New Role of Hispidulin in Lipid Metabolism: PPARα Activator

Wu, Xinchi; Xu, Juan

doi:10.1007/s11745-016-4200-7

Cited by 19 publications

(11 citation statements)

References 40 publications

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“…Moreover, higher fat content in the tail than in visceral in Tan sheep breed is attributed to down-regulation of this gene 16 . EHHADH encodes a bifunctional β-oxidation enzyme involved in the peroxisomal fatty acid oxidation 68 . ACSL1 prepares long-chain fatty acids for oxidation through addition of co-enzyme A 69 .…”

Section: Discussionmentioning

confidence: 99%

Deep transcriptome analysis using RNA-Seq suggests novel insights into molecular aspects of fat-tail metabolism in sheep

Bakhtiarizadeh

Salehi

Alamouti

et al. 2019

Sci Rep

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Fat-tail content of sheep breeds is varied and the molecular mechanisms regulating fat-tail development have not been well characterized. Aiming at better identifying the important candidate genes and their functional pathways contributing to fat deposition in the tail, a comparative transcriptome analysis was performed between fat- (Lori-Bakhtiari) and thin-tailed (Zel) Iranian sheep breeds using RNA-seq. The experiment was conducted on six male lambs (three lambs per each breed) at seven months of age. Four different combinations of aligners and statistical methods including Hisat2 + edgeR, Hisat2 + DESeq2, STAR + edgeR and STAR + DESeq2 were used to identify the differentially expressed genes (DEGs). The DEGs were selected for functional enrichment analysis and protein-protein interaction (PPI) network construction. Module analysis was also conducted to mine the functional sub-networks from the PPI network. In total, 264 genes including 80 up- and 184 down-regulated genes were identified as DEGs. The RNA-Seq results were validated by Q-RT-PCR. Functional analysis of DEGs and the module analysis of PPI network demonstrated that in addition to pathways affecting lipid metabolism, a series of enriched functional terms related to “response to interleukin”, “MAPK signaling pathways”, “Wnt signaling pathway”, “ECM-receptor interaction”, “regulation of actin cytoskeleton”, and “response to cAMP” might contribute to the deposition of fat in tails of sheep. Overall results using RNA-Seq analysis characterized important candidate genes involved in the fatty acid metabolism and regulation of fat deposition, suggesting novel insights into molecular aspects of fat-tail metabolism in sheep. Selected DEGs should be further investigated as potential markers associated with the fat-tail development in sheep breeds.

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Section: Discussionmentioning

confidence: 99%

Deep transcriptome analysis using RNA-Seq suggests novel insights into molecular aspects of fat-tail metabolism in sheep

Bakhtiarizadeh

Salehi

Alamouti

et al. 2019

Sci Rep

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“…Second, hispidulin modulates lipid metabolism. Hispidulin directly binds to PPAR-α, and then modulates expression of lipid metabolism enzymes (fatty acid binding protein 1/2, and long chain acyl-CoA synthetase 1) [20]. Recently, it was also reported that hispidulin inhibits adipogenesis via inhibition of PPAR-γ expression [21].…”

Section: Discussionmentioning

confidence: 99%

Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines

et al. 2019

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Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and β-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.

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“…In vivo data suggested that 3-month treatment with hispidulin or fenofibrate in dyslipidaemic rat improved the lipid profile 59 . The related flavone wogonin ( 42 ), commonly extracted from the traditional Chinese medicine Scutellaria baicalensis, showed a somewhat similar pharmacological profile.…”

Section: Natural Products Modulating Pparαmentioning

confidence: 99%

The potential of natural products for targeting PPAR α

Rigano

Sirignano

Taglialatela‐Scafati

2017

Acta Pharmaceutica Sinica B

128

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Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.

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New Role of Hispidulin in Lipid Metabolism: PPARα Activator

Cited by 19 publications

References 40 publications

Deep transcriptome analysis using RNA-Seq suggests novel insights into molecular aspects of fat-tail metabolism in sheep

Deep transcriptome analysis using RNA-Seq suggests novel insights into molecular aspects of fat-tail metabolism in sheep

Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines

The potential of natural products for targeting PPAR α

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