Cichoric Acid Reverses Insulin Resistance and Suppresses Inflammatory Responses in the Glucosamine-Induced HepG2 Cells

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

Data statistics of small RNAs produced by Illumina deep sequencing.

<p>Data statistics of small RNAs produced by Illumina deep sequencing.</p

The occurrence of <i>A</i>. <i>catenella</i> miRNAs that appeared also in other selected species.

<p>Gma: <i>Glycine max</i>, osa: <i>Oryza sativa</i>, ptc: <i>Populus trichocarpa</i>, mdm: <i>Malus domestica</i>, zma: <i>Zea mays</i>, mes: <i>Manihot esculenta</i>, vvi: <i>Vitis vinifera</i>, lus: <i>Linum usitatissimum</i>, aly: <i>Arabidopsis lyrata</i>, nta: <i>Nicotiana tabacum</i>, ath: <i>Arabidopsis thaliana</i>, cme: <i>Cucumis melo</i>, bdi: <i>Brachypodium distachyon</i>, sbi: <i>Sorghum bicolor</i>, mtr: <i>Medicago truncatula</i>, stu: <i>Solanum tuberosum</i>, tcc: <i>Theobroma cacao</i>, rco: <i>Ricinus communis</i>, bna: <i>Brassica napus</i>, ppt: <i>Physcomitrella patens</i>, bra: <i>Brachypodium distachyon</i>, sly: <i>Solanum lycopersicum</i>, cpa: <i>Carica papaya</i>, ghr: <i>Gossypium hirsutum</i>, aqc: <i>Aquilegia caerulea</i>, hvu: <i>Hordeum vulgare</i>, Gma: <i>Glycine max</i>, osa: <i>Oryza sativa</i>, ptc: <i>Populus trichocarpa</i>, mdm: <i>Malus domestica</i>, zma: <i>Zea mays</i>, mes: <i>Manihot esculenta</i>, vvi: <i>Vitis vinifera</i>, lus: <i>Linum usitatissimum</i>, aly: <i>Arabidopsis lyrata</i>, nta: <i>Nicotiana tabacum</i>, ath: <i>Arabidopsis thaliana</i>, cme: <i>Cucumis melo</i>, bdi: <i>Brachypodium distachyon</i>, sbi: <i>Sorghum bicolor</i>, mtr: <i>Medicago truncatula</i>, stu: <i>Solanum tuberosum</i>, tcc: <i>Theobroma cacao</i>, rco: <i>Ricinus communis</i>, bna: <i>Brassica napus</i>, ppt: <i>Physcomitrella patens</i>, bra: <i>Brachypodium distachyon</i>, sly: <i>Solanum lycopersicum</i>, cpa: <i>Carica papaya</i>, ghr: <i>Gossypium hirsutum</i>, aqc: <i>Aquilegia caerulea</i>, hvu: <i>Hordeum vulgare</i>.</p

Novel miRNAs predicted in <i>A</i>. <i>catenella</i>.

<p>Novel miRNAs predicted in <i>A</i>. <i>catenella</i>.</p

miRNA families with more than two members.

<p>miRNA families with more than two members.</p

Venn diagram of identified known miRNAs in the two libraries.

<p>The diagram not only shows the numbers of miRNA that were expressed in the lag phase and the logarithmic phase preferentially but also the co-expressed miRNAs in both phases.</p

Partial gene ontology (GO) classification annotated for predicted target genes of 12 differentially expressed miRNAs.

<p>The figure shows partial GO enrichment of the 1813 predicted target genes in three GO ontologies: biological processes, cellular component and molecular function.</p

qPCR validation of the differentially expressedaca-miR-3p-456915.

<p>Normalized expression level (2^–ΔΔCT) of tae-miR159a and aca-miR-3p-456915 under different growth phases and conditions.</p

The significantly enriched KEGG pathways of target genes for 12 differentially expressed miRNAs.

<p>The significantly enriched KEGG pathways of target genes for 12 differentially expressed miRNAs.</p

First nucleotide bias of known miRNAs in <i>A</i>. <i>catenella</i>.

<p>The figure indicates the first nucleotide of 18–25 nt miRNAs. U had the greatest frequency among miRNAs of 20–23 nt.</p