chicoric-acid and Inflammation

Although several anticolitic drugs are available, their application is associated with numerous side effects. Chicoric acid (CA) is a hydroxycinnamic acid found naturally in chicory (Cichorium intybus), purple coneflower (Echinacea purpurea), and basil with numerous health benefits, such as antioxidative and anti-inflammatory activities. Here, the potential anticolitic efficiency of CA against dextran sulfate sodium (DSS)-induced colitis in rats was examined in rats. Animals were randomly assigned to the following five groups: control, CA (100 mg/kg body weight), DSS [(DSS); 4% w/v], CA + DSS (100 mg/kg), and the 5-aminosalicylic acid (100 mg/kg) + DSS group. The obtained data revealed that CA significantly prevented the shortening of colon length. Meanwhile, the oxidative stress-related enzymes were increased, while malondialdehyde and nitric oxide, were markedly decreased significantly by CA. The results also indicated that CA administration decreased significantly the pro-apoptogenic indices (Bax and caspase-3) and enhanced significantly Bcl-2, the anti-apoptogenic protein. Moreover, DSS caused a significant elevation of pro-inflammatory mediators, including interleukin-1β, tumor necrosis factor-α, myeloperoxidase, cyclooxygenase II, prostaglandin E2, and peroxisome proliferator-activated receptor gamma. Interestingly, these changes were significantly decreased following the CA administration. At the molecular level, CA supplementation has increased significantly the expression level of nuclear factor erythroid 2-related factor-2 (Nrf2) and decreased the expressions of nitric oxide synthase and mitogen-activated protein kinase 14. CA has been determined to significantly lessen DSS-induced colitis by activating Nrf2 and its derived antioxidant molecules and suppressing inflammation and apoptosis cascades associated with the development of colitis; suggesting that CA could be used as an alternative naturally-derived anticolitic agent.

Topics: Animals; Antioxidants; Apoptosis; Colitis; Dextran Sulfate; Disease Models, Animal; Inflammation; NF-E2-Related Factor 2; Rats

Virus induced damage triggered by excessive inflammation and free radical production is a major threat in the poultry industry, leading to low productivity even in vaccinated flocks. The purpose of the study was to induce inflammation with the viral double-stranded RNA analog polyinosinic-polycytidylic acid (poly I:C) on chicken primary hepatocyte - non-parenchymal cell co-cultures to investigate the immunomodulatory and cell protectant effects of chicoric acid (CA) in comparison to N-acetylcysteine (NAC). Poly I:C significantly elevated the activity of the cell damage marker, lactate dehydrogenase (LDH) and the concentration of inflammatory cytokines (IL-6, IL-8, IFN-α, IFN-γ and M-CSF) in the culture medium and decreased cellular metabolic activity. CA significantly reduced the elevated LDH and cytokine levels in a dose-dependent manner, moreover, the higher (100 µg/mL) concentration of CA even elevated the level of metabolic activity. In contrast, 10 µg/mL NAC treatment decreased the level of each inflammatory cytokine but did not rectify cell damage or metabolic depression. The results indicate, that CA, present in common plants of the Asteraceae family, proves to be a beneficial hepatoprotective, and along with NAC, an immunomodulatory supplement in vitro under a stimulus mimicking viral infection.

Topics: Animals; Caffeic Acids; Cell Culture Techniques; Chickens; Cytokines; Hepatocytes; Inflammation; Poly I-C; Succinates

Osteoarthritis (OA) is the most common arthritis, and is characterized by inflammation and cartilage degradation. Chicoric acid (CA), a bioactive caffeic acid derivative isolated from the root of Taraxacum mongolicumHand. - Mazz., has been reported to have anti-inflammatory effects. However, the therapeutic effects of CA on chondrocyte inflammation remain unknown. Our study aimed to explore the effect of CA on OA both in vivo and in vitro. In vitro, CA treatment significantly suppressed the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and IL-12 in tumor necrosis factor alpha (TNF-α)-induced human C28/I2 chondrocytes. Moreover, CA attenuated TNF-α induced degradation of the extracellular matrix (ECM) by upregulating the expression of collagen Ⅱ and aggrecan, and downregulating ADAMTS-5 and matrix metalloproteinases (MMPs). Additionally, CA treatment inhibited apoptosis in C28/I2 cells by upregulating of Bcl-2 levels, downregulating Bax and ROS levels, and activating the Nrf2/HO-1 pathway. Mechanistically, CA exerted an anti-inflammatory effect by inhibiting the PI3K/AKT and NF-κB signaling pathways, enhancing Nrf-2/HO-1 to limit the activation of NF-κB. In vivo experiments also proved the therapeutic effects of CA on OA in rats. These findings indicate that CA may become a new drug for the treatment of OA.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Caffeic Acids; Chondrocytes; Humans; Inflammation; Interleukin-1beta; Interleukin-6; NF-E2-Related Factor 2; NF-kappa B; Osteoarthritis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Succinates; Tumor Necrosis Factor-alpha

Endothelial dysfunction is a driving force during the development and progression of cardiovascular complications in diabetes. Targeting endothelial injury may be an attractive avenue for the management of diabetic vascular disorders. Chicoric acid is reported to confer antioxidant and anti-inflammatory properties in various diseases including diabetes. However, the role and mechanism of chicoric acid in hyperglycemia-induced endothelial damage are not well understood.. In the present study, human umbilical vein endothelial cells (HUVECs) were incubated with high glucose/high fat (HG + HF) to induce endothelial cell injury.. We found that exposure of HUVECs to HG + HF medium promoted the release of cytochrome c (cytc) from mitochondrion into the cytoplasm, stimulated the cleavage of caspase-3 and poly ADP-ribose-polymerase (PARP), then inducing cell apoptosis, the effects that were prevented by administration of chicoric acid. Besides, we found that chicoric acid diminished HG + HF-induced phosphorylation and degradation of IκBα, and subsequent p65 NFκB nuclear translocation, thereby contributing to its anti-inflammatory effects in HUVECs. We also confirmed that chicoric acid mitigated oxidative/nitrative stresses under HG + HF conditions. Studies aimed at exploring the underlying mechanisms found that chicoric acid activated the AMP-activated protein kinase (AMPK) signaling pathway to attenuate HG + HF-triggered injury in HUVECs as AMPK inhibitor Compound C or silencing of AMPKα1 abolished the beneficial effects of chicoric acid in HUVECs.. Collectively, chicoric acid is likely protected against diabetes-induced endothelial dysfunction by activation of the AMPK signaling pathway. Chicoric acid could be a novel candidate for the treatment of the diabetes-associated vascular endothelial injury.

Topics: AMP-Activated Protein Kinases; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Caffeic Acids; Cell Survival; Cytochromes c; Cytoplasm; Endothelium, Vascular; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Inflammation; L-Lactate Dehydrogenase; Mitochondria; Nitrosative Stress; Oxidative Stress; Poly(ADP-ribose) Polymerases; RNA, Small Interfering; Succinates

Chicoric acid is polyphenol of natural plant and has a variety of bioactivity. Caused by various kinds of stimulating factors, acute liver injury has high fatality rate. The effect of chicoric acid in acute liver injury induced by Lipopolysaccharide (LPS) and d-galactosamine (d-GalN) was investigated in this study. The results showed that CA decreased the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and reduced the mortality induced by LPS/d-GalN. CA can restrain mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) to alleviate inflammation. Meanwhile, the results indicated CA can active nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway with increasing the level of AMP-activated protein kinase (AMPK). And with the treatment of CA, protein levels of autophagy genes were obvious improved. The results of experiments indicate that CA has protective effect in liver injury, and the activation of AMPK and autophagy may make sense.

Topics: Alanine Transaminase; AMP-Activated Protein Kinase Kinases; Animals; Aspartate Aminotransferases; Autophagy; Caffeic Acids; Chemical and Drug Induced Liver Injury; Galactosamine; Gene Expression Regulation; Hep G2 Cells; Humans; Inflammation; Lipopolysaccharides; Liver; Mice; Mitogen-Activated Protein Kinase Kinases; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Protein Kinases; Succinates

Chicoric acid (CA) is a natural antioxidant with promising hepatoprotective activity. We investigated the potential of CA to prevent methotrexate (MTX) hepatotoxicity, pointing to the role of Nrf2/HO-1 signaling and PPARγ. Rats received CA for 15 days and were then injected with MTX at day 16. Blood and tissue samples were collected for analysis at day 19. CA ameliorated liver function markers and mitigated histological alterations in MTX-induced rats. Pre-treatment with CA suppressed reactive oxygen species and lipid peroxidation and enhanced antioxidants in MTX-induced rats. Moreover, CA upregulated hepatic Nrf2, HO-1, NQO-1, and PPARγ, and attenuated inflammation. Consequently, CA inhibited apoptosis by increasing Bcl-2 expression and suppressing Bax, cytochrome c, and caspase-3 in MTX-administered rats. In conclusion, CA prevented oxidative stress, inflammation, and liver injury induced by MTX by activating Nrf2 /HO-1 signaling and PPARγ.

Topics: Animals; Antioxidants; Caffeic Acids; Chemical and Drug Induced Liver Injury; Inflammation; Liver; Methotrexate; NF-E2-Related Factor 2; Oxidative Stress; PPAR gamma; Rats; Rats, Wistar; Succinates; Up-Regulation

Acute lung injury (ALI) is a severe clinical disease with high mortality rates. Chicoric acid (CA), an active component extracted from traditional Chinese medicine, was suggested to have anti-inflammatory and anti-oxidant activities. Inflammation and oxidative damage are implicated in the pathogenesis of ALI. In this study, we explored the protection effect of CA on LPS-induced ALI, and further discussed the possible molecular mechanisms. The results showed that CA could significantly improve the histological changes of LPS-induced acute lung injury. In addition, CA not only decreased LPS-stimulated protein leakage and lung wet/dry ratio but also reduced inflammatory cell infiltration, myeloperoxidase (MPO) activity and the generation of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF). Meanwhile, CA lessened the reactive oxygen species (ROS) generation, and malondialdehyde (MDA) formation, and decreased glutathione (GSH) and superoxide dismutase (SOD) depletion, which were caused by LPS challenge. Furthermore, CA dramatically inhibited LPS-stimulated MAPK and NLRP3 activation and increased the expression of NAD (P) H: quinone oxidoreductase (NQO1), and dismutase (SOD), glutamate-cysteine ligase catalytic/modifier (GCLC/GCLM) subunit and heme oxygenase-1 (HO-1), as well as its upstream genes nuclear factor-erythroid 2-related factor 2 (Nrf2), which might be central to the protective effects of CA. In conclusion, these data indicated that the protective effects and mechanisms of CA on LPS-induced ALI and provided new insights for its application.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Caffeic Acids; Cytokines; Disease Models, Animal; Humans; Inflammation; Lipopolysaccharides; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Signal Transduction; Succinates

Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation. 20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP-activated protein kinase (AMPK) and phospho-AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real-time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting. IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non-obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level. These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.

Topics: Adult; AMP-Activated Protein Kinases; Anti-Inflammatory Agents; Caffeic Acids; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Male; Middle Aged; Neutrophils; Palmitates; Sirtuin 1; Succinates

Nonalcoholic fatty liver diseases (NAFLD) range histopathologically from hepatic steatosis to steatohepatitis. Chicoric acid has beneficial effects on obesity and liver injury, but its effects on nonalcoholic steatohepatitis (NASH) have not yet been determined. This study examined the effects of Crepidiastrum denticulatum extract (CDE) and its active compound chicoric acid in a mouse model of NASH and fibrosis.. CDE and chicoric acid were orally administrated to mice fed a methionine- and choline-deficient (MCD) diet. HepG2 and AML-12 cells in MCD medium were incubated with chicoric acid. MCD-fed mice developed the histopathological characteristics of human NASH, including altered regulation of lipid metabolism, inflammation, fibrosis, and oxidation-associated expression, along with augmented lipoperoxidation. Administration of CDE or chicoric acid to MCD-fed mice and HepG2 and AML-12 cells in MCD medium reduced oxidative stress by upregulating antioxidant enzymes and decreased inflammation by inhibiting proinflammatory cytokines and nuclear factor-κB activation. In addition, CDE or chicoric acid reduced fibrosis, apoptosis, and lipogenesis-related gene expression and increased AMP Kinase activation both in vivo and in vitro.. CDE and chicoric acid may be effective in the treatment of NAFLD and NASH.

Topics: Animals; Asteraceae; Caffeic Acids; Cell Line; Choline Deficiency; Disease Models, Animal; Hep G2 Cells; Hepatocytes; Humans; Inflammation; Lipid Metabolism; Liver Cirrhosis; Male; Methionine; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Plant Extracts; Succinates

Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model. Therefore, we investigated the antiallergic-related anti-inflammatory effect of chicoric acid and its underlying mechanisms of action using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated HMC-1 cells. Chicoric acid decreased the mRNA expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. We studied the inhibitory effects of chicoric acid on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, we investigated the ability of chicoric acid to inhibit compound 48/80-induced systemic anaphylaxis in vivo. Oral administration of chicoric acid at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. These results suggest that chicoric acid has an antiallergic-related anti-inflammatory effect that involves modulating mast cell-mediated allergic responses. Therefore, chicoric acid could be an efficacious agent for allergy-related inflammatory disorders.

Topics: Animals; Anti-Allergic Agents; Caffeic Acids; Caspase 1; Cytokines; Disease Models, Animal; Histamine Release; Humans; Inflammation; Interleukin-1beta; Male; Mast Cells; Mice; Mitogen-Activated Protein Kinases; Molecular Structure; NF-kappa B; p-Methoxy-N-methylphenethylamine; p38 Mitogen-Activated Protein Kinases; Phorbol Esters; Succinates

Cichoric acid, a caffeic acid derivative found in Echinacea purpurea, basil, and chicory, has been reported to have bioactive effects, such as anti-inflammatory, antioxidant, and preventing insulin resistance. In this study, to explore the effects of CA on regulating insulin resistance and chronic inflammatory responses, the insulin resistance model was constructed by glucosamine in HepG2 cells. CA stimulated glucosamine-mediated glucose uptake by stimulating translocation of the glucose transporter 2. Moreover, the production of reactive oxygen, the expression of COX-2 and iNOS, and the mRNA levels of TNF-α and IL-6 were attenuated. Furthermore, CA was verified to promote glucosamine-mediated glucose uptake and inhibited inflammation through PI3K/Akt, NF-κB, and MAPK signaling pathways in HepG2 cells. These results implied that CA could increase glucose uptake, improve insulin resistance, and attenuate glucosamine-induced inflammation, suggesting that CA is a potential natural nutraceutical with antidiabetic properties and anti-inflammatory effects.

Topics: Anti-Inflammatory Agents; Caffeic Acids; Dietary Supplements; Glucosamine; Glucose; Glucose Transporter Type 2; Hep G2 Cells; Humans; Hypoglycemic Agents; Inflammation; Insulin Resistance; Liver; Signal Transduction; Succinates

Synergistic anti-inflammatory effects of luteolin and chicoric acid, two abundant constituents of the common dandelion (Taraxacum officinale Weber), were investigated in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Co-treatment with luteolin and chicoric acid synergistically reduced cellular concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) and also inhibited expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, co-treatment reduced the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Both luteolin and chicoric acid suppressed oxidative stress, but they did not exhibit any synergistic activity. Luteolin and chicoric acid co-treatment inhibited phosphorylation of NF-κB and Akt, but had no effect on extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. This anti-inflammatory signaling cascade coincides with that affected by luteolin treatment alone. These results suggest that luteolin plays a central role in ameliorating LPS-induced inflammatory cascades via inactivation of the NF-κB and Akt pathways, and that chicoric acid strengthens the anti-inflammatory activity of luteolin through NF-κB attenuation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Caffeic Acids; Cell Line; Dinoprostone; Drug Synergism; Gene Expression Regulation; Inflammation; Inflammation Mediators; Lipopolysaccharides; Luteolin; Mice; NF-kappa B; Nitric Oxide; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Subunits; Protein Transport; Proto-Oncogene Proteins c-akt; Signal Transduction; Succinates