Tribulus terrestris L. extract ameliorates atherosclerosis by inhibition of vascular smooth muscle cell proliferation in ApoE(-/-) mice and A7r5 cells via suppression of Akt/MEK/ERK signaling
文献类型：期刊论文
| 作者 | Zhang, Jing2; Zhao, Wai-Rong2; Shi, Wen-Ting2; Tan, Jun-Jie1 ; Zhang, Kai-Yu2; Tang, Jing-Yi2; Chen, Xin-Lin2; Zhou, Zhong-Yan2
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| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
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| 出版日期 | 2022-10-28 |
| 卷号 | 297页码:15 |
| ISSN号 | 0378-8741 |
| 关键词 | Plaque progression Hyperlipidemia Mitogen-activated protein kinases Oxidized low density lipoprotein VSMC phenotype Switching |
| DOI | 10.1016/j.jep.2022.115547 |
| 通讯作者 | Chen, Xin-Lin(heal7374@163.com) ; Zhou, Zhong-Yan(biozzy@126.com) |
| 英文摘要 | Ethnopharmacological relevance: Atherosclerosis (AS) is one of major threatens of death worldwide, and vascular smooth muscle cell (VSMC) proliferation is an important characteristic in the progression of AS. Tribulus terrestris L. is a well-known Chinese Materia Medica for treating skin pruritus, vertigo and cardiovascular diseases in traditional Chinese medicine. However, its anti-AS activity and inhibition effect on VSMC proliferation are not fully elucidated. Aims: We hypothesize that the furostanol saponins enriched extract (FSEE) of T. terrestris L. presents anti-AS effect by inhibition of VSMC proliferation. The molecular action mechanism underlying the anti-VSMC proliferation effect of FSEE is also investigated. Materials and methods: Apolipoprotein-E deficient (ApoE(-/-)) mice and rat thoracic smooth muscle cell A7r5 were employed as the in vivo and in vitro models respectively to evaluate the anti- AS and VSMC proliferation effects of FSEE. In ApoE(-/-) mice, the amounts of total cholesterol, triglyceride, low density lipoprotein and high density lipoprotein in serum were measured by commercially available kits. The size of atherosclerotic plaque was observed by hematoxylin & eosin staining. The protein expressions of a-smooth muscle actin (alpha-SMA) and osteopontin (OPN) in the plaque were examined by immunohistochemistry. In A7r5 cells, the cell viability and proliferation were tested by MTT and Real Time Cell Analysis assays. The cell migration was evaluated by wound healing assay. Propidium iodide staining followed by flow cytometry was used to analyze the cell cycle progression. The expression of intracellular total and phosphorylated proteins including protein kinase B (Akt) and mitogen-activated protein kinases (MAPKs), such as mitogen-activated extracellular signal-regulated kinase (MEK), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), were detected by western blotting analysis. Results: FSEE significantly reduced the area of atherosclerotic plaque in high-fat diet-fed ApoE(-/-) mice. And FSEE increased the protein expression level of a-SMA and decreased the level of OPN in atherosclerotic plaque, which revealed the inhibition of VSMC phenotype switching and proliferation. In A7r5 cells, FSEE suppressed fetal bovine serum (FBS) or oxidized low density lipoprotein (oxLDL)-triggered VSMC proliferation and migration in a concentration dependent manner. FSEE protected against the elevation of cell numbers in S phase induced by FBS or oxLDL and the reduction of cell numbers in G0/G1 phase induced by oxLDL. Moreover, the phosphorylation of Akt and MAPKs including MEK, ERK and JNK could be facilitated by FBS or oxLDL, while cotreatment of FSEE attenuated the phosphorylation of Akt induced by oxLDL as well as the phosphorylation of MEK and ERK induced by FBS. In addition, (25R)-terrestrinin B (JL-6), which was the main ingredient of FSEE, and its potential active pharmaceutical ingredients tigogenin (Tigo) and hecogenin (Heco) also significantly attenuated FBS or oxLDL-induced VSMC proliferation in A7r5 cells. Conclusion: FSEE presents potent anti- AS and VSMC proliferation activities and the underlying mechanism is likely to the suppression of Akt/MEK/ERK signaling. The active components of FSEE are JL-6 and its potential active pharmaceutical ingredients Tigo and Heco. So, FSEE and its active compounds may be potential therapeutic drug candidates for AS. |
| WOS关键词 | NEOINTIMAL HYPERPLASIA ; LIPID PROFILE ; APOE-KNOCKOUT ; MECHANISMS ; MIGRATION ; SAPONINS ; GLUCOSE ; RATS ; P38 |
| 资助项目 | Shanghai Municipal Health Commission[2020JP019] ; Shanghai Municipal Health Commission[GWIV-28] ; National Natural Science Foundation of China[82074371] ; Longhua hospital, Shanghai University of Traditional Chinese Medicine[YM2021017] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| 出版者 | ELSEVIER IRELAND LTD |
| WOS记录号 | WOS:000885401200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304674]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Xin-Lin; Zhou, Zhong-Yan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Medica, Shanghai, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Jing,Zhao, Wai-Rong,Shi, Wen-Ting,et al. Tribulus terrestris L. extract ameliorates atherosclerosis by inhibition of vascular smooth muscle cell proliferation in ApoE(-/-) mice and A7r5 cells via suppression of Akt/MEK/ERK signaling[J]. JOURNAL OF ETHNOPHARMACOLOGY,2022,297:15. |
| APA | Zhang, Jing.,Zhao, Wai-Rong.,Shi, Wen-Ting.,Tan, Jun-Jie.,Zhang, Kai-Yu.,...&Zhou, Zhong-Yan.(2022).Tribulus terrestris L. extract ameliorates atherosclerosis by inhibition of vascular smooth muscle cell proliferation in ApoE(-/-) mice and A7r5 cells via suppression of Akt/MEK/ERK signaling.JOURNAL OF ETHNOPHARMACOLOGY,297,15. |
| MLA | Zhang, Jing,et al."Tribulus terrestris L. extract ameliorates atherosclerosis by inhibition of vascular smooth muscle cell proliferation in ApoE(-/-) mice and A7r5 cells via suppression of Akt/MEK/ERK signaling".JOURNAL OF ETHNOPHARMACOLOGY 297(2022):15. |
入库方式： OAI收割
来源：上海药物研究所
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