Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,ma...Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.展开更多
The interactions of chlorogenic acid （CA）, neochlorogenic acid （NCA） and cryptochlorogenic acid （CCA） with lysozyme （LYSO） were investigated in physiological buffer by fluorescence spectroscopy. The mechanism ...The interactions of chlorogenic acid （CA）, neochlorogenic acid （NCA） and cryptochlorogenic acid （CCA） with lysozyme （LYSO） were investigated in physiological buffer by fluorescence spectroscopy. The mechanism study indicated that CA, NCA and CCA could strongly quench the intrinsic fluorescence of LYSO through static quenching procedures with one binding site. Thermodynamic data show that the major force in the binding processes of CA to LYSO was hydrophobic interactions; for NCA, it was the hydrogen bonds and van der Waals forces, as for the CCA system, the mainly force is electrostatic force.展开更多
[Objectives]To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of forsythin,baicalin,and chlorogenic acid in a traditional Chinese medicine spray disinfectant.[Methods...[Objectives]To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of forsythin,baicalin,and chlorogenic acid in a traditional Chinese medicine spray disinfectant.[Methods]The chromatographic separation was performed on a GL Sciences(19H0044724)-C_(18)column(4.6 mm×250 mm,5μm)with a mobile phase of acetonitrile-0.05%formic acid solution at a flow rate of 1 mL/min.The injection volume was 10μL,detection wavelength was set at 280 nm,and column temperature was maintained at 25℃.[Results]The linear ranges of forsythin,baicalin,and chlorogenic acid were 10.5-52.5,20.6-103,and 14.2-71μg/mL,respectively,with good linear relationships between concentration and peak area(R^(2)=0.9999).The relative standard deviations(RSD s)for precision and repeatability tests were all≤1.0%.The average recoveries were 98.51%,98.48%,and 97.71%for the three components,with RSD s of 0.96%,0.97%,and 0.73%,respectively.[Conclusions]This method demonstrates strong specificity,high precision,excellent accuracy,and simplicity of operation,making it suitable for the simultaneous quantification of forsythin,baicalin,and chlorogenic acid in traditional Chinese medicine spray disinfectants.It provides a reliable basis for quality control and practical applications in animal breeding environments.展开更多
Background:Cadmium(Cd)exposure disrupts bone microstructure and elevates osteoporosis risk,warranting innovative functional food development to alleviate its toxic effects.This study evaluated the protective effects o...Background:Cadmium(Cd)exposure disrupts bone microstructure and elevates osteoporosis risk,warranting innovative functional food development to alleviate its toxic effects.This study evaluated the protective effects of calcium(Ca)and chlorogenic acid(CGA)against Cd-induced bone damage,intestinal injury,and gut microbiota dysbiosis in rats.Methods:Thirty-two female Sprague-Dawley rats were allocated to four groups:control(Con),Cd-exposed(Cd),Cd+calcium gluconate(Ca),and Cd+CGA(CGA).Eight weeks after the experiment,histopathological analyses of bone and intestinal tissues,Cd content measurements,and gut microbiota composition assessments were conducted.Concurrently,serum superoxide dismutase(SOD)activity was determined.Results:Cd exposure significantly increased serum SOD levels and bone Cd levels(P<0.05),which was significantly attenuated under Ca and CGA interventions,with CGA showing superior efficacy(P<0.05).Histological analysis revealed Cd-induced trabecular resorption and adipocyte proliferation in bone,which were ameliorated by both interventions.CGA administration significantly improved intestinal morphological parameters(villous height,crypt depth)and reduced Chiu scores(P<0.05),whereas Ca had limited impact.Gut microbiota analysis indicated Cd exposure induced microbial dysbiosis,characterized by elevatedα-diversity indices(Chao1 and Shannon),which Ca partially stabilized by enriching beneficial taxa(e.g.,Lactobacillaceae).Conversely,CGA reduced microbial diversity but enhanced barrier-related metabolic pathways(e.g.,nucleotide biosynthesis).Both Ca and CGA interventions effectively reduced Proteobacteria abundance and partially restored the Firmicutes/Bacteroidetes(F/B)ratio,However,genus-level responses diverged significantly:Ca specifically enriched Blautia;CGA,in contrast,promoted Bifidobacterium and Oscillospira.Conclusion:Ca and CGA differentially protect against Cd toxicity.Integrating Ca-fortified foods(via competitive inhibition of Cd absorption)with CGA-rich extracts(via antioxidant activity and microbiota modulation)may provide dual-targeted functional formulations for Cd-exposed populations.展开更多
Chlorogenic acid(CGA),as a polyphenol abundant in daily diet,exerted various intestinal functions.However,the material basis of its intestinal bioactivities was still unclear.Our study investigated the gastrointestina...Chlorogenic acid(CGA),as a polyphenol abundant in daily diet,exerted various intestinal functions.However,the material basis of its intestinal bioactivities was still unclear.Our study investigated the gastrointestinal distribution of CGA using ultra high performance liquid chromatography-tandem mass spectrum(UPLC-MS/MS)and explored the main drivers leading to different metabolic fates of the metabolites.After oral administration of 50 mg/kg bw CGA to mice,CGA and sulfated metabolites were mainly determined in small intestine.Protocatechuic acid,catechol,and 3-hydroxyphenylpropionic acid were found in copious amounts in large intestine and feces.Besides,caffeic acid existed in the entire intestine and feces.In the in vitro mice/human fecal fermentation of CGA,the production of metabolites was consistent with that in the colon,indicating that microorganisms might lead to the difference in the gastrointestinal distribution of CGA metabolites.Moreover,CGA,3-hydroxyphenylpropionic acid,protocatechuic acid,catechol,and caffeic acid reduced proinflammatory cytokines(interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α))and increased mucin(Muc2)and tight junction(occludin)mRNA in LPS-induced Caco-2/HT-29 MTX co-culture cells.In conclusion,the biotransformation of CGA in different gastrointestinal tracts varied significantly,and its metabolites could partially support its intestinal bioactivities.展开更多
Background Systemic inflammatory responses and oxidative stress occur in laying hens during the aging process,particularly during the post-peaking laying period,which generally result in multi-organ damages,leading to...Background Systemic inflammatory responses and oxidative stress occur in laying hens during the aging process,particularly during the post-peaking laying period,which generally result in multi-organ damages,leading to significant declines in egg performance and quality.Chlorogenic acid(CGA)-enriched extract from Eucommia ulmoides leaves has anti-inflammatory and antioxidant activities.However,the mechanisms underlying whether and how CGA alleviates systemic inflammatory responses and oxidative stress to improve egg performance and quality in postpeaking laying hens remain unclear.In this study,the potential regulatory mechanisms of CGA in alleviating inflammatory responses and oxidative stress along the gut-liver axis were investigated.A total of 36055-week-old Hy-line white-laying hens were randomly selected and divided into four groups.The hens in the four groups were fed a basal diet(CON)or basal diets supplemented with 200,400,and 800 mg/kg of CGA(CGA200,CGA400,and CGA800,respectively)for 10 weeks.Results The results demonstrated that CGA significantly alleviated intestinal and hepatic damages resulting from systemic inflammatory responses and oxidative stress,thereby improving the laying performance and egg quality of post-peaking laying hens.CGA reduced systemic inflammation by improving intestinal barrier function and modulating inflammation-associated microbiota(Blautia and Megamonas),thus inhibiting endotoxin translocation.CGA can also reduce oxidative stress by upregulating the NRF-2 pathway-related genes and increasing antioxidant enzyme activities in the liver.The results of transcriptome sequencing revealed that CGA promoted lipid metabolism by regulating hepatic adipocytokine pathway-related genes/protein and reduced the inflammatory responses and apoptosis in liver by regulating PI3K/AKT pathway-related genes/proteins,which was also verified by qPCR and western blotting.Conclusion CGA alleviated multi-organ damages and dysfunction by suppressing the systemic inflammatory responses and oxidative stress in post-peaking laying hens,thereby improving egg performance and quality.The optimal dose of CGA is 400 mg/kg in this experiment.These results provide a sound theoretical basis for the application of CGA as an exogenous animal feed additive for laying hens.展开更多
Chlorogenic acid(CGA),a potent antioxidant with antimicrobial,antiviral,and metabolic regulatory properties,plays multifunctional roles in apple fruit by enhancing postharvest quality,extending shelf life through oxid...Chlorogenic acid(CGA),a potent antioxidant with antimicrobial,antiviral,and metabolic regulatory properties,plays multifunctional roles in apple fruit by enhancing postharvest quality,extending shelf life through oxidative stress reduction,and inhibiting enzymatic browning to preserve color,flavor,and nutritional integrity.Despite the established role of hydroxycinnamoyl transferase(HCT)as a rate-limiting enzyme in CGA biosynthesis,the specific HCT gene responsible for this process and its regulatory mechanisms remain elusive.To address this knowledge gap,we systematically investigated CGA accumulation dynamics during apple storage and functionally characterized MdHCT6,a candidate gene within the HCT family.We found that the chlorogenic acid content in apple fruit increased significantly during postharvest storage compared with the initial storage.Transcriptome analysis showed that the expression level of MdHCT6 was significantly higher than that of other HCT homologues,which was consistent with the reverse transcription quantitative PCR(RT-qPCR)results.In vitro enzymatic assays demonstrated that MdHCT6 catalyzes the synthesis of chlorogenic acid using shikimic acid and quinic acid as precursors,while genetic evidence confirmed its role as a key positive regulator of chlorogenic acid accumulation in apples.Furthermore,we identified the transcription factor MdMYB93 as a direct upstream activator of MdHCT6,establishing a regulatory cascade that governs CGA production.This work not only deciphers the molecular hierarchy of CGA biosynthesis in apples but also provides actionable targets for genetic improvement of antioxidant capacity and postharvest resilience in apple germplasm.展开更多
Background Deoxynivalenol(DON)is a mycotoxin that severely pollutes feed ingredients,and methods for reducing DON toxicity have become a significant research direction.Chlorogenic acid(CGA)is an active polyphenol foun...Background Deoxynivalenol(DON)is a mycotoxin that severely pollutes feed ingredients,and methods for reducing DON toxicity have become a significant research direction.Chlorogenic acid(CGA)is an active polyphenol found in some plants,which has anti-inflammatory and antioxidant properties and a protective effect on animal intestinal health.The effects of CGA on DON-induced pyroptosis in the intestinal porcine epithelial cell line-J2(IPEC-J2)and its potential mechanism were explored in this study.Results IPEC-J2 cells viability and membrane integrity were inversely correlated with DON concentration.Compared to those in the group treated with DON alone at 2,500 ng/mL,pretreatment with 80μmol/L CGA for 4 h significantly improved cell viability(P<0.01),and the alleviation of typical pyroptotic symptoms induced by DON were observed,including reduced cellular DNA fragmentation,decreased release of lactate dehydrogenase(LDH),normalized ROS levels,restoration of extracellularCa2+andK+contents to normal levels(P<0.01),as well as suppressed the enzyme activities of caspase-1 and caspase-4(P<0.01).Additionally,the mRNA expression levels of TNF,MDP,NOD2,TLR4,ASC and GSDMD were significantly improved(P<0.01),while both mRNA and protein expression levels of NF-κB,NLRP3,caspase-1,IL-1βand IL-18 were significantly upregulated(P<0.01)in the CGA+DON group,compare to those in the DON group.Conclusion Pretreatment with 80μmol/L CGA for 4 h effectively alleviated pyroptosis in IPEC-J2 cells induced by 2,500 ng/mL of DON through inhibiting activation of the NF-κB/NLRP3/capase-1 pathway.展开更多
Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidativ...Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.展开更多
Chlorogenic acid(CA)is a natural plant-derived polyphenol compound that is widely present in beverages(coffee and tea),fruits(blueberry,apple,and mulberry),and medicinal plants(Lonicera japonica,Eucommia ulmoides,and ...Chlorogenic acid(CA)is a natural plant-derived polyphenol compound that is widely present in beverages(coffee and tea),fruits(blueberry,apple,and mulberry),and medicinal plants(Lonicera japonica,Eucommia ulmoides,and Cichorium intybus).In recent years,CA has attracted extensive attention due to its various health benefits,such as anti-inflammatory,immunomodulatory,anti-obesity,anti-diabetes mellitus,and neuroprotection activities.Interestingly,the low bioavailability of CA corresponds to high bioactivity,which raises a key scientifi c question of how low bioavailability CA can achieve high biological activity.In this review,we highlight the gut microbiota as a key target for connecting the two by summarizing a large amount of evidence.Specifi cally,the composition and abundance of gut microbiota,its metabolites,intestinal immunity,barrier function and so on were all changed under different pathological conditions such as infl ammatory bowel disease,liver disease,kidney disease,cardiovascular disease,diabetes mellitus,obesity,etc.Conversely,these changes could be reversed by CA.In a word,CA could achieve pharmacological activity as well as health-protective effects by modulating intestinal immune and barrier function,gut microbiota composition,gut microbiota metabolites,and signaling pathways.This review provides new targets for the prevention and treatment of diseases by CA.Meanwhile,regulating the composition of the gut microbiota through natural products may be a potential strategy to achieve health protection.展开更多
BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxida...BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a novel ferroptosis inducer or anti-HCC drug.展开更多
Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α...Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.展开更多
Flos Lonicerae is a medically useful traditional Chinese medicine herb. However, little is known about the antioxidant properties of Flos Lonicerae extracts. Here the antioxidant capacity of water, methanolic and etha...Flos Lonicerae is a medically useful traditional Chinese medicine herb. However, little is known about the antioxidant properties of Flos Lonicerae extracts. Here the antioxidant capacity of water, methanolic and ethanolic extracts prepared from Flos Lonicerae to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduce Fe3+ to Fe2+ is examined. Chlorogenic acid, a major component of Flos Lonicerae, is identified and further purified from 70% ethanolic extract with high performance liquid chromatography (HPLC) and its antioxidant capacity is characterized. The total phenolic compounds and chlorogenic acid con-tents in Flos Lonicerae are determined. The present results demonstrate that the Flos Lonicerae extracts exhibit antioxidant ac-tivity and chlorogenic acid is a major contributor to this activity.展开更多
The present study was designed to establish and optimize a new method for extracting chlorogenic acid and cynaroside from Lonicera japonica Thunb. through orthogonal experimental designl. A new ultrahigh pressure extr...The present study was designed to establish and optimize a new method for extracting chlorogenic acid and cynaroside from Lonicera japonica Thunb. through orthogonal experimental designl. A new ultrahigh pressure extraction （UPE） technology was applied to extract chlorogenic acid and cynaroside from L. japonica. The influential factors, including solvent type, ethanol concentration, extraction pressure, time, and temperature, and the solid/liquid ratio, have been studied to optimize the extraction process, The optimal conditions for the UPE were developed by quantitative analysis of the extraction products by HPLC-DAD in comparison with standard samples. In addition, the microstructures of the medicinal materials before and after extraction were studied by scanning electron microscopy （SEM）. Furthermore, the extraction efficiency of different extraction methods and the 2, 2-diphenyl-1-picrylhydrazyl （DPPH） radical scavenging activities of the extracts were investigated. The optimal conditions for extracting chlorogenic acid and cynaroside were as follows： ethanol concentration, 60%; extraction pressure, 400 MPa; extraction time, 2 rain; extraction temperature, 30 ℃; and the solid/liquid ratio, 1 ： 50. Under these conditions, the yields of chlorogenic acid and cynaroside were raised to 4.863% and 0.080%, respectively. Compared with other extraction methods, such as heat reflux extraction （HRE）, ultrasonic extraction （UE）, and Sohxlet extraction （SE）, the UPE method showed several advantages, including higher extraction yield, shorter extraction time, lower energy consumption, and higher purity of the extracts. This study could help better utilize L. japonica flower buds as a readily accessible source of natural antioxidants in food and pharmaceutical industries.展开更多
Chlorogenic acid(5-CQA),neochlorogenic acid(3-CQA),and cryptochlorogenic acid(4-CQA),usually simultaneously exist in many traditional Chinese medicines(TCMs).However,insufficient attentions have been paid to the compa...Chlorogenic acid(5-CQA),neochlorogenic acid(3-CQA),and cryptochlorogenic acid(4-CQA),usually simultaneously exist in many traditional Chinese medicines(TCMs).However,insufficient attentions have been paid to the comparative metabolism study on these three isomeric constituents with similar effects on anti-inflammation until now.In this study,a novel strategy was established to perform comparative analysis of their metabolic fates in rats and elucidate the pharmacological mechanism of antiinflammation.Firstly,diagnostic product ions(DPIs)deduced from the representative reference standards were adopted to rapidly screen and characterize the metabolites in rat plasma,urine and faeces using UHPLC-Q-TOF MS.Subsequently,Network pharmacology was utilized to elucidate their anti-inflammatory mechanism.Consequently,a total of 73 metabolites were detected and characterized,including 50,47 and 43 metabolites for 5-CQA,4-CQA and 3-CQA,orderly.Moreover,the network pharmacology study indicated that these three isomeric constituents and their major metabolites with similar in vivo metabolic pathways exerted anti-inflammatory effects through co-owned 20 biological processes,which involved 10 major signal pathways and 159 potential targets.Our study shed light on the similarities and differences of the metabolic profiling and anti-inflammatory activity among these three isomeric constituents and set an example for the further researches on the active mechanism of isomeric constituents existing in TCMs based on comparative metabolism study.展开更多
Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC...Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.展开更多
Chlorogenic acid（CGA）, a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen（AP）-induced hepatotoxicity a...Chlorogenic acid（CGA）, a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen（AP）-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase（ALT/AST） in vivo. The effect of CGA on cytochrome P450（CYP） enzymatic（CYP2E1, CYP1A2, and CYP3A4） activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde（MDA）, reactive oxygen species（ROS）, and glutathione（GSH） levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased m RNA expression of peroxiredoxin（Prx） 1, 2, 3, 5, 6, epoxide hydrolase（Ephx） 2, and polymerase（RNA） II（DNA directed） polypeptide K（Polr2k）, and nuclear factor erythroid-2-related factor 2（Nrf2）. In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2 k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.展开更多
Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we ...Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.展开更多
Sweetpotato[Ipomoea batatas(L.)Lam.],a food crop with both nutritional and medicinal uses,plays essential roles in food security and health-promoting.Chlorogenic acid(CGA),a polyphenol displaying several bioactivities...Sweetpotato[Ipomoea batatas(L.)Lam.],a food crop with both nutritional and medicinal uses,plays essential roles in food security and health-promoting.Chlorogenic acid(CGA),a polyphenol displaying several bioactivities,is distributed in all edible parts of sweetpotato.However,little is known about the specific metabolism of CGA in sweetpotato.In this study,IbPAL1,which encodes an endoplasmic reticulum-localized phenylalanine ammonia lyase(PAL),was isolated and characterized in sweetpotato.CGA accumulation was positively associated with the expression pattern of IbPAL1 in a tissue-specific manner,as further demonstrated by overexpression of IbPAL1.Overexpression of IbPAL1 promoted CGA accumulation and biosynthetic pathway genes expression in leaves,stimulated secondary xylem cell expansion in stems,and inhibited storage root formation.Our results support a potential role for IbPAL1 in sweetpotato CGA biosynthesis and establish a theoretical foundation for detailed mechanism research and nutrient improvement in sweetpotato breeding programs.展开更多
In this study,chlorogenic acid(CGA),a phenolic compound widely distributed in fruits and vegetables,was encapsulated into chitosan nanoparticles by ionic gelation method.The particles exhibited the size and zeta poten...In this study,chlorogenic acid(CGA),a phenolic compound widely distributed in fruits and vegetables,was encapsulated into chitosan nanoparticles by ionic gelation method.The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively.A regular,spherical shaped distribution of nanoparticles was observed through scanning electron microscopy(SEM)and the success of entrapment was confirmed by FTIR analysis.The encapsulation efficiency of CGA was at about 59%with the loading efficiency of 5.2%.In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further,the release kinetics study revealed the burst release of 69%CGA from nanoparticles at the end of 100th hours.Pharmacokinetic analysis in rats showed a lower level of Cmax,longer Tmax,longer MRT,larger AUC0et and AUC0e∞for the CGA nanoparticles compared to free CGA.Collectively,these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.展开更多
基金supported by National Key R&D Program of China(2023YFD1301200)China Agriculture Research Systems(CARS-40-K11)+2 种基金Beijing Agriculture Innovation Consortium(BAIC06-2024-G05)Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(NCTIP-XD/C08)The Chinese Academy of Agricultural Science and Technology Innovation Project(ASTIP-IAS-12)。
文摘Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.
文摘The interactions of chlorogenic acid （CA）, neochlorogenic acid （NCA） and cryptochlorogenic acid （CCA） with lysozyme （LYSO） were investigated in physiological buffer by fluorescence spectroscopy. The mechanism study indicated that CA, NCA and CCA could strongly quench the intrinsic fluorescence of LYSO through static quenching procedures with one binding site. Thermodynamic data show that the major force in the binding processes of CA to LYSO was hydrophobic interactions; for NCA, it was the hydrogen bonds and van der Waals forces, as for the CCA system, the mainly force is electrostatic force.
基金Supported by Shandong Province Major Agricultural Technologies Collaborative Promotion Project(SDNYXTTG-2024-04)National Key Laboratory for Quality Control of Chinese Medicinal Materials and Decoction Pieces Project(2024GSMPA-KL16)Weifang Municipal Science and Technology Bureau Project(2021GX031).
文摘[Objectives]To establish a high-performance liquid chromatography(HPLC)method for the simultaneous determination of forsythin,baicalin,and chlorogenic acid in a traditional Chinese medicine spray disinfectant.[Methods]The chromatographic separation was performed on a GL Sciences(19H0044724)-C_(18)column(4.6 mm×250 mm,5μm)with a mobile phase of acetonitrile-0.05%formic acid solution at a flow rate of 1 mL/min.The injection volume was 10μL,detection wavelength was set at 280 nm,and column temperature was maintained at 25℃.[Results]The linear ranges of forsythin,baicalin,and chlorogenic acid were 10.5-52.5,20.6-103,and 14.2-71μg/mL,respectively,with good linear relationships between concentration and peak area(R^(2)=0.9999).The relative standard deviations(RSD s)for precision and repeatability tests were all≤1.0%.The average recoveries were 98.51%,98.48%,and 97.71%for the three components,with RSD s of 0.96%,0.97%,and 0.73%,respectively.[Conclusions]This method demonstrates strong specificity,high precision,excellent accuracy,and simplicity of operation,making it suitable for the simultaneous quantification of forsythin,baicalin,and chlorogenic acid in traditional Chinese medicine spray disinfectants.It provides a reliable basis for quality control and practical applications in animal breeding environments.
基金supported by Guizhou Provincial Basic Research Program(Natural Science)(Qiankeheji-ZK[2021]General 497)Guizhou Health and Wellness Commission Science and Technology Fund Project(2024-247)Guizhou University of Traditional Chinese Medicine Academic Seedling Program(Guizhou Kehe Academic Seedling[2023]-35),The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Institutional Research Grants(GZEYK[2020-34]).
文摘Background:Cadmium(Cd)exposure disrupts bone microstructure and elevates osteoporosis risk,warranting innovative functional food development to alleviate its toxic effects.This study evaluated the protective effects of calcium(Ca)and chlorogenic acid(CGA)against Cd-induced bone damage,intestinal injury,and gut microbiota dysbiosis in rats.Methods:Thirty-two female Sprague-Dawley rats were allocated to four groups:control(Con),Cd-exposed(Cd),Cd+calcium gluconate(Ca),and Cd+CGA(CGA).Eight weeks after the experiment,histopathological analyses of bone and intestinal tissues,Cd content measurements,and gut microbiota composition assessments were conducted.Concurrently,serum superoxide dismutase(SOD)activity was determined.Results:Cd exposure significantly increased serum SOD levels and bone Cd levels(P<0.05),which was significantly attenuated under Ca and CGA interventions,with CGA showing superior efficacy(P<0.05).Histological analysis revealed Cd-induced trabecular resorption and adipocyte proliferation in bone,which were ameliorated by both interventions.CGA administration significantly improved intestinal morphological parameters(villous height,crypt depth)and reduced Chiu scores(P<0.05),whereas Ca had limited impact.Gut microbiota analysis indicated Cd exposure induced microbial dysbiosis,characterized by elevatedα-diversity indices(Chao1 and Shannon),which Ca partially stabilized by enriching beneficial taxa(e.g.,Lactobacillaceae).Conversely,CGA reduced microbial diversity but enhanced barrier-related metabolic pathways(e.g.,nucleotide biosynthesis).Both Ca and CGA interventions effectively reduced Proteobacteria abundance and partially restored the Firmicutes/Bacteroidetes(F/B)ratio,However,genus-level responses diverged significantly:Ca specifically enriched Blautia;CGA,in contrast,promoted Bifidobacterium and Oscillospira.Conclusion:Ca and CGA differentially protect against Cd toxicity.Integrating Ca-fortified foods(via competitive inhibition of Cd absorption)with CGA-rich extracts(via antioxidant activity and microbiota modulation)may provide dual-targeted functional formulations for Cd-exposed populations.
基金funded by National Natural Science Foundation of China(32101962)the Science and Technology Program of Tianjin,China(Grant number 22JCQNJC01200)+1 种基金the Natural Science Foundation of Zhejiang Province,China(LY21B060007)the Horizontal Project(KYY-HX-20210848).
文摘Chlorogenic acid(CGA),as a polyphenol abundant in daily diet,exerted various intestinal functions.However,the material basis of its intestinal bioactivities was still unclear.Our study investigated the gastrointestinal distribution of CGA using ultra high performance liquid chromatography-tandem mass spectrum(UPLC-MS/MS)and explored the main drivers leading to different metabolic fates of the metabolites.After oral administration of 50 mg/kg bw CGA to mice,CGA and sulfated metabolites were mainly determined in small intestine.Protocatechuic acid,catechol,and 3-hydroxyphenylpropionic acid were found in copious amounts in large intestine and feces.Besides,caffeic acid existed in the entire intestine and feces.In the in vitro mice/human fecal fermentation of CGA,the production of metabolites was consistent with that in the colon,indicating that microorganisms might lead to the difference in the gastrointestinal distribution of CGA metabolites.Moreover,CGA,3-hydroxyphenylpropionic acid,protocatechuic acid,catechol,and caffeic acid reduced proinflammatory cytokines(interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α))and increased mucin(Muc2)and tight junction(occludin)mRNA in LPS-induced Caco-2/HT-29 MTX co-culture cells.In conclusion,the biotransformation of CGA in different gastrointestinal tracts varied significantly,and its metabolites could partially support its intestinal bioactivities.
基金financially supported by the Collaborative Extension Program for Advancements in Agricultural Technologies of Zhejiang Province(Grant no:2023ZDXT15)the Key Research&Development Program of Zhejiang Province(Grant no:2024C02004)Bureau of Science and Technology of Xinchang County Foundation.
文摘Background Systemic inflammatory responses and oxidative stress occur in laying hens during the aging process,particularly during the post-peaking laying period,which generally result in multi-organ damages,leading to significant declines in egg performance and quality.Chlorogenic acid(CGA)-enriched extract from Eucommia ulmoides leaves has anti-inflammatory and antioxidant activities.However,the mechanisms underlying whether and how CGA alleviates systemic inflammatory responses and oxidative stress to improve egg performance and quality in postpeaking laying hens remain unclear.In this study,the potential regulatory mechanisms of CGA in alleviating inflammatory responses and oxidative stress along the gut-liver axis were investigated.A total of 36055-week-old Hy-line white-laying hens were randomly selected and divided into four groups.The hens in the four groups were fed a basal diet(CON)or basal diets supplemented with 200,400,and 800 mg/kg of CGA(CGA200,CGA400,and CGA800,respectively)for 10 weeks.Results The results demonstrated that CGA significantly alleviated intestinal and hepatic damages resulting from systemic inflammatory responses and oxidative stress,thereby improving the laying performance and egg quality of post-peaking laying hens.CGA reduced systemic inflammation by improving intestinal barrier function and modulating inflammation-associated microbiota(Blautia and Megamonas),thus inhibiting endotoxin translocation.CGA can also reduce oxidative stress by upregulating the NRF-2 pathway-related genes and increasing antioxidant enzyme activities in the liver.The results of transcriptome sequencing revealed that CGA promoted lipid metabolism by regulating hepatic adipocytokine pathway-related genes/protein and reduced the inflammatory responses and apoptosis in liver by regulating PI3K/AKT pathway-related genes/proteins,which was also verified by qPCR and western blotting.Conclusion CGA alleviated multi-organ damages and dysfunction by suppressing the systemic inflammatory responses and oxidative stress in post-peaking laying hens,thereby improving egg performance and quality.The optimal dose of CGA is 400 mg/kg in this experiment.These results provide a sound theoretical basis for the application of CGA as an exogenous animal feed additive for laying hens.
基金supported by grants from the National Key Research and Development Program of China(Grant Nos.2023YFD2301000,2022YFD2100102)National Natural Science Foundation of China(Grant No.32302616)+1 种基金Shandong Province(Grant No.ZR2023QC032)the Key Research and Development Program of Shandong Province(Grant No.2023CXGC010709).
文摘Chlorogenic acid(CGA),a potent antioxidant with antimicrobial,antiviral,and metabolic regulatory properties,plays multifunctional roles in apple fruit by enhancing postharvest quality,extending shelf life through oxidative stress reduction,and inhibiting enzymatic browning to preserve color,flavor,and nutritional integrity.Despite the established role of hydroxycinnamoyl transferase(HCT)as a rate-limiting enzyme in CGA biosynthesis,the specific HCT gene responsible for this process and its regulatory mechanisms remain elusive.To address this knowledge gap,we systematically investigated CGA accumulation dynamics during apple storage and functionally characterized MdHCT6,a candidate gene within the HCT family.We found that the chlorogenic acid content in apple fruit increased significantly during postharvest storage compared with the initial storage.Transcriptome analysis showed that the expression level of MdHCT6 was significantly higher than that of other HCT homologues,which was consistent with the reverse transcription quantitative PCR(RT-qPCR)results.In vitro enzymatic assays demonstrated that MdHCT6 catalyzes the synthesis of chlorogenic acid using shikimic acid and quinic acid as precursors,while genetic evidence confirmed its role as a key positive regulator of chlorogenic acid accumulation in apples.Furthermore,we identified the transcription factor MdMYB93 as a direct upstream activator of MdHCT6,establishing a regulatory cascade that governs CGA production.This work not only deciphers the molecular hierarchy of CGA biosynthesis in apples but also provides actionable targets for genetic improvement of antioxidant capacity and postharvest resilience in apple germplasm.
基金supported by the National Natural Science Foundation of China(32373062)the Natural Science Foundation of Shandong Province(ZR2023MC144)Funds of Shandong Province Modern Agricultural Technology System Innovation Team Program(SDAIT-21-10).
文摘Background Deoxynivalenol(DON)is a mycotoxin that severely pollutes feed ingredients,and methods for reducing DON toxicity have become a significant research direction.Chlorogenic acid(CGA)is an active polyphenol found in some plants,which has anti-inflammatory and antioxidant properties and a protective effect on animal intestinal health.The effects of CGA on DON-induced pyroptosis in the intestinal porcine epithelial cell line-J2(IPEC-J2)and its potential mechanism were explored in this study.Results IPEC-J2 cells viability and membrane integrity were inversely correlated with DON concentration.Compared to those in the group treated with DON alone at 2,500 ng/mL,pretreatment with 80μmol/L CGA for 4 h significantly improved cell viability(P<0.01),and the alleviation of typical pyroptotic symptoms induced by DON were observed,including reduced cellular DNA fragmentation,decreased release of lactate dehydrogenase(LDH),normalized ROS levels,restoration of extracellularCa2+andK+contents to normal levels(P<0.01),as well as suppressed the enzyme activities of caspase-1 and caspase-4(P<0.01).Additionally,the mRNA expression levels of TNF,MDP,NOD2,TLR4,ASC and GSDMD were significantly improved(P<0.01),while both mRNA and protein expression levels of NF-κB,NLRP3,caspase-1,IL-1βand IL-18 were significantly upregulated(P<0.01)in the CGA+DON group,compare to those in the DON group.Conclusion Pretreatment with 80μmol/L CGA for 4 h effectively alleviated pyroptosis in IPEC-J2 cells induced by 2,500 ng/mL of DON through inhibiting activation of the NF-κB/NLRP3/capase-1 pathway.
基金supported by the Open Project of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-KF-202201)Tianjin Food Processing Control and Safety Engineering Technology Center(GCZX202303)。
文摘Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.
基金supported by the National Natural Science Foundation of China(81891012,U19A2010,81630101)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202209)+1 种基金Sichuan Province Science and Technology Support Program(2021JDRC0041,2022ZYD0088)Sichuan TCM Science and Technology Industry Innovation Team(2022C001).
文摘Chlorogenic acid(CA)is a natural plant-derived polyphenol compound that is widely present in beverages(coffee and tea),fruits(blueberry,apple,and mulberry),and medicinal plants(Lonicera japonica,Eucommia ulmoides,and Cichorium intybus).In recent years,CA has attracted extensive attention due to its various health benefits,such as anti-inflammatory,immunomodulatory,anti-obesity,anti-diabetes mellitus,and neuroprotection activities.Interestingly,the low bioavailability of CA corresponds to high bioactivity,which raises a key scientifi c question of how low bioavailability CA can achieve high biological activity.In this review,we highlight the gut microbiota as a key target for connecting the two by summarizing a large amount of evidence.Specifi cally,the composition and abundance of gut microbiota,its metabolites,intestinal immunity,barrier function and so on were all changed under different pathological conditions such as infl ammatory bowel disease,liver disease,kidney disease,cardiovascular disease,diabetes mellitus,obesity,etc.Conversely,these changes could be reversed by CA.In a word,CA could achieve pharmacological activity as well as health-protective effects by modulating intestinal immune and barrier function,gut microbiota composition,gut microbiota metabolites,and signaling pathways.This review provides new targets for the prevention and treatment of diseases by CA.Meanwhile,regulating the composition of the gut microbiota through natural products may be a potential strategy to achieve health protection.
基金the National Natural Science Foundation of China,No.82074425Natural Foundation of Hunan Province,No.2023JJ30364 and No.2023JJ30361+1 种基金Hunan Provincial Key R&D Program,No.2023SK2057Key Project of Hunan Provincial Administration of Traditional Chinese Medicine,No.A2023042.
文摘BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a novel ferroptosis inducer or anti-HCC drug.
基金supported by 2003 Nutrition Research Fund of Chinese Nutrition Society
文摘Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.
基金Project (No. 20039902) supported by the Education Committee of Tianjin, China
文摘Flos Lonicerae is a medically useful traditional Chinese medicine herb. However, little is known about the antioxidant properties of Flos Lonicerae extracts. Here the antioxidant capacity of water, methanolic and ethanolic extracts prepared from Flos Lonicerae to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduce Fe3+ to Fe2+ is examined. Chlorogenic acid, a major component of Flos Lonicerae, is identified and further purified from 70% ethanolic extract with high performance liquid chromatography (HPLC) and its antioxidant capacity is characterized. The total phenolic compounds and chlorogenic acid con-tents in Flos Lonicerae are determined. The present results demonstrate that the Flos Lonicerae extracts exhibit antioxidant ac-tivity and chlorogenic acid is a major contributor to this activity.
基金supported by the PAPD(A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions)
文摘The present study was designed to establish and optimize a new method for extracting chlorogenic acid and cynaroside from Lonicera japonica Thunb. through orthogonal experimental designl. A new ultrahigh pressure extraction （UPE） technology was applied to extract chlorogenic acid and cynaroside from L. japonica. The influential factors, including solvent type, ethanol concentration, extraction pressure, time, and temperature, and the solid/liquid ratio, have been studied to optimize the extraction process, The optimal conditions for the UPE were developed by quantitative analysis of the extraction products by HPLC-DAD in comparison with standard samples. In addition, the microstructures of the medicinal materials before and after extraction were studied by scanning electron microscopy （SEM）. Furthermore, the extraction efficiency of different extraction methods and the 2, 2-diphenyl-1-picrylhydrazyl （DPPH） radical scavenging activities of the extracts were investigated. The optimal conditions for extracting chlorogenic acid and cynaroside were as follows： ethanol concentration, 60%; extraction pressure, 400 MPa; extraction time, 2 rain; extraction temperature, 30 ℃; and the solid/liquid ratio, 1 ： 50. Under these conditions, the yields of chlorogenic acid and cynaroside were raised to 4.863% and 0.080%, respectively. Compared with other extraction methods, such as heat reflux extraction （HRE）, ultrasonic extraction （UE）, and Sohxlet extraction （SE）, the UPE method showed several advantages, including higher extraction yield, shorter extraction time, lower energy consumption, and higher purity of the extracts. This study could help better utilize L. japonica flower buds as a readily accessible source of natural antioxidants in food and pharmaceutical industries.
基金supported by the Young and Creative Team for Talent Introduction of Shandong Province(No.10073004)Binzhou Medical University Scientific Research Fund for High-level Talents(Nos.2019KYQD06 and BY2018KYQD11)+1 种基金the Locality-University Cooperation Project of Yantai City(No.2019XDRHXMPT18)the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302)。
文摘Chlorogenic acid(5-CQA),neochlorogenic acid(3-CQA),and cryptochlorogenic acid(4-CQA),usually simultaneously exist in many traditional Chinese medicines(TCMs).However,insufficient attentions have been paid to the comparative metabolism study on these three isomeric constituents with similar effects on anti-inflammation until now.In this study,a novel strategy was established to perform comparative analysis of their metabolic fates in rats and elucidate the pharmacological mechanism of antiinflammation.Firstly,diagnostic product ions(DPIs)deduced from the representative reference standards were adopted to rapidly screen and characterize the metabolites in rat plasma,urine and faeces using UHPLC-Q-TOF MS.Subsequently,Network pharmacology was utilized to elucidate their anti-inflammatory mechanism.Consequently,a total of 73 metabolites were detected and characterized,including 50,47 and 43 metabolites for 5-CQA,4-CQA and 3-CQA,orderly.Moreover,the network pharmacology study indicated that these three isomeric constituents and their major metabolites with similar in vivo metabolic pathways exerted anti-inflammatory effects through co-owned 20 biological processes,which involved 10 major signal pathways and 159 potential targets.Our study shed light on the similarities and differences of the metabolic profiling and anti-inflammatory activity among these three isomeric constituents and set an example for the further researches on the active mechanism of isomeric constituents existing in TCMs based on comparative metabolism study.
基金supported by the National Natural Science foundation of China(No.31071531)the Scientific Research Fund of the Hunan Provincial Education Department(No.14A071)the China National Tobacco Corp Hunan Branch(15-17Aa04)
文摘Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.
基金Project supported by the National Natural Science Foundation of China(No.81322053)the Program for New Century Excellent Talents in University(No.NCET-11-1054)+1 种基金the"Shu Guang"Project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation(No.13SG43)the State Major Science and Technology Special Projects during the 12th Five-Year Plan(No.2012ZX09505001-002),China
文摘Chlorogenic acid（CGA）, a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen（AP）-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase（ALT/AST） in vivo. The effect of CGA on cytochrome P450（CYP） enzymatic（CYP2E1, CYP1A2, and CYP3A4） activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde（MDA）, reactive oxygen species（ROS）, and glutathione（GSH） levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased m RNA expression of peroxiredoxin（Prx） 1, 2, 3, 5, 6, epoxide hydrolase（Ephx） 2, and polymerase（RNA） II（DNA directed） polypeptide K（Polr2k）, and nuclear factor erythroid-2-related factor 2（Nrf2）. In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2 k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.
基金supported by the National Natural Science Foundation of China,No.81971425the Natural Science Foundation of Zhejiang Province,No.LY20H040002(both to XQF).
文摘Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.
基金supported by the National Key Research and Development Program of China(2019YFD1001302 and 2019YFD1001300)National Natural Science Foundation of China(31701483 and 31601382)+2 种基金Jiangsu Agricultural Science and Technology Independent Innovation Fund[CX(19)3063]the National Technical System of Sweetpotato Industry(CARS-10-C3)Jiangsu Province Science and Technology Support Program(BK20171325)。
文摘Sweetpotato[Ipomoea batatas(L.)Lam.],a food crop with both nutritional and medicinal uses,plays essential roles in food security and health-promoting.Chlorogenic acid(CGA),a polyphenol displaying several bioactivities,is distributed in all edible parts of sweetpotato.However,little is known about the specific metabolism of CGA in sweetpotato.In this study,IbPAL1,which encodes an endoplasmic reticulum-localized phenylalanine ammonia lyase(PAL),was isolated and characterized in sweetpotato.CGA accumulation was positively associated with the expression pattern of IbPAL1 in a tissue-specific manner,as further demonstrated by overexpression of IbPAL1.Overexpression of IbPAL1 promoted CGA accumulation and biosynthetic pathway genes expression in leaves,stimulated secondary xylem cell expansion in stems,and inhibited storage root formation.Our results support a potential role for IbPAL1 in sweetpotato CGA biosynthesis and establish a theoretical foundation for detailed mechanism research and nutrient improvement in sweetpotato breeding programs.
基金supported by DRDO,India.The authors are also thankful to the Director,DFRL,and Mysore for providing technical support and valuable suggestions.
文摘In this study,chlorogenic acid(CGA),a phenolic compound widely distributed in fruits and vegetables,was encapsulated into chitosan nanoparticles by ionic gelation method.The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively.A regular,spherical shaped distribution of nanoparticles was observed through scanning electron microscopy(SEM)and the success of entrapment was confirmed by FTIR analysis.The encapsulation efficiency of CGA was at about 59%with the loading efficiency of 5.2%.In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further,the release kinetics study revealed the burst release of 69%CGA from nanoparticles at the end of 100th hours.Pharmacokinetic analysis in rats showed a lower level of Cmax,longer Tmax,longer MRT,larger AUC0et and AUC0e∞for the CGA nanoparticles compared to free CGA.Collectively,these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.
