The Bioactive Effects of Chicoric Acid As a Functional Food Ingredient.
Peng Ye,Sun Quancai,Park Yeonhwa
Journal of medicinal food
Chicoric acid, a hydroxycinnamic acid, has been reported to possess a variety of health benefits, including antivirus, antioxidant, anti-inflammation, obesity prevention, and neuroprotection effects. The purpose of this article is to summarize current knowledge of pharmacological and biological effects of chicoric acid. Since most studies to date on chicoric acid have limited their focus to cell cultures and animals, more human and mechanistic studies are therefore needed to further determine the beneficial effects of chicoric acid as a potential functional food ingredient.
10.1089/jmf.2018.0211
Chicoric acid attenuates tumor necrosis factor-α-induced inflammation and apoptosis via the Nrf2/HO-1, PI3K/AKT and NF-κB signaling pathways in C28/I2 cells and ameliorates the progression of osteoarthritis in a rat model.
International immunopharmacology
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.
10.1016/j.intimp.2022.109129
Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway.
Wang Ning,Feng Bai-Nian,Hu Bin,Cheng Yu-Liang,Guo Ya-Hui,Qian He
Food & function
Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (), has been regarded as a nutraceutical to combat inflammation, viruses and obesity. Parkinson's disease (PD) is a common neurodegenerative disorder, and the microbiota-gut-brain axis might be the potential mechanism in the pathogenesis and development of PD. The results obtained in this study demonstrated that oral pretreatments of CA significantly prevented the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunctions and death of nigrostriatal dopaminergic neurons along with the inhibition of glial hyperactivation and the increment in striatal neurotrophins. 16S rRNA sequence results showed that CA significantly reduced MPTP-induced microbial dysbiosis and partially restored the composition of the gut microbiota to normal, including decreased phylum and genera , as well as increased phylum , genera and . Besides, CA promoted colonic epithelial integrity and restored normal SCFA production. We also observed that proinflammatory cytokines such as TNF-α and IL-1β in the serum, striatum and colon were reduced by CA, indicating that CA prevented neuroinflammation and gut inflammation, in which the suppression of the TLR4/MyD88/NF-κB signaling pathway might be the underlying molecular mechanism. These findings demonstrated that CA had neuroprotective effects on MPTP-induced PD mice possibly modulating the gut microbiota and inhibiting inflammation throughout the brain-gut axis.
10.1039/d1fo02216d
Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling.
Abd El-Twab Sanaa M,Hussein Omnia E,Hozayen Walaa G,Bin-Jumah May,Mahmoud Ayman M
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
OBJECTIVE:Chicoric acid (CA) is a natural product with promising antioxidant and anti-inflammatory properties; however, its protective effect on methotrexate (MTX)-induced acute kidney injury (AKI) hasn't been reported. We investigated the effect of CA on MTX-induced AKI in rats, pointing to the role of NF-κB/NLRP3 inflammasome and Nrf2/ARE/HO-1 signaling. MATERIALS AND METHODS:Wistar rats received 25 mg/kg and 50 mg/kg CA for 15 days and a single injection of MTX at day 16. At day 19, the rats were killed, and samples were collected for analyses. RESULTS:MTX induced a significant increase in serum creatinine and urea, and kidney Kim-1, reactive oxygen species (ROS), malondialdehyde and nitric oxide levels. In addition, MTX-induced rats exhibited multiple histopathological alterations, diminished antioxidant defenses, and decreased expression of Nrf2, NQO-1 and HO-1. CA prevented histological alterations, ameliorated kidney function markers, attenuated ROS production and lipid peroxidation, and boosted antioxidant defenses. CA suppressed the expression of NF-κB p65, NLRP3, caspase-1 and IL-1β in the kidney of MTX-induced rats. Furthermore, CA inhibited MTX-induced apoptosis as evidenced by the decreased expression of BAX and caspase-3, and increased Bcl-2 gene expression. CONCLUSIONS:CA prevented MTX-induced AKI through activation of Nrf2/ARE/HO-1 signaling, and attenuation of ROS-induced activation of NF-κB/NLRP3 inflammasome signaling.
10.1007/s00011-019-01241-z
Chicoric acid ameliorate inflammation and oxidative stress in Lipopolysaccharide and d-galactosamine induced acute liver injury.
Li Zheng,Feng Haihua,Han Lu,Ding Lu,Shen Bingyu,Tian Ye,Zhao Lilei,Jin Meiyu,Wang Qi,Qin Haiyan,Cheng Jiaqi,Liu Guowen
Journal of cellular and molecular medicine
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.
10.1111/jcmm.14935
Chicoric acid alleviates lipopolysaccharide-induced acute lung injury in mice through anti-inflammatory and anti-oxidant activities.
Ding Hui,Ci Xinxin,Cheng Hang,Yu Qinlei,Li Dan
International immunopharmacology
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.
10.1016/j.intimp.2018.10.042
Antiradical properties of curcumin, caffeic acid phenethyl ester, and chicoric acid: a DFT study.
Manzanilla Brenda,Robles Juvencio
Journal of molecular modeling
The antiradical properties and possible mechanisms of action of the tautomers of curcumin, caffeic acid phenethyl ester (CAPE), and chicoric acid (CA) have been studied within density functional theory (DFT). We calculated global chemical reactivity descriptors from conceptual DFT, pK, bioavailability, and toxicity to evaluate the antiradical properties and characterize these species. Our final level of theory is the M06-2X functional with the 6-31 + G* basis set; we selected this level after performing a benchmark calibration and validation among different levels. Solvent effects were modeled via the continuum solvation model based on density (SMD). We used water and pentyl ethanoate as solvents to simulate the physiological conditions. The free radical scavenger capacity was analyzed for three possible oxidative stress mechanisms: single electron transfer (SET), hydrogen atom transfer (HAT), and xanthine oxidase (XO) inhibition. The results indicate that neutral curcumin, CA, and CAPE behave as antireductants. The most favorable mechanism turns out to be HAT, where CA and CAPE stand out. In conclusion, our DFT study strongly indicates that neutral curcumin, CAPE, and CA would very likely perform well as antiradical drugs with recommended therapeutic use, supported by their non-toxic nature.
10.1007/s00894-022-05056-4
Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis.
Duan Huxinyue,Zhang Qing,Liu Jia,Li Ruolan,Wang Dan,Peng Wei,Wu Chunjie
Pharmacological research
Atherosclerosis, a chronic multifactorial disease, is closely related to the development of cardiovascular diseases and is one of the predominant causes of death worldwide. Normal vascular endothelial cells play an important role in maintaining vascular homeostasis and inhibiting atherosclerosis by regulating vascular tension, preventing thrombosis and regulating inflammation. Currently, accumulating evidence has revealed that endothelial cell apoptosis is the first step of atherosclerosis. Excess apoptosis of endothelial cells induced by risk factors for atherosclerosis is a preliminary event in atherosclerosis development and might be a target for preventing and treating atherosclerosis. Interestingly, accumulating evidence shows that natural medicines have great potential to treat atherosclerosis by inhibiting endothelial cell apoptosis. Therefore, this paper reviewed current studies on the inhibitory effect of natural medicines on endothelial cell apoptosis and summarized the risk factors that may induce endothelial cell apoptosis, including oxidized low-density lipoprotein (ox-LDL), reactive oxygen species (ROS), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α), homocysteine (Hcy) and lipopolysaccharide (LPS). We expect this review to highlight the importance of natural medicines, including extracts and monomers, in the treatment of atherosclerosis by inhibiting endothelial cell apoptosis and provide a foundation for the development of potential antiatherosclerotic drugs from natural medicines.
10.1016/j.phrs.2021.105599
Protective effects of chicoric acid on LPS-induced endometritis in mice via inhibiting ferroptosis by Nrf2/HO-1 signal axis.
International immunopharmacology
Chicoric acid (CA), a natural phenolic acid extracted from Mediterranean vegetable chicory, has anti-oxidative effect. We aimed to investigate the effects of CA on endometritis and clarify the underlying mechanism. C57BL/6 mice were divided into five groups: control group, LPS group, and LPS + CA groups. All mice except control group were infused of LPS into the uterus. The mice of LPS + CA groups were intraperitoneally injected CA 1 h before LPS challenge. CA significantly alleviatedLPS-induced pathological damage, MPO activity, and inflammatory cytokine production. CA significantly suppressed ferroptosis in LPS-induced endometritis. CA also attenuated LPS-induced NF-κB activation. Furthermore, Nrf2 and HO-1 expression were increased by CA. Moreover, the inhibition of CA on LPS-induced endometritis and ferroptosis were markedly prevented in Nrf2 knockdown mice. In conclusion, the results suggested CA protected mice against LPS-induced endometritisthrough inhibiting ferroptosis via Nrf2/HO-1 signaling pathway.
10.1016/j.intimp.2022.109435
Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model.
The American journal of Chinese medicine
Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the model. Meanwhile, BMDM cells were stimulated with LPS+ATP to build the model. CA significantly alleviated inflammation and oxidative stress in both the and models of ALI through the inhibition of NLR family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. In addition, CA attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis in the and models of ALI by suppressing the production of reactive oxygen species (ROS) via inhibiting the Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. CA inhibited the interaction between Akt at T308 and phosphoinositide-dependent kinase-1 (PDPK1) at S549, thus promoting the phosphorylation of the Akt protein. Furthermore, CA directly targeted the PDPK1 protein and accelerated PDPK1 ubiquitination, indicating that 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP, and 223-ASP might be responsible for the interaction between PDPK1 and CA. In conclusion, CA from alleviated NLRP3-mediated pyroptosis in the ALI model through ROS-induced mitochondrial damage by activating Akt/Nrf2 pathway via PDPK1 ubiquitination. The present study suggests that CA might be a potential therapeutic drug to treat or prevent ALI in pneumonia or COVID-19.
10.1142/S0192415X23500659
Optimized Extraction of Polyphenols from Unconventional Edible Plants: LC-MS/MS Profiling of Polyphenols, Biological Functions, Molecular Docking, and Pharmacokinetics Study.
Molecules (Basel, Switzerland)
Plant bioactive phenolic metabolites have recently attracted the attention of researchers due to their numerous health advantages. Therefore, this study aimed to investigate with advanced techniques the bioactive metabolites and antioxidant and antidiabetic capacity of four unconventional edible plant leaves: lemongrass ( (DC.) Stapf), chicory ( L.), moringa ( Lam.), and ryegrass ( L.). The extraction process was optimized using different solvents. These plants' phenolic composition, identification, and characterization have been determined herein using LCESI-QTOF-MS/MS. This research identified 85 phenolic compounds, including 24 phenolic acids, 31 flavonoids, 7 stilbenes and lignans, and 17 other metabolites. Moreover, the study determined that moringa has the highest total phenolic content (TPC; 18.5 ± 1.01 mg GAE/g), whereas ryegrass has the lowest (3.54 ± 0.08 mg GAE/g) among the selected plants. It seems that, compared to other plants, moringa was found to have the highest antioxidant potential and antidiabetic potential. In addition, twenty-two phenolic compounds were quantified in these chosen edible plants. Rosmarinic acid, chlorogenic acid, chicoric acid, ferulic acid, protocatechuic acid, and caffeic acid were the most abundant phenolic acids. In silico molecular docking was also conducted to investigate the structure-function relationship of phenolic compounds to inhibit the alpha-glucosidase. Finally, the simulated pharmacokinetic characteristics of the most common substances were also predicted. In short, this investigation opens the way for further study into these plants' pharmaceutical and dietary potential.
10.3390/molecules28186703
Chicoric acid enhances the antioxidative defense system and protects against inflammation and apoptosis associated with the colitis model induced by dextran sulfate sodium in rats.
Environmental science and pollution research international
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.
10.1007/s11356-023-30742-y
Chicoric acid ameliorates LPS-induced inflammatory injury in bovine lamellar keratinocytes by modulating the TLR4/MAPK/NF-κB signaling pathway.
Scientific reports
Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P < 0.01), down-regulated the expression of TLR4, MyD88, p-ERK, p-p38, IKKβ, p-p65, p-p50 (P < 0.05), and increased the IκBα protein expression (P < 0.05). In conclusion, Chicoric acid successfully protected cow lamellar keratinocytes from LPS-induced inflammatory responses by modulating the TLR4/MAPK/NF-κB signaling pathway and downregulating inflammatory mediators.
10.1038/s41598-023-49169-z
An Insight into the Promising Therapeutic Potential of Chicoric Acid.
Current pharmaceutical biotechnology
The pharmacological treatments that are now recommended for the therapy of chronic illnesses are examined in a great number of studies to determine whether or not they are both safe and effective. Therefore, it is important to investigate various alternative therapeutic assistance, such as natural remedies derived from medicinal plants. In this context, chicoric acid, classified as a hydroxycinnamic acid, has been documented to exhibit a range of health advantages. These include antiviral, antioxidant, anti-inflammatory, obesity-preventing, and neuroprotective effects. Due to its considerable pharmacological properties, chicoric acid has found extensive applications in food, pharmaceuticals, animal husbandry, and various other commercial sectors. This article provides a comprehensive overview of in vitro and in vivo investigations on chicoric acid, highlighting its beneficial effects and therapeutic activity when used as a preventative and management aid for public health conditions, including diabetes, cardiovascular disease, and hepatic illnesses like non-alcoholic steatohepatitis. Moreover, further investigation of this compound can lead to its development as a potential phytopharmaceutical candidate.
10.2174/0113892010280616231127075921
Chicoric acid inserted in protein Z cavity exhibits higher stability and better wound healing effect under oxidative stress.
International journal of biological macromolecules
Oxidative stress is one of the limiting factors that inhibit wound healing. Phytochemicals especially chicoric acid have the potential to act as an antioxidant and scavenge reactive oxygen species, thereby promoting wound healing. However, most of the phytochemicals were easy to be degraded during storage or using due to the oxidative status in wound site. Herein, we introduce a high stable protein Z that can encapsulate chicoric acid during foaming. TEM results showed that the size of protein Z-chicoric acid is in the range of nanoscale (named PZ-CA nanocomposite), and protein Z encapsulation can significantly improve the stability of chicoric acid under oxidative stress. Moreover, PZ-CA nanocomposite exhibited favorable antioxidant properties, biocompatibility, and the ability to promote cell migration in vitro. The role of PZ-CA nanocomposite in skin regeneration was explored by a mice model. Results in vivo suggest that the PZ-CA nanocomposite promotes wound healing with a faster rate as compared with a commercial spray solution, mostly through attenuating the oxidative stress, promoting cell proliferation and collagen deposition. This work not only provides a delivery vector for bioactive molecules, but also develops a kind of nanocomposite with the property of promoting wound healing.
10.1016/j.ijbiomac.2023.128823
Chicoric acid attenuates hyperglycemia-induced endothelial dysfunction through AMPK-dependent inhibition of oxidative/nitrative stresses.
Journal of receptor and signal transduction research
BACKGROUND: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. METHODS:In the present study, human umbilical vein endothelial cells (HUVECs) were incubated with high glucose/high fat (HG + HF) to induce endothelial cell injury. RESULTS: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. CONCLUSION: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.
10.1080/10799893.2020.1817076
Chicoric Acid: Natural Occurrence, Chemical Synthesis, Biosynthesis, and Their Bioactive Effects.
Frontiers in chemistry
Chicoric acid has been widely used in food, medicine, animal husbandry, and other commercial products because of its significant pharmacological activities. However, the shortage of chicoric acid limits its further development and utilization. Currently, (L.) Moench serves as the primary natural resource of chicoric acid, while other sources of it are poorly known. Extracting chicoric acid from plants is the most common approach. Meanwhile, chicoric acid levels vary in different plants as well as in the same plant from different areas and different medicinal parts, and different extraction methods. We comprehensively reviewed the information regarding the sources of chicoric acid from plant extracts, its chemical synthesis, biosynthesis, and bioactive effects.
10.3389/fchem.2022.888673
Chicoric Acid Ameliorates Nonalcoholic Fatty Liver Disease via the AMPK/Nrf2/NFB Signaling Pathway and Restores Gut Microbiota in High-Fat-Diet-Fed Mice.
Ding Xiaoqin,Jian Tunyu,Li Jiawei,Lv Han,Tong Bei,Li Jing,Meng Xiuhua,Ren Bingru,Chen Jian
Oxidative medicine and cellular longevity
This study examines the effects of chicoric acid (CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat-diet- (HFD-) fed C57BL/6 mice. CA treatment decreased body weight and white adipose weight, mitigated hyperglycemia and dyslipidemia, and reduced hepatic steatosis in HFD-fed mice. Moreover, CA treatment reversed HFD-induced oxidative stress and inflammation both systemically and locally in the liver, evidenced by the decreased serum malondialdehyde (MDA) abundance, increased serum superoxide dismutase (SOD) activity, lowered reactive oxygen species (ROS) in the liver, decreased serum and hepatic inflammatory cytokine levels, and reduced hepatic inflammatory cell infiltration in HFD-fed mice. In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells. In particular, we identified AMPK as an activator of Nrf2 and an inactivator of NFB. CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFB protein level both in HFD mice and PA-treated HepG2 cells. Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA. Similarly, Nrf2 inhibitor ML385 partly blocked the regulation of antioxidative genes and ROS overproduction by CA in PA-treated HepG2 cells. Interestingly, high-throughput pyrosequencing of 16S rRNA suggested that CA could increase -to- ratio and modify gut microbial composition towards a healthier microbial profile. In summary, CA plays a preventative role in the amelioration of oxidative stress and inflammation via the AMPK/Nrf2/NFB signaling pathway and shapes gut microbiota in HFD-induced NAFLD.
10.1155/2020/9734560
Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPARγ and Nrf2/HO-1 signaling.
Environmental science and pollution research international
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.
10.1007/s11356-020-08557-y
Methylated Metabolites of Chicoric Acid Ameliorate Hydrogen Peroxide (HO)-Induced Oxidative Stress in HepG2 Cells.
Chang Xiaowen,Dong Shan,Bai Wenliang,Di Yan,Gu Ruijuan,Liu Fuguo,Zhao Beita,Wang Yutang,Liu Xuebo
Journal of agricultural and food chemistry
Chicoric acid (CA) can display health benefits as a dietary polyphenol. However, as CA is widely metabolized , the actual compounds responsible for its bioactivities are not entirely known. Herein, the major methylated metabolites of CA were isolated from an co-incubation system, and their structures were elucidated. The antioxidant activities of the monomethylated metabolites (M1) and dimethylated metabolites (M2) of CA were evaluated against HO-induced oxidative stress damage in HepG2 cells and compared to CA. The results indicated that both M1 and M2 had better antioxidant capacities than CA by increasing cell viability, improving mitochondrial function, and balancing cellular redox status. These compounds also prevented oxidative stress by mediating the Keap1/Nrf2 transcriptional pathway and downregulating enzyme activity. The current research indicates that the methylated metabolites of CA could potentially be the candidates that are responsible for the biological efficacies attributed to CA.
10.1021/acs.jafc.0c07521
Chicoric Acid Prevents Neuroinflammation and Neurodegeneration in a Mouse Parkinson's Disease Model: Immune Response and Transcriptome Profile of the Spleen and Colon.
Wang Ning,Li Rui,Feng Bainian,Cheng Yuliang,Guo Yahui,Qian He
International journal of molecular sciences
Chicoric acid (CA), a polyphenolic acid compound extracted from chicory and echinacea, possesses antiviral, antioxidative and anti-inflammatory activities. Growing evidence supports the pivotal roles of brain-spleen and brain-gut axes in neurodegenerative diseases, including Parkinson's disease (PD), and the immune response of the spleen and colon is always the active participant in the pathogenesis and development of PD. In this study, we observe that CA prevented dopaminergic neuronal lesions, motor deficits and glial activation in PD mice, along with the increment in striatal brain-derived neurotrophic factor (BDNF), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HT). Furthermore, CA reversed the level of interleukin-17(IL-17), interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) of PD mice, implicating its regulatory effect on the immunological response of spleen and colon. Transcriptome analysis revealed that 22 genes in the spleen (21 upregulated and 1 downregulated) and 306 genes (190 upregulated and 116 downregulated) in the colon were significantly differentially expressed in CA-pretreated mice. These genes were functionally annotated with GSEA, GO and KEGG pathway enrichment, providing the potential target genes and molecular biological mechanisms for the modulation of CA on the spleen and gut in PD. Remarkably, CA restored some gene expressions to normal level. Our results highlighted that the neuroprotection of CA might be associated with the manipulation of CA on brain-spleen and brain-gut axes in PD.
10.3390/ijms23042031
Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway.
Ding Xiao-Qin,Jian Tun-Yu,Gai Ya-Nan,Niu Guan-Ting,Liu Yan,Meng Xiu-Hua,Li Jing,Lyu Han,Ren Bing-Ru,Chen Jian
Journal of agricultural and food chemistry
As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. , the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.
10.1021/acs.jafc.1c07795
Cichoric acid improved hyperglycaemia and restored muscle injury via activating antioxidant response in MLD-STZ-induced diabetic mice.
Zhu Di,Zhang Xinglin,Niu Yajie,Diao Zhijun,Ren Bo,Li Xingyu,Liu Zhigang,Liu Xuebo
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Cichoric acid (CA), extracted from edible plants and vegetables, is a potential natural nutraceutical, with antioxidant and hypoglycaemic biological functions. The objective of this study was to explore the potential underlying molecular mechanisms involved in normalizing diabetes-related changes in hyperglycaemia via pancreas apoptosis and muscle injury induced by multiple low-dose STZ (MLD-STZ) injection in response to dietary supplementation with CA. To induce the MLD-STZ diabetic mice, the C57BL/6J mice were intraperitoneally injected with STZ (50 mg/kg body weight) for consecutive five days. CA (60 mg/kg/d) was supplemented in drinking water for 4 weeks. Compared with control, CA inhibited pancreas apoptosis and adjusted islet function in diabetic mice, leading to an increase in insulin generation and secretion. Moreover, CA regulated mitochondrial biogenesis, glycogen synthesis, and inhibited inflammation via activating antioxidant responses, which contributes to the improvement in athletic ability and diabetic myopathy. In general, CA is a natural food-derived compound with the potential application for regulating glucose homeostasis and improving diabetes and its complications.
10.1016/j.fct.2017.06.041
Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade.
Lu Qing-Bo,Wan Ming-Yu,Wang Pei-Yao,Zhang Chen-Xing,Xu Dong-Yan,Liao Xiang,Sun Hai-Jian
Redox biology
Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by increased expressions of VSMC synthetic markers and decreased levels of VSMC contractile markers, which is an important step for VSMC proliferation and migration during the development and progression of cardiovascular diseases including atherosclerosis. Chicoric acid (CA) is identified to exert powerful cardiovascular protective effects. However, little is known about the effects of CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)-induced VSMC phenotypic alteration, proliferation and migration. Mechanistically, PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and P70S6K phosphorylation, which was attenuated by CA pretreatment, diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) and nuclear factor-κB (NFκB) inhibitor Bay117082. PDGF-BB-triggered ROS production and p65-NFκB activation were inhibited by CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFκB nuclear translocation, phosphorylation and degradation of Inhibitor κBα (IκBα). Of note, blockade of ROS/NFκB/mTOR/P70S6K signaling cascade prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. CA treatment prevented intimal hyperplasia and vascular remodeling in rat models of carotid artery ligation in vivo. These results suggest that CA impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and neointima formation via inhibition of ROS/NFκB/mTOR/P70S6K signaling cascade.
10.1016/j.redox.2017.11.012
Chicoric acid mitigates impaired insulin sensitivity by improving mitochondrial function.
Kim Ji-Sun,Lee Hyunjung,Jung Chang Hwa,Lee Sung-Joon,Ha Tae-Youl,Ahn Jiyun
Bioscience, biotechnology, and biochemistry
Mitochondrial dysfunction is associated with insulin resistance. Although chicoric acid (CA) is known to have beneficial effects on insulin sensitivity, the involvement of mitochondrial function has not been elucidated yet. Here, we investigated the effect of CA on insulin resistance and mitochondrial dysfunction. In palmitate-induced insulin-resistant C2C12 myotubes, CA improved impaired glucose uptake and insulin signaling pathways, along with enhanced mitochondrial membrane potential and oxygen consumption. CA treatment in diet-induced obese mice ameliorated glucose tolerance and increased insulin sensitivity. CA treatment also recovered the dysregulated expression of glucose metabolism-related genes in the high-fat-fed mice. CA significantly increased the mitochondrial DNA content, citrate synthase, and ATP content, as well as the expression of genes related to mitochondrial biogenesis and oxidative phosphorylation in the liver and skeletal muscle in high-fat- fed obese mice. These findings suggested that CA attenuates insulin resistance and promotes insulin sensitivity by enhancing mitochondrial function.
10.1080/09168451.2018.1451742
MAPK pathway mediates the anti-oxidative effect of chicoric acid against cerebral ischemia-reperfusion injury .
Experimental and therapeutic medicine
The aim of the present study was to investigate the protective effect of chicoric acid on oxidative stress and inflammation in rats with cerebral ischemia-reperfusion injury. A cerebral ischemia-reperfusion injury rat model was created via transient middle cerebral artery occlusion (MCAO) and rats were treated with various doses of chicoric acid (0, 1, 10 and 100 mg/kg). Neurological deficits and infarct volume were used to estimate the protective effects of chicoric acid treatment. Levels of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO) and prostaglandin E2 (PGE2) were assessed. Western blot analysis was also used to measure the expression of cyclooxygenase (COX)-2, p38-mitogen activated protein kinase (MAPK), c-Jun, phosphorylated protein kinase B (p-AKT) and AKT. Chicoric acid exposure was observed to reduce neurological deficits and infarct volume in rats with cerebral ischemia-reperfusion injury. In addition, ROS production and inflammation were significantly suppressed following treatment with chicoric acid. Chicoric acid was demonstrated to significantly inhibit the upregulation of NO and PGE2 levels in rats following MCAO. Furthermore, chicoric acid significantly suppressed the MCAO-induced promotion of COX-2, p38-MAPK and c-Jun protein expression and enhanced the inhibition of p-AKT/AKT. These results suggest that chicoric acid has a protective effect, preventing oxidative stress and inflammation in rats with cerebral ischemia-reperfusion injury via the p38-MAPK, c-Jun and AKT signaling pathways.
10.3892/etm.2017.5598
Chicoric Acid Improves Heart and Blood Responses to Hypobaric Hypoxia in Tibetan Yaks.
Wu Hua,Luo Dan,Li Changxing,Zhang Hui,Shunxian A,Zhang Yuanxin,Sun Chao
The American journal of Chinese medicine
Yak is a wild bovine species living on the Qinghai Tibet Plateau that demonstrates good adaptability to the hypoxic environment. Chicoric acid, a natural phenolic compound, is known as having anti-oxidant, antiviral, anti-inflammatory and analgesic properties. However, its effect on hypoxia adaptability of yak is still unclear. In this study 40 yaks were selected that were of similar age, parity and weight, and divided into the control group and experimental groups 1, 2, 3, randomly. Results showed that chicoric acid significantly improved RBC, HGB, and WBC. There are significantly beneficial effects to increasing total protein contents ([Formula: see text]): all treatments increased HDL-C contents, and supplementations 100[Formula: see text]mg/h significantly decreased the content of TG on the 60th day ([Formula: see text]). Contents of the serum related enzymes like ALP, GOP and GPT showed varying degrees of change, but no significant differences and the indexes of anti-oxidant capacity (T-AOC and GSH-Px) were significantly improved ([Formula: see text]), but MDA was decreased ([Formula: see text]) under the action of the chicoric acid. Hypoxia-inducible factor in serum such as HIF-2[Formula: see text], EPO, ROS, Fe[Formula: see text] and Tf are all significantly decreased ([Formula: see text]). The myocardial mitochondrial parameters mtDNA, UCP2, PGC1-[Formula: see text], NRF1 and mitochondrial complexes were altered remarkably. Some indicators of glucose metabolism presented variation trends. Taken together, chicoric acid has shown a positive effect on the adaptive ability of yak in high altitude, hypoxic environment in plateau areas. Our findings reported a new potential means to enhance immunity and inflammatory response and improve the anti-oxidant capacity.
10.1142/S0192415X18500179
Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action and anti-inflammation capacity.
Tsai Kun-Ling,Kao Chung-Lan,Hung Ching-Hsia,Cheng Yung-Hsin,Lin Huei-Chen,Chu Pei-Ming
Oncotarget
Atherosclerotic cardiovascular disease is linked to both oxidative stress and endothelial cell dysfunction. Chicoric acid has antioxidant and anti-inflammatory properties. In the present investigation, we demonstrated that chicoric acid inhibits oxidized low-density lipoprotein (oxLDL)-facilitated dysfunction in human umbilical vein endothelial cells (HUVECs). Oxidative injuries were tested by investigating the formation of intracellular reactive oxygen species (ROS) and by examining the activity of antioxidant enzymes and the function of endothelial nitric oxide synthase (eNOS). We also confirmed that chicoric acid mitigates apoptotic features caused by oxLDL, such as the subsequent break down of mitochondrial transmembrane potential and the activation of Bax, which promote DNA strand breaks and activate caspase-3. Moreover, our data revealed that chicoric acid attenuated the oxLDL activation of NF-κB, the attachment of THP-1 cells and the overexpression of adhesion molecules in human endothelial cells. The results of this study suggest a potential molecular mechanism through which chicoric acid inhibits oxLDL-induced human endothelial dysfunction.
10.18632/oncotarget.16768