Ferulic Acid and P-Coumaric Acid Synergistically Attenuate Non-Alcoholic Fatty Liver Disease through HDAC1/PPARG-Mediated Free Fatty Acid Uptake
Abstract
:1. Introduction
2. Results
2.1. Prediction of the Association of FA/p-CA with Non-alcoholic Fatty Liver Disease
2.2. FA/p-CA Treatment Suppresses FFA-Induced Lipid Accumulation In Vitro
2.3. FA/p-CA Attenuate HFD-Induced Hepatic Injury and Steatosis In Vivo
2.4. The Potential Pathways of FA p-CA Targets
2.5. HDAC1 Is Involved in Amelioration of NAFLD by FA/p-CA
2.6. FA/p-CA Inhibit Hepatic Lipid Uptake Via the HDAC1/PPARG Axis
3. Discussion
4. Martials and Methods
4.1. Materials
4.2. Cell Culture and Steatosis Induction
4.3. Bodipy and Oil Red O Staining
4.4. Triglyceride Assay
4.5. Mice Experiment
4.6. Histological Examinations
4.7. Western Blot
4.8. Quantitative RT-PCR
4.9. Molecular Docking
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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MCODE | GO | Description | Log10(P) |
---|---|---|---|
MCODE_1 | R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | −14.9 |
R-HSA-190872 | Transport of connexons to the plasma membrane | −14.7 | |
R-HSA-389977 | Post-chaperonin tubulin folding pathway | −14.3 | |
MCODE_2 | GO:1901615 | organic hydroxy compound metabolic process | −12.7 |
hsa00350 | Tyrosine metabolism | −10.4 | |
GO:0010817 | regulation of hormone levels | −9.1 | |
MCODE_3 | M207 | PID RETINOIC ACID PATHWAY | −19.3 |
R-HSA-383280 | Nuclear Receptor transcription pathway | −17.5 | |
M162 | PID RXR VDR PATHWAY | −16.3 | |
MCODE_4 | WP167 | Eicosanoid synthesis | −16.6 |
WP5122 | Prostaglandin and leukotriene metabolism in senescence | −16.2 | |
GO:0019369 | arachidonic acid metabolic process | −14.5 | |
MCODE_5 | R-HSA-211859 | Biological oxidations | −17.1 |
WP702 | Metapathway biotransformation Phase I and II | −14.6 | |
R-HSA-156580 | Phase II—Conjugation of compounds | −13.3 | |
MCODE_6 | hsa05130 | Pathogenic Escherichia coli infection | −13.1 |
hsa05417 | Lipid and atherosclerosis | −12.9 | |
hsa05131 | Shigellosis | −12.6 | |
MCODE_7 | M186 | PID PDGFRB PATHWAY | −6.1 |
R-HSA-1280215 | Cytokine Signaling in Immune system | −5.8 | |
GO:0030100 | regulation of endocytosis | −5.5 | |
MCODE_8 | WP272 | Blood clotting cascade | −8.8 |
WP558 | Complement and coagulation cascades | −7.5 | |
GO:0030193 | regulation of blood coagulation | −7.4 | |
MCODE_9 | WP702 | Metapathway biotransformation Phase I and II | −6.6 |
MCODE | GO | Description | Log10(P) |
---|---|---|---|
MCODE_1 | R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | −27.4 |
R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | −26.5 | |
R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | −26.5 | |
MCODE_2 | R-HSA-1592389 | Activation of Matrix Metalloproteinases | −7 |
M174 | PID UPA UPAR PATHWAY | −6.7 | |
WP534 | Glycolysis and gluconeogenesis | −6.6 | |
MCODE_3 | GO:0046394 | carboxylic acid biosynthetic process | −6.4 |
GO:0016053 | organic acid biosynthetic process | −6.4 | |
GO:1901607 | alpha-amino acid biosynthetic process | −6.2 | |
MCODE_4 | R-HSA-418594 | G alpha (i) signaling events | −11.9 |
R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | −11.8 | |
R-HSA-500792 | GPCR ligand binding | −10.9 | |
MCODE_6 | R-HSA-6798695 | Neutrophil degranulation | −7.2 |
R-HSA-1474244 | Extracellular matrix organization | −5.4 | |
MCODE_7 | hsa00982 | Drug metabolism—cytochrome P450 | −10.5 |
hsa00980 | Metabolism of xenobiotics by cytochrome P450 | −10.4 | |
R-HSA-211859 | Biological oxidations | −8.5 | |
MCODE_8 | R-HSA-383280 | Nuclear receptor transcription pathway | −8.3 |
MCODE_9 | WP702 | Metapathway biotransformation Phase I and II | −6.6 |
MCODE_11 | R-HSA-6798695 | Neutrophil degranulation | −5.4 |
Genes | Sequences (5′-3′) | |
---|---|---|
FABP | forward primer: | reverse primer: |
TGGCGTTTGACAGCACTTGG | AGCTTCAAATTGTCATGAGCTGCA | |
CD36 | forward primer: | reverse primer: |
TCTCAATCTGGCTGTGGCAG | CAGGGTACGGAACCAAACTCA | |
GAPDH | forward primer: | reverse primer: |
GCACCGTCAAGGCTGAGAAC | TGGTGAAGAACGCCAGTGGA |
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Cui, K.; Zhang, L.; La, X.; Wu, H.; Yang, R.; Li, H.; Li, Z. Ferulic Acid and P-Coumaric Acid Synergistically Attenuate Non-Alcoholic Fatty Liver Disease through HDAC1/PPARG-Mediated Free Fatty Acid Uptake. Int. J. Mol. Sci. 2022, 23, 15297. https://doi.org/10.3390/ijms232315297
Cui K, Zhang L, La X, Wu H, Yang R, Li H, Li Z. Ferulic Acid and P-Coumaric Acid Synergistically Attenuate Non-Alcoholic Fatty Liver Disease through HDAC1/PPARG-Mediated Free Fatty Acid Uptake. International Journal of Molecular Sciences. 2022; 23(23):15297. https://doi.org/10.3390/ijms232315297
Chicago/Turabian StyleCui, Kaili, Lichao Zhang, Xiaoqin La, Haili Wu, Ruipeng Yang, Hanqing Li, and Zhuoyu Li. 2022. "Ferulic Acid and P-Coumaric Acid Synergistically Attenuate Non-Alcoholic Fatty Liver Disease through HDAC1/PPARG-Mediated Free Fatty Acid Uptake" International Journal of Molecular Sciences 23, no. 23: 15297. https://doi.org/10.3390/ijms232315297