Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation
Abstract Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury and cardioprotec...
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Nature Portfolio
2016-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/srep27460 |
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| author | Lin-Lin Kang Dong-Mei Zhang Chun-Hua Ma Jian-Hua Zhang Ke-Ke Jia Jia-Hui Liu Rong Wang Ling-Dong Kong |
| author_facet | Lin-Lin Kang Dong-Mei Zhang Chun-Hua Ma Jian-Hua Zhang Ke-Ke Jia Jia-Hui Liu Rong Wang Ling-Dong Kong |
| author_sort | Lin-Lin Kang |
| collection | DOAJ |
| description | Abstract Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis. |
| format | Article |
| id | doaj-art-38665bc273d14ab3a2076a24653745fc |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2016-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-38665bc273d14ab3a2076a24653745fc2024-12-01T12:27:32ZengNature PortfolioScientific Reports2045-23222016-06-016111810.1038/srep27460Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activationLin-Lin Kang0Dong-Mei Zhang1Chun-Hua Ma2Jian-Hua Zhang3Ke-Ke Jia4Jia-Hui Liu5Rong Wang6Ling-Dong Kong7State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing UniversityAbstract Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis.https://doi.org/10.1038/srep27460 |
| spellingShingle | Lin-Lin Kang Dong-Mei Zhang Chun-Hua Ma Jian-Hua Zhang Ke-Ke Jia Jia-Hui Liu Rong Wang Ling-Dong Kong Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation Scientific Reports |
| title | Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation |
| title_full | Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation |
| title_fullStr | Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation |
| title_full_unstemmed | Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation |
| title_short | Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation |
| title_sort | cinnamaldehyde and allopurinol reduce fructose induced cardiac inflammation and fibrosis by attenuating cd36 mediated tlr4 6 irak4 1 signaling to suppress nlrp3 inflammasome activation |
| url | https://doi.org/10.1038/srep27460 |
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