Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product
(+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate (HOEC) was isolated from Incarvillea mairei var. granditlora (Wehrhahn) Grierson. The plants of the Incarvillea genus have long been used as folk medicines for the treatment of inflammation-related diseases in China. 5-Lipoxygenase (5-LOX), a key enz...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-09-01
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| Series: | European Journal of Inflammation |
| Online Access: | https://doi.org/10.1177/1721727X1201000306 |
| _version_ | 1828462074173325312 |
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| author | L. Li H-W. Zeng F. Liu J-G. Zhang R-C. Yue W-Q. Lu X. Yuan W-X. Dai H. Yuan Q-Y. Sun J. Huang H-L. Li Y-S. Li L. Shan W-D. Zhang |
| author_facet | L. Li H-W. Zeng F. Liu J-G. Zhang R-C. Yue W-Q. Lu X. Yuan W-X. Dai H. Yuan Q-Y. Sun J. Huang H-L. Li Y-S. Li L. Shan W-D. Zhang |
| author_sort | L. Li |
| collection | DOAJ |
| description | (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate (HOEC) was isolated from Incarvillea mairei var. granditlora (Wehrhahn) Grierson. The plants of the Incarvillea genus have long been used as folk medicines for the treatment of inflammation-related diseases in China. 5-Lipoxygenase (5-LOX), a key enzyme in the arachidonic acid (AA) cascade, was identified as a potential target of HOEC by a pulldown assay, and then extensively validated by biosensor-based affinity detection, enzyme-based activity assays, cell-based AA metabolite analysis and computer-aided AA network simulation. Further in vivo studies of AA-induced ear oedema, ovalbumin (OVA)-induced lung inflammation and collagen-induced arthritis demonstrated the anti-inflammatory potency and validated the therapeutic target of HOEC. This work revealed that HOEC acted as an anti-inflammatory agent targeting 5-LOX, which not only confirmed the key role of 5-LOX in inflammation but also provided a paradigm for the exploration of natural product mechanisms of action. |
| first_indexed | 2024-12-11T02:29:40Z |
| format | Article |
| id | doaj.art-bdc3a38f21fc45d287d10ad7f5d6ae1e |
| institution | Directory Open Access Journal |
| issn | 1721-727X |
| language | English |
| last_indexed | 2024-12-11T02:29:40Z |
| publishDate | 2012-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | European Journal of Inflammation |
| spelling | doaj.art-bdc3a38f21fc45d287d10ad7f5d6ae1e2022-12-22T01:23:51ZengSAGE PublishingEuropean Journal of Inflammation1721-727X2012-09-011010.1177/1721727X1201000306Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural ProductL. Li0H-W. Zeng1F. Liu2J-G. Zhang3R-C. Yue4W-Q. Lu5X. Yuan6W-X. Dai7H. Yuan8Q-Y. Sun9J. Huang10H-L. Li11Y-S. Li12L. Shan13W-D. Zhang14 Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiaotong University, Shanghai, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China School of Pharmacy, East China University of Science and Technology, Shanghai, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiaotong University, Shanghai, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China School of Pharmacy, East China University of Science and Technology, Shanghai, PR China School of Pharmacy, East China University of Science and Technology, Shanghai, PR China Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China Department of Natural Product Chemistry, Second Military Medical University, Shanghai, PR China Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiaotong University, Shanghai, PR China(+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate (HOEC) was isolated from Incarvillea mairei var. granditlora (Wehrhahn) Grierson. The plants of the Incarvillea genus have long been used as folk medicines for the treatment of inflammation-related diseases in China. 5-Lipoxygenase (5-LOX), a key enzyme in the arachidonic acid (AA) cascade, was identified as a potential target of HOEC by a pulldown assay, and then extensively validated by biosensor-based affinity detection, enzyme-based activity assays, cell-based AA metabolite analysis and computer-aided AA network simulation. Further in vivo studies of AA-induced ear oedema, ovalbumin (OVA)-induced lung inflammation and collagen-induced arthritis demonstrated the anti-inflammatory potency and validated the therapeutic target of HOEC. This work revealed that HOEC acted as an anti-inflammatory agent targeting 5-LOX, which not only confirmed the key role of 5-LOX in inflammation but also provided a paradigm for the exploration of natural product mechanisms of action.https://doi.org/10.1177/1721727X1201000306 |
| spellingShingle | L. Li H-W. Zeng F. Liu J-G. Zhang R-C. Yue W-Q. Lu X. Yuan W-X. Dai H. Yuan Q-Y. Sun J. Huang H-L. Li Y-S. Li L. Shan W-D. Zhang Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product European Journal of Inflammation |
| title | Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product |
| title_full | Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product |
| title_fullStr | Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product |
| title_full_unstemmed | Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product |
| title_short | Target Identification and Validation of (+)-2-(1-Hydroxyl-4-Oxocyclohexyl) Ethyl Caffeate, an Anti-Inflammatory Natural Product |
| title_sort | target identification and validation of 2 1 hydroxyl 4 oxocyclohexyl ethyl caffeate an anti inflammatory natural product |
| url | https://doi.org/10.1177/1721727X1201000306 |
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