Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking
文献类型：期刊论文
| 作者 | Gao, Lei1,3; Kong, Xinqin1,3; Wu, Wenyong1,2; Feng, Zijin1; Zhi, Haijuan1; Zhang, Zijia1; Long, Huali1; Lei, Min1 ; Hou, Jinjun1; Wu, Wanying1,3
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| 刊名 | FRONTIERS IN PHARMACOLOGY
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| 出版日期 | 2022-05-30 |
| 卷号 | 13页码:12 |
| 关键词 | Uncaria anti-hypertensive arachidonic acid metabolites sEH = soluble epoxide hydrolase EETS metabolomics molecular docking indole alkaloids |
| DOI | 10.3389/fphar.2022.909631 |
| 通讯作者 | Hou, Jinjun(jinjun_hou@simm.ac.cn) ; Wu, Wanying(wanyingwu@simm.ac.cn) |
| 英文摘要 | Uncaria rhynchophylla (Miq). Miq. (UR), as a traditional Chinese medicine, was employed in treating hypertension as a safe and effective therapy. The pharmacological properties of UR have characteristics of multiple biological targets and multiple functional pathways. Hypertension is related to impaired metabolic homeostasis and is especially associated with the abnormal regulation of arachidonic acid metabolites, the classical cardiovascular active compounds. This study aimed to examine the anti-hypertensive effect of UR extract (URE) and its regulating role in differential metabolic pathways. The results showed that daily administration of URE at a dose of 4 g crude drug/kg orally could exert hypotensive effects on spontaneously hypertensive rats (SHRs) for 8 weeks. Non-targeted metabolomics analysis of the plasma samples suggested that the anti-hypertension effect of URE in SHRs was associated with the reorganization of the perturbed metabolic network, such as the pathways of glycerophospholipid metabolism, linoleic acid metabolism, and arachidonic acid metabolism. For the targeted metabolomics, twenty-eight arachidonic acid metabolites in SHRs were quantitatively analyzed for the first time based on ultra-high performance liquid chromatography-tandem mass spectrometry method after URE administration. URE restored the functions of these cardiovascular active compounds and rebalanced the dynamics of arachidonic acid metabolic flux. Among them, the inhibition of soluble epoxide hydrolase (sEH) enzyme activity and up-regulation of vasodilators epoxyeicosatrienoic acids (EETs) were identified as contributors to the anti-hypertension effect of URE on SHRs, and sEH represented an attractive and promising drug-binding target of URE. With the molecular docking approach, 13 potential anti-hypertension ingredients as well as sEH inhibitors were discovered, which were worthy of further investigation and verification in future studies. |
| WOS关键词 | SOLUBLE EPOXIDE HYDROLASE ; BLOOD-PRESSURE ; CYTOCHROME-P450 ; HEALTH ; OMICS |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000810978300001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/301425]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hou, Jinjun; Wu, Wanying |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Engn Lab TCM Standardizat Technol, Shanghai, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Lei,Kong, Xinqin,Wu, Wenyong,et al. Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking[J]. FRONTIERS IN PHARMACOLOGY,2022,13:12. |
| APA | Gao, Lei.,Kong, Xinqin.,Wu, Wenyong.,Feng, Zijin.,Zhi, Haijuan.,...&Guo, De-an.(2022).Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking.FRONTIERS IN PHARMACOLOGY,13,12. |
| MLA | Gao, Lei,et al."Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking".FRONTIERS IN PHARMACOLOGY 13(2022):12. |
入库方式： OAI收割
来源：上海药物研究所
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