論文 - 詳細
| RRC ID | 75209 |
|---|---|
| 著者 | Oikawa D, Yamashita S, Takahashi S, Waki T, Kikuchi K, Abe T, Katayama T, Nakayama T. |
| タイトル | (+)-Sesamin, a sesame lignan, is a potent inhibitor of gut bacterial tryptophan indole-lyase that is a key enzyme in chronic kidney disease pathogenesis. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
The progression of chronic kidney disease (CKD) increases the risks of cardiovascular morbidity and end-stage kidney disease. Indoxyl sulfate (IS), which is derived from dietary l-tryptophan by the action of bacterial l-tryptophan indole-lyase (TIL) in the gut, serves as a uremic toxin that exacerbates CKD-related kidney disorder. A mouse model previously showed that inhibition of TIL by 2-aza-l-tyrosine effectively reduced the plasma IS level, causing the recovery of renal damage. In this study, we found that (+)-sesamin and related lignans, which occur abundantly in sesame seeds, inhibit intestinal bacteria TILs. Kinetic studies revealed that (+)-sesamin and sesamol competitively inhibited Escherichia coli TIL (EcTIL) with Ki values of 7 μM and 14 μM, respectively. These Ki values were smaller than that of 2-aza-l-tyrosine (143 μM). Molecular docking simulation of (+)-sesamin- (or sesamol-)binding to EcTIL predicted that these inhibitors potentially bind near the active site of EcTIL, where the cofactor pyridoxal 5'-phosphate is bound, consistent with the kinetic results. (+)-Sesamin is a phytochemical with a long history of consumption and is generally regarded as safe. Hence, dietary supplementation of (+)-sesamin encapsulated in enteric capsules could be a promising mechanism-based strategy to prevent CKD progression. Moreover, the present findings would provide a new structural basis for designing more potent TIL inhibitors for the development of mechanism-based therapeutic drugs to treat CKD. |
| 巻・号 | 590 |
| ページ | 158-162 |
| 公開日 | 2022-1-29 |
| DOI | 10.1016/j.bbrc.2021.12.088 |
| PII | S0006-291X(21)01731-9 |
| PMID | 34974305 |
| MeSH | Benzodioxoles / chemistry Benzodioxoles / pharmacology Dioxoles / chemistry Dioxoles / pharmacology* Enzyme Inhibitors / pharmacology* Gastrointestinal Microbiome* / drug effects Kinetics Lignans / chemistry Lignans / pharmacology* Molecular Docking Simulation Phenols / chemistry Phenols / pharmacology Renal Insufficiency, Chronic / enzymology* Renal Insufficiency, Chronic / etiology* Sesamum / chemistry* Tryptophanase / antagonists & inhibitors* Tryptophanase / metabolism |
| 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 | 1 |
| 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 | |
| 一般微生物 | JCM 5827 JCM 1658 JCM 1238 JCM 1672 JCM 1673 |