論文 - 詳細
| RRC ID | 1407 |
|---|---|
| 著者 | Matsui S, Matsumoto H, Sonoda Y, Ando K, Aizu-Yokota E, Sato T, Kasahara T. |
| タイトル | Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. |
| ジャーナル | Int Immunopharmacol |
| Abstract |
Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an anti-allergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNF-alpha and IL-4. Moreover, we examined the structure-activity relationships of GL to explore more beneficial compounds. 18alpha,beta-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18alpha,beta-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18alpha,beta-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18alpha,beta-GL but was weaker. Both 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-11-deoxo-olean-12-en-30-oic acid (11-deoxo-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3beta-[(2-O-beta-D-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18alpha,beta-GL. 3beta-[(2-O-beta-d-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations lower than 18alpha,beta-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity. |
| 巻・号 | 4(13) |
| ページ | 1633-44 |
| 公開日 | 2004-12-15 |
| DOI | 10.1016/j.intimp.2004.07.023 |
| PII | S1567-5769(04)00249-8 |
| PMID | 15454116 |
| PMC | PMC7106177 |
| MeSH | Animals Cell Line* Cell Survival / drug effects Chemokine CCL11 Chemokines, CC / antagonists & inhibitors* Chemokines, CC / metabolism Down-Regulation / drug effects Down-Regulation / genetics* Down-Regulation / immunology Enzyme-Linked Immunosorbent Assay / methods Fetus Fibroblasts / metabolism Fibroblasts / pathology Glycyrrhetinic Acid / analogs & derivatives* Glycyrrhetinic Acid / immunology* Glycyrrhetinic Acid / pharmacology Glycyrrhizic Acid / immunology* Glycyrrhizic Acid / pharmacology Humans Inhibitory Concentration 50 Interleukin-8 / antagonists & inhibitors* Interleukin-8 / metabolism Lung / metabolism Lung / pathology Molecular Structure Neutrophils / physiology Oligosaccharides / classification Oligosaccharides / immunology Oligosaccharides / pharmacology Polymerase Chain Reaction / methods RNA, Messenger / genetics RNA, Messenger / metabolism Structure-Activity Relationship |
| IF | 3.943 |
| 引用数 | 114 |
| WOS 分野 | PHARMACOLOGY & PHARMACY IMMUNOLOGY |
| 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 | |
| ヒト・動物細胞 | HFL-I(RCB0521) |