Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Solution
2.2. Network Pharmacology
2.3. Cell Culture and Treatment
2.4. Zebrafish Body Size Measurements
2.5. Maintenance of Zebrafish and Treatment
2.6. Oil Red Staining and Histopathology
2.7. Fluorescent Staining and Quantification
2.8. Biochemical Measurement
2.9. RT-qPCR
2.10. Statistical Analysis
3. Results
3.1. Effect of K3O on Body Size on HCD-induced Larval Zebrafish
3.2. Lipid Metabolism Treatment Effect of K3O on HCD-induced Larval Zebrafish
3.3. Oxidation Stress Treatment Effect of K3O on HCD-induced Larval Zebrafish
3.4. Inflammation Treatment Effect of K3O on HCD-induced Larval Zebrafish
3.5. Mechanism of K3O in Multiregulations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Friedman, S.L.; Neuschwander-Tetri, B.A.; Mary, R.; Sanyal, A.J. Mechanisms of NAFLD development and therapeutic strat-egies. Nat. Med. 2018.
- Younossi, Z.; Stepanova, M.; Ong, J.; Trimble, G.; AlQahtani, S.; Younossi, I.; Ahmed, A.; Racila, A.; Henry, L. Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States. Clin. Gastroenterol. Hepatol. : Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2021, 19, 580–589e5. [Google Scholar] [CrossRef]
- Younossi, Z.; Anstee, Q.; Marietti, M.; Hardy, T.; Henry, L.; Eslam, M.; George, J.; Bugianesi, E. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 11–20. [Google Scholar] [CrossRef] [PubMed]
- Mlala, S.; Oyedeji, A.O.; Gondwe, M.; Oyedeji, O.O. molecules Ursolic Acid and Its Derivatives as Bioactive Agents. Molecules 2019, 24, 2751. [Google Scholar] [CrossRef] [Green Version]
- Shang, X.; Tan, J.N.; Du, Y.; Liu, X.; Zhang, Z. Environmentally-Friendly Extraction of Flavonoids from Cyclocarya paliurus (Batal). Iljinskaja Leaves with Deep Eutectic Solvents and Evaluation of Their Antioxidant Activities. Molecules 2018, 23, 2110. [Google Scholar]
- Yang, L.; Cao, Y.; Fang, S.; Wang, T.; Yin, Z.; Shang, X.; Yang, W.; Fu, X. Antidiabetic Effect of Cyclocarya paliurus Leaves Depends on the Contents of Antihyperglycemic Flavonoids and Antihyperlipidemic Triterpenoids. Molecules 2018, 23, 1042. [Google Scholar]
- Cano, A.; Arnao, M.; Williamson, G.; Garcia-Conesa, M. Superoxide scavenging by polyphenols: Effect of conjugation and dimerization. Redox Rep. Commun. Free Radic. Res. 2002, 7, 379–383. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Chen, P.; Tang, C.; Wang, Y.; Li, Y.; Zhang, H. Antinociceptive and anti-inflammatory activities of extract and two isolated flavonoids of Carthamus tinctorius L. J. Ethnopharmacol. 2014, 151, 944–950. [Google Scholar] [CrossRef]
- Liao, L.; Li, S.; Ping, L. Simultaneous determination of seven triterpenoids and triterpenoid saponins in Folium llicis Purpureae by high performance liquid chromatography coupled with evaporative light scattering detection. J. Sep. Ence 2015, 28, 2061–2066. [Google Scholar]
- Youn, H.J.; Kim, K.B.; Han, H.S.; An, I.S.; Ahn, K.J. 23-Hydroxytormentic acid protects human dermal fibroblasts by attenuating UVA-induced oxidative stress. Photodermatol. Photoimmunol. Photomed. 2017, 33, 92–100. [Google Scholar] [CrossRef] [PubMed]
- Ma, X.; Chen, G.; Wang, J.; Xu, J.; Zhao, F.; Hu, M.; Xu, Z.; Yang, B.; Guo, J.; Sun, S.; et al. Pedunculoside attenuates pathological phenotypes of fibroblast-like synoviocytes and protects against collagen-induced arthritis. Scand. J. Rheumatol. 2019, 48, 383–392. [Google Scholar] [CrossRef]
- Kibble, M.; Saarinen, N.; Tang, J.; Wennerberg, K.; Mäkelä, S.; Aittokallio, T. Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat. Prod. Rep. 2015, 32, 1249–1266. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, S.; Bhattacharjee, P.; Kar, A.; Mukherjee, P. LC-MS/MS analysis and network pharmacology of Trigonella foe-num-graecum—A plant from Ayurveda against hyperlipidemia and hyperglycemia with combination synergy. Phytomed. Int. J. Phytother. Phytopharm. 2019, 60, 152944. [Google Scholar]
- Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 2014, 6, 13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jackson, S.; Darbousset, R.; Schoenwaelder, S. Thromboinflammation: Challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood 2019, 133, 906–918. [Google Scholar] [CrossRef] [Green Version]
- Chen, X.; Wang, R.; Chen, W.; Lai, L.; Li, Z. Decoy receptor-3 regulates inflammation and apoptosis via PI3K/AKT signaling pathway in coronary heart disease. Exp. Ther. Med. 2019, 17, 2614–2622. [Google Scholar] [CrossRef] [Green Version]
- Sauaia, A.; Moore, F.A.; Moore, E.E. Postinjury Inflammation and Organ Dysfunction. Crit. Care Clin. 2017, 33, 167–191. [Google Scholar] [CrossRef] [Green Version]
- Lim, J.S.; Mietus-Snyder, M.; Valente, A.; Schwarz, J.M.; Lustig, R.H. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat. Rev. Gastroenterol. Hepatol. 2010, 7, 251–264. [Google Scholar] [CrossRef] [PubMed]
- Michal; Pawlak; Philippe; Lefebvre; Bart; Staels, Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 2015, 62, 720–733. [CrossRef] [Green Version]
- Romero-Gómez, M.; Zelber-Sagi, S.; Trenell, M. Treatment of NAFLD with diet, physical activity and exercise. J. Hepatol. 2017, 829. [Google Scholar] [CrossRef] [Green Version]
- Schuster, S.; Cabrera, D.; Arrese, M.; Feldstein, A.E. Triggering and resolution of inflammation in NASH. Nat. Rev. Gastroenterol. Hepatol 2018, 15 (Suppl. 1), 349–364. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Zhou, J.; Liu, Q.Z.; Wang, L.L.; Shang, J. Simvastatin and Bezafibrate ameliorate Emotional disorder Induced by High fat diet in C57BL/6 mice. Sci. Rep. 2017, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Musso, G.; Gambino, R.; Cassader, M. Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis. Prog. Lipid Res. 2013, 52, 175–191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tirosh, O. Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression. Oxidative Med. Cell. Longev. 2018, 2018, 2548154. [Google Scholar] [CrossRef] [PubMed]
- Luo, H.; Li, Q.; Wu, N.; Shen, Y.; Liao, W.; Yang, Y.; Dong, E.; Zhang, G.; Liu, B.; Yue, X.; et al. Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish. Atherosclerosis 2019, 290, 125–135. [Google Scholar] [CrossRef] [PubMed]
- Xie, Z.; Charles, M.; Fan, J.; Charlebois, D.; Khanizadeh, S.; Rolland, D.; Roussel, D.; Deschênes, M.; Dubé, C. Effects of preharvest ultraviolet-C irradiation on fruit phytochemical profiles and antioxidant capacity in three strawberry (Fragaria × ananassa Duch) cultivars. J. Sci. Food Agric. 2015, 95, 2996–3002. [Google Scholar] [CrossRef]
- Qha, C.; Mk, B.; Zx, A.; Jing, Y.; Lz, A.; Hme, B.; Ct, B.; Hc, A.; Jg, A.; Mjl, A. Inhibition of the Keap1-Nrf2 protein-protein interaction protects retinal cells and ameliorates retinal ischemia-reperfusion injury. Free Radic. Biol. Med. 2020, 146, 181–188. [Google Scholar]
- Orrù, C.; Perra, A.; Kowalik, M.A.; Rizzolio, S.; Columbano, A. Distinct Mechanisms Are Responsible for Nrf2-Keap1 Pathway Activation at Different Stages of Rat Hepatocarcinogenesis. Cancers 2020, 12, 2305. [Google Scholar] [CrossRef]
- Kim, S.; Viswanath, A.; Park, J.H.; Lee, H.E.; Park, K.D. Nrf2 activator via interference of Nrf2-Keap1 interaction has antioxidant and anti-inflammatory properties in Parkinson’s disease animal model. Neuropharmacology 2020, 167, 107989. [Google Scholar] [CrossRef]
- Kopacz, A.; Kloska, D.; Forman, H.J.; Jozkowicz, A.; Grochot-Przeczek, A. Beyond repression of Nrf2: An update on Keap1. Free Radic. Biol. Med. 2020, 157. [Google Scholar] [CrossRef]
- Lima, A.; Cha, B.; Amin, J.; Smith, L.; Anderson, B. Zebrafish embryo model of Bartonella henselae infection. Zebrafish 2014, 11, 434–446. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yuan, X.; Huang, L.; Lei, J.; Long, Y.; Li, C. Study on Anti-Inflammatory Effect and Major Anti-Inflammatory Components of PSORI-CM02 by Zebrafish Model. Evid. Based Complement. Altern. Med. 2020, 2020, 1–10. [Google Scholar] [CrossRef]
- Lee, M.R.; Lee, H.Y.; Lee, G.H.; Kim, H.K.; Chae, H.J. Ixeris dentata Decreases ER Stress and Hepatic Lipid Accumulation through Regulation of ApoB Secretion. Am. J. Chin. Med. 2014, 42, 639–649. [Google Scholar] [CrossRef] [PubMed]
- Lawlor, D.A.; Mark, C.; Corrie, M.W.; Emma, A.; Abigail, F.; Howe, L.D.; Chris, D.; Naveed, S. Nonalcoholic fatty liver disease, liver fibrosis, and cardiometabolic risk factors in adolescence: A cross-sectional study of 1874 general population adolescents. J. Clin. Endocrinol. Metab. 2014, 99, 410–417. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qiu, T.; Pei, P.; Yao, X.; Jiang, L.; Wei, S.; Wang, Z.; Bai, J.; Yang, G.; Gao, N.; Yang, L.; et al. Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway. Cell Death Dis. 2018, 9, 946. [Google Scholar] [CrossRef] [Green Version]
- Zhong, X.; Liu, H. Baicalin attenuates diet induced nonalcoholic steatohepatitis by inhibiting inflammation and oxidative stress via suppressing JNK signaling pathways. Biomed. Pharmacother. Biomed. Pharmacother. 2018, 98, 111–117. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, J. Systems Biology of Metabolism: A Driver for Developing Personalized and Precision Medicine. Cell Metab. 2017, 25, 572–579. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, B.; Chen, J.; Jiang, Q.; Wang, X.; Lu, Y.; Gong, L.; Chen, D. Simultaneous determination of three active components in rat plasma by uplc-ms/ms: Ap-plication to pharmacokinetic study after oral administration of herba sarcandrae extract. Biomed. Chromatogr. 2017, 31, 101002/bmc3834. [Google Scholar] [CrossRef]
- Liu, Y.; Chen, P.; Zhou, M.; Wang, T.; Fang, S.; Shang, X.; Fu, X. Geographic Variation in the Chemical Composition and Antioxidant Properties of Phenolic Compounds from Cyclocarya paliurus (Batal) Iljinskaja Leaves. Molecules 2018, 23, 2440. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Gene Name | Species | Forward Primer (5′ -> 3′) | Reverse Primer (5′ -> 3′) |
---|---|---|---|
serbf1 | Danio rerio | CATCCACATGGCTCTGAGTG | CTCATCCACAAAGAAGCGGT |
fasn pparb cpt1a pparg mmp9 tgfb1 keap1 nrf2 il1b tnfa | Danio rerio Danio rerio Danio rerio Danio rerio Danio rerio Danio rerio Danio rerio Danio rerio Danio rerio Danio rerio | ATCTGTTCCTGTTCGATGGC CGTCGTCAGGTGTTTACGGT ACTCTCGATGGACCCTGTGA CTGCCGCATACACAAGAAGA GAAGCGTTACGGCTACGT CATAAGAGCCACAGACAGAAG CCAACGGCATAGAGGTAGTTAT TTGTCTTTGGTGAACGGAGGT TGGCGAACGTCATCCAAG GCTTATGAGCCATGCAGTGA | AGCATATCTCGGCTGACGTT AGGCACTTCTGGAATCGACA CTGGATGAAGGCATCTGGAC TCACGTCACTGGAGAACTCG TTCCATGTCTGGCGAATAG GTAGAGCGAGCGTAAACAG CCTGTATGTGGTAGGAGGGTT CTCGGAGGAGATGGAAGGAAG GGAGCACTGGGCGACGCATA TGCCCAGTCTGTCTCCTTCT |
il6 | Danio rerio | AGACCGCTGCCTGTCTAAAA | TTTGATGTCGTTCACCAGGA |
Nrf2 | Homo sapiens | ACCTCCCTGTTGTTGACTT | CACTTTATTCTTACCCCTCCT |
Keap1 | Homo sapiens | TTACGACCCAGATACAGACA | TGCCCAAGAAACAAAAGT |
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Deng, Y.; Ma, J.; Weng, X.; Wang, Y.; Li, M.; Yang, T.; Dou, Z.; Yin, Z.; Shang, J. Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress. Life 2021, 11, 445. https://doi.org/10.3390/life11050445
Deng Y, Ma J, Weng X, Wang Y, Li M, Yang T, Dou Z, Yin Z, Shang J. Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress. Life. 2021; 11(5):445. https://doi.org/10.3390/life11050445
Chicago/Turabian StyleDeng, Yang, Ji Ma, Xin Weng, Yuqin Wang, Maoru Li, Tingting Yang, Zhiyang Dou, Zhiqi Yin, and Jing Shang. 2021. "Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress" Life 11, no. 5: 445. https://doi.org/10.3390/life11050445