Blockade of the dioxin pathway by herbal medicine Formula bupleuri minor:: Identification of active entities for suppression of AhR activation
Blockade of the dioxin pathway by herbal medicine Formula bupleuri minor:: Identification of active entities for suppression of AhR activation
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DOI：
10.1248/bpb.31.838
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发表时间：
2008-05-01
影响因子：
2
通讯作者：
Kitamura, Masanori
中科院分区：
文献类型：
--
作者：
Kasai, Ayumi;Hiramatsu, Nobuhiko;Kitamura, Masanori
包括二恶英在内的环境污染物激活芳烃受体（AhR）并引起广泛的病理学。AhR拮抗剂的开发将有助于预防和治疗与AhR激活相关的疾病。为了实现这一目标，我们的目的是寻找潜在的AhR拮抗剂中草药使用二恶英响应元件为基础的传感通过分泌型碱性磷酸酶（DRESSA）。通过初步的粗筛选，从20种中药中选出4种配方进行第二次细筛选。我们发现，只有小丁内酯（TJ-9）显著抑制2，3，7，8-四氯二苯并-p-二恶英对AhR的激活。在TJ-9的7种原料药提取物中，黄连和甘草对TJ-9的二恶英拮抗作用最强。柴胡、柴胡等部分成分对AhR有较强的激活作用。在黄芪和丹参的12种主要成分中，鉴定出黄芪中的甘草香豆素、甘草酸和染料木素以及丹参中的黄芩素、汉黄芩素和大豆苷元对AhR有明显的拮抗作用。其中，黄芩素最有效地阻断由香烟烟雾触发的AhR激活，这是AhR的强激活剂。本文鉴定的拮抗物质可用于预防与AhR异常激活相关的疾病。
Environmental pollutants including dioxins activate the aryl hydrocarbon receptor (AhR) and cause a wide range of pathologies. Development of AhR antagonists will be useful for prevention and treatment of the diseases related to AhR activation. Towards this goal, we aimed at seeking for potential AhR antagonists in herbal medicines using the dioxin responsive element-based sensing via secreted alkaline phosphatase (DRESSA). Through initial rough screening, 4 formulae were selected from 20 herbal medicines and subjected to the second, detailed screening. We found that only Formula bupleuri minor (TJ-9) significantly inhibited activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Among 7 raw herb extracts in TJ-9, Glycyrrllizae Radix and Scutellariae Radix were responsible for the antagonistic effect of TJ-9 against dioxin. Some constituents including Bupleuri Radix and Zingiberis Rhizoma rather activated AhR. Among 12 major constituents of Glycyrrhizae Radix and Scutellariae Radix, we identified that licopyranocoumarin, glycyrrhizic acid and genistein in Glycyrrhizae Radix and baicalein, wogonin and daidzein in Scutellariae Radix had substantial antagonistic effects on AhR. Among these, baicalein most effectively blocked activation of AhR triggered by cigarette smoke, a strong activator of AhR. The antagonistic substances identified here may be useful for prevention from diseases associated with aberrant activation of AhR.