Abstract
Hypertension is a lifestyle-related disease which often leads to serious conditions such as heart disease and cerebral hemorrhage. Angiotensin II (Ang II) plays an important role in regulating cardiovascular homeostasis. Consequently, antagonists that block the interaction of Ang II with its receptors are thought to be effective in the suppression of hypertension. In this study, we searched for plant compounds that had antagonist-like activity toward Ang II receptors. From among 435 plant samples, we found that EtOH extract from the resin of sweet gum Liquidambar styraciflua strongly inhibited Ang II signaling. We isolated benzyl benzoate and benzyl cinnamate from this extract and found that those compounds inhibited the function of Ang II in a dose-dependent manner without cytotoxicity. An in vivo study showed that benzyl benzoate significantly suppressed Ang II-induced hypertension in mice. In addition, we synthesized more than 40 derivatives of benzyl benzoate and found that the meta-methyl and 3-methylbenzyl 2'-nitrobenzoate derivatives showed about 10-fold higher activity than benzyl benzoate itself. Thus, benzyl benzoate, its derivatives, and benzyl cinnamate may be useful for reducing hypertension.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II / antagonists & inhibitors
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Angiotensin II / metabolism
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Angiotensin II Type 1 Receptor Blockers / isolation & purification
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Angiotensin II Type 1 Receptor Blockers / pharmacology*
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Angiotensin II Type 1 Receptor Blockers / therapeutic use
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Animals
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Antihypertensive Agents / chemistry
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Antihypertensive Agents / isolation & purification*
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Antihypertensive Agents / pharmacology
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Benzoates / chemistry
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Benzoates / isolation & purification
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Benzoates / pharmacology*
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Benzyl Compounds / chemistry
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Benzyl Compounds / isolation & purification
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Benzyl Compounds / pharmacology
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Blood Pressure / drug effects
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CHO Cells
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Calcium / analysis
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Calcium / metabolism
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Cell Survival / drug effects
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Cinnamates / chemistry
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Cinnamates / isolation & purification
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Cinnamates / pharmacology
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Cricetinae
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Cricetulus
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HeLa Cells
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Humans
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Hypertension / drug therapy*
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Liquidambar / chemistry*
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Magnetic Resonance Spectroscopy
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Male
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Mice
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Receptor, Angiotensin, Type 1 / metabolism*
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Spectrometry, Mass, Electrospray Ionization
Substances
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Angiotensin II Type 1 Receptor Blockers
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Antihypertensive Agents
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Benzoates
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Benzyl Compounds
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Cinnamates
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Receptor, Angiotensin, Type 1
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Angiotensin II
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benzyl benzoate
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Calcium
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benzyl cinnamate