論文 - 詳細
| RRC ID | 56626 |
|---|---|
| 著者 | Choodej S, Pudhom K, Mitsunaga T. |
| タイトル | Inhibition of TNF-α-Induced Inflammation by Sesquiterpene Lactones from Saussurea lappa and Semi-Synthetic Analogues. |
| ジャーナル | Planta Med |
| Abstract |
We investigated the tumor necrosis factor-alpha (TNF-α) inhibitory activity of sesquiterpenes from Saussurea lappa root extracts. According to the hexane and EtOAc extracts showing significant activity with IC50 values of 0.5 and 1.0 µg/mL, respectively, chromatographic fractionation of the extracts was performed and led to the isolation of 10 sesquiterpenes (1: -10: ). Costunolide (1: ), a major compound, and dehydrocostus lactone (4: ) exhibited high efficiency in decreasing TNF-α levels, with IC50 values of 2.05 and 2.06 µM, respectively. In addition, sesquiterpene analogues were synthesized to establish their structure-activity relationship (SAR) profile. Among the semi-synthetic analogues, compounds 6A: and 16: showed the most potent activity with IC50 values of 1.84 and 1.97 µM, respectively. More importantly, compound 6A: showed less toxicity than costunolide and 16: . These results provided the first SAR profile of sesquiterpene lactones and indicated that the α-methylene-γ-lactone moiety plays a crucial role in TNF-α inhibition. Additionally, the epoxide derivative 6A: might represent a lead compound for further anti-TNF-α therapies, owing to its potent activity and reduced toxicity. |
| 巻・号 | 84(5) |
| ページ | 329-335 |
| 公開日 | 2018-3-1 |
| DOI | 10.1055/s-0043-120115 |
| PMID | 28962049 |
| MeSH | Anti-Inflammatory Agents / chemistry Anti-Inflammatory Agents / pharmacology* Inflammation / drug therapy* Inhibitory Concentration 50 Lactones / chemistry Lactones / isolation & purification Lactones / pharmacology* Molecular Structure Plant Extracts / chemistry Plant Extracts / isolation & purification Plant Extracts / pharmacology* Plant Roots / chemistry Saussurea / chemistry* Sesquiterpenes / chemistry Sesquiterpenes / isolation & purification Sesquiterpenes / pharmacology* Structure-Activity Relationship Tumor Necrosis Factor-alpha / adverse effects |
| IF | 2.746 |
| 引用数 | 11 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |