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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2025-06-01
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| author | Yanwen Sun Chunyu Fan Liyi Chen Xueting Cui Kouharu Otsuki Mi Zhang Feng Qiu Liqin Ding Wei Li |
| author_facet | Yanwen Sun Chunyu Fan Liyi Chen Xueting Cui Kouharu Otsuki Mi Zhang Feng Qiu Liqin Ding Wei Li |
| author_sort | Yanwen Sun |
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| description | <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. |
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| institution | Kabale University |
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| spelling | doaj-art-e2cabd492274415a94aa22126f6092572025-08-20T03:27:41ZengMDPI AGPlants2223-77472025-06-011412174210.3390/plants14121742Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory ActivityYanwen Sun0Chunyu Fan1Liyi Chen2Xueting Cui3Kouharu Otsuki4Mi Zhang5Feng Qiu6Liqin Ding7Wei Li8Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaTianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaTianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaTianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaFaculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanFaculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, JapanTianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaFaculty of Pharmaceutical Sciences, Toho University, Funabashi 274-8510, Japan<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.https://www.mdpi.com/2223-7747/14/12/1742<i>Cimicifuga heracleifolia</i>indole alkaloidsphenolic amidessoluble epoxide hydrolase |
| spellingShingle | Yanwen Sun Chunyu Fan Liyi Chen Xueting Cui Kouharu Otsuki Mi Zhang Feng Qiu Liqin Ding Wei Li Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity Plants <i>Cimicifuga heracleifolia</i> indole alkaloids phenolic amides soluble epoxide hydrolase |
| title | Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity |
| title_full | Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity |
| title_fullStr | Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity |
| title_full_unstemmed | Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity |
| title_short | Indole Alkaloids and Phenolic Amides from the Rhizomes of <i>Cimicifuga heracleifolia</i> and Their In Vitro Soluble Epoxide Hydrolase (sEH) Inhibitory Activity |
| title_sort | indole alkaloids and phenolic amides from the rhizomes of i cimicifuga heracleifolia i and their in vitro soluble epoxide hydrolase seh inhibitory activity |
| topic | <i>Cimicifuga heracleifolia</i> indole alkaloids phenolic amides soluble epoxide hydrolase |
| url | https://www.mdpi.com/2223-7747/14/12/1742 |
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