high-fat diets but not in the low-fat diets. The results suggest novel effects of some polyphenols favorable for colon health by reducing secondary bile acids in animals fed a high-fat diet.

Novel biomarkers of the metabolism of caffeic acid derivatives in vivo

The purpose of this study was to investigate biomarkers of the bioavailability and metabolism of hydroxycinnamate derivatives through the determination of the pharmacokinetics of their urinary elimination and identification of the metabolites excreted. Coffee was used as a rich source of caffeic acid derivatives and human supplementation was undertaken. The results show a highly significant increase in the excretion of ferulic, isoferulic, dihydroferulic acid (3-(4-hydroxy-3-methoxyphenyl)-propionic acid), and vanillic acid postsupplementation relative to the levels presupplementation. Thus, ferulic, isoferulic, and dihydroferulic acids are specific biomarkers for the bioavailability and metabolism of dietary caffeic acid esters. Isoferulic acid is a unique biomarker as it is not a dietary component, however, dihydroferulic acid may well derive from other flavonoids with a structurally related B-ring. 3-Hydroxyhippuric acid has also been identified as an indicator for bioavailability and metabolism of phenolic compounds, and shows a highly significant excretion increase postsupplementation. The results reveal isoferulic acid (and possibly dihydroferulic acid) as novel markers of caffeoyl quinic acid metabolism.

Modulation of ceramide-induced NF-κB binding activity and apoptotic response by caffeic acid in U937 cells: comparison with other antioxidants

Ceramide acts as second messenger in the signal transduction triggered by a variety of stress stimuli and extracellular agents. Stress response through ceramide is involved in the development of many human diseases, such as atherosclerosis, inflammation, neurodegenerative disorders, and acquired immunodeficiency syndrome. Dietary polyphenols have been reported to exert a beneficial effect on the onset and development of most of these human chronic-degenerative pathologies. However, the mechanisms underlying this beneficial effect are mostly not understood at the present. To investigate the ability of polyphenols in modulating fundamental cellular functions, we studied the effect of caffeic acid, a widespread phenolic acid largely present in human diet, in the modulation of ceramide-induced signal transduction pathway leading to apoptosis in U937 cells, in comparison with other established antioxidants of nutritional interest (N-acetylcysteine, d-α-tocopherol acetate and ascorbic acid). Our results indicate that caffeic acid efficiently inhibits both ceramide-induced NF-κB binding activity and apoptosis at μmolar concentration. Other antioxidants tested are totally ineffective in inhibiting apoptosis, although affecting NF-κB activation. Caffeic acid was found to inhibit protein tyrosine kinase activity, suggesting that this mechanism can be on the basis of the inhibition of apoptosis. Our results suggest that dietary caffeic acid might modulate ceramide-induced signal transduction pathway and NF-κB activation through either antioxidant and nonantioxidant mechanisms.