Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity

<i>Cimicifuga heracleifolia</i> is a perennial herb that belongs to the Ranunculaceae family. Its dried rhizomes are a source of Cimicifugae Rhizoma, a traditional Chinese medicine used for detoxification, the treatment of febrile diseases, and the prevention of pathogenic invasion. In t...

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Main Authors: Yanwen Sun, Chunyu Fan, Liyi Chen, Xueting Cui, Kouharu Otsuki, Mi Zhang, Feng Qiu, Liqin Ding, Wei Li
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Plants
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Online Access:https://www.mdpi.com/2223-7747/14/12/1742
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Summary:<i>Cimicifuga heracleifolia</i> is a perennial herb that belongs to the Ranunculaceae family. Its dried rhizomes are a source of Cimicifugae Rhizoma, a traditional Chinese medicine used for detoxification, the treatment of febrile diseases, and the prevention of pathogenic invasion. In the present study, a phytochemical investigation of the rhizomes of <i>C. heracleifolia</i> resulted in the isolation of three indole alkaloids (<b>1</b>–<b>3</b>) and seven phenolic amides (<b>4</b>–<b>10</b>), including three new compounds, 6-methoxy-3-(3-methyl-1-oxo-2-butenyl) 1<i>H</i> indole (<b>1</b>), (3<i>R</i>)-1-(<i>β</i>-<span style="font-variant: small-caps;">d</span>-glucopyranosyl)-3-hydroxy-3-(3-methylbutyl)-2-oxindole (<b>3</b>), and <i>N</i>-acetyldopamine-3-<i>O</i>-<i>β</i>-<span style="font-variant: small-caps;">d</span>-allopyranoside (<b>4</b>). Their structures were elucidated using extensive physicochemical and spectroscopic analyses. All the isolated compounds were evaluated for their inhibitory activity against soluble epoxide hydrolase (sEH). The results showed that cimicifugamide A (<b>6</b>) exhibited the most potent inhibitory activity, with an IC₅₀ value of 8.74 μM, followed by cimicifugamide (<b>7</b>), demethoxycimicifugamide (<b>8</b>), and <i>N</i>-<i>trans</i>-feruloyl tyramine (<b>10</b>), with IC<sub>50</sub> values ranging from 15.63 to 20.58 μM. Kinetic analysis revealed that compound <b>6</b> inhibited sEH through a non-competitive mechanism.
ISSN:2223-7747