Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway
Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic...
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| Format: | Article |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00850/full |
| _version_ | 1818543481205817344 |
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| author | Zhuo Chen Xiang Gao Yang Jiao Yu Qiu Anlu Wang Meili Yu Fangyuan Che Siming Li Jing Liu Jingen Li He Zhang Changan Yu Geng Li Yanxiang Gao Lin Pan Weiliang Sun Jing Guo Bingyan Cao Yilin Zhu Hao Xu |
| author_facet | Zhuo Chen Xiang Gao Yang Jiao Yu Qiu Anlu Wang Meili Yu Fangyuan Che Siming Li Jing Liu Jingen Li He Zhang Changan Yu Geng Li Yanxiang Gao Lin Pan Weiliang Sun Jing Guo Bingyan Cao Yilin Zhu Hao Xu |
| author_sort | Zhuo Chen |
| collection | DOAJ |
| description | Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-deficient (ApoE−/−) mice.Methods: Male ApoE−/− mice (6 weeks) were fed with a high-fat diet for 13 weeks and then randomized to the model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or the atorvastatin group (5 mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber, and foam cells to the plaque. The expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum levels of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array.Results: Tan IIA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15 ± 1.2%, HT: 12.2 ± 1.64%, MT: 13.93 ± 1.59%, MOD: 18.84 ± 1.46%, P < 0.05) or foam cells (ATO: 16.05 ± 1.26%, HT: 14.88 ± 1.79%, MT: 16.61 ± 1.47%, MOD: 22.08 ± 1.69%, P < 0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22 ± 1.91%, HT: 17.58 ± 1.33%, MT: 15.71 ± 2.26%, LT:14.92 ± 1.65%, MOD: 9.61 ± 0.7%, P < 0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88, and NF-κB p65, and serum level of MCP-1 and TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL, or TG levels between ApoE–/– mice and those treated with atorvastatin.Conclusions: These results suggest that Tan IIA could stabilize vulnerable AS plaque in ApoE−/− mice, and this anti-inflammatory and immune-regulating effect may be achieved via the TLR4/MyD88/NF-κB signaling pathway. |
| first_indexed | 2024-12-11T22:35:57Z |
| format | Article |
| id | doaj.art-428bd89da96b4939b4fb922b61a450e6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T22:35:57Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-428bd89da96b4939b4fb922b61a450e62022-12-22T00:47:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-07-011010.3389/fphar.2019.00850450623Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal PathwayZhuo Chen0Xiang Gao1Yang Jiao2Yu Qiu3Anlu Wang4Meili Yu5Fangyuan Che6Siming Li7Jing Liu8Jingen Li9He Zhang10Changan Yu11Geng Li12Yanxiang Gao13Lin Pan14Weiliang Sun15Jing Guo16Bingyan Cao17Yilin Zhu18Hao Xu19Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInternal medicine, Tieying Hospital of Fengtai District, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, Beijing, ChinaBeijing First Hospital of Integrated Chinese and Western Medicine, Beijing, ChinaCardiovascular Department, Beijing hospital of Traditional Chinese Medicine Shunyi branch, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGraduate school, China Academy of Chinese Medical, Beijing, ChinaDongzhimen Hospital, The First Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, Beijing, ChinaChina-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaWangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBackground: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-deficient (ApoE−/−) mice.Methods: Male ApoE−/− mice (6 weeks) were fed with a high-fat diet for 13 weeks and then randomized to the model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or the atorvastatin group (5 mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber, and foam cells to the plaque. The expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum levels of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array.Results: Tan IIA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15 ± 1.2%, HT: 12.2 ± 1.64%, MT: 13.93 ± 1.59%, MOD: 18.84 ± 1.46%, P < 0.05) or foam cells (ATO: 16.05 ± 1.26%, HT: 14.88 ± 1.79%, MT: 16.61 ± 1.47%, MOD: 22.08 ± 1.69%, P < 0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22 ± 1.91%, HT: 17.58 ± 1.33%, MT: 15.71 ± 2.26%, LT:14.92 ± 1.65%, MOD: 9.61 ± 0.7%, P < 0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88, and NF-κB p65, and serum level of MCP-1 and TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL, or TG levels between ApoE–/– mice and those treated with atorvastatin.Conclusions: These results suggest that Tan IIA could stabilize vulnerable AS plaque in ApoE−/− mice, and this anti-inflammatory and immune-regulating effect may be achieved via the TLR4/MyD88/NF-κB signaling pathway.https://www.frontiersin.org/article/10.3389/fphar.2019.00850/fullTanshinone IIAatherosclerosisanti-inflammatoryimmune regulationTLR4/MyD88/NF-κB |
| spellingShingle | Zhuo Chen Xiang Gao Yang Jiao Yu Qiu Anlu Wang Meili Yu Fangyuan Che Siming Li Jing Liu Jingen Li He Zhang Changan Yu Geng Li Yanxiang Gao Lin Pan Weiliang Sun Jing Guo Bingyan Cao Yilin Zhu Hao Xu Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway Frontiers in Pharmacology Tanshinone IIA atherosclerosis anti-inflammatory immune regulation TLR4/MyD88/NF-κB |
| title | Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway |
| title_full | Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway |
| title_fullStr | Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway |
| title_full_unstemmed | Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway |
| title_short | Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway |
| title_sort | tanshinone iia exerts anti inflammatory and immune regulating effects on vulnerable atherosclerotic plaque partially via the tlr4 myd88 nf κb signal pathway |
| topic | Tanshinone IIA atherosclerosis anti-inflammatory immune regulation TLR4/MyD88/NF-κB |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00850/full |
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