{"created":"2021-03-01T06:39:43.412519+00:00","id":31309,"links":{},"metadata":{"_buckets":{"deposit":"32cccc72-8bc7-4a36-9b0a-7f041040a26f"},"_deposit":{"id":"31309","owners":[],"pid":{"revision_id":0,"type":"depid","value":"31309"},"status":"published"},"_oai":{"id":"oai:nagoya.repo.nii.ac.jp:00031309","sets":["1903:1904:1905"]},"author_link":["103279","103280","103281","103282","103283","103284"],"item_10_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-11-15","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"173436","bibliographicVolumeNumber":"887","bibliographic_titles":[{"bibliographic_title":"European Journal of Pharmacology","bibliographic_titleLang":"en"}]}]},"item_10_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The tight junction (TJ) is the apical-most intercellular junction complex, serving as a biological barrier of intercellular spaces between epithelial cells. The TJ's integrity is maintained by a key protein–protein interaction between C-terminal motifs of claudins (CLDs) and the postsynaptic density 95 (PSD-95)/discs large/zonula occludens 1 (ZO-1; PDZ) domains of ZO-1. Weak but direct interaction of baicalin and its aglycon, baicalein—which are pharmacologically active components of Chinese skullcap (Radix scutellariae)—with ZO-1(PDZ1) have been observed in NMR experiments. Next, we observed TJ-mitigating activity of these flavonoids against Madin-Darby canine kidney (MDCK) II cells with the downregulation of subcellular localization of CLD-2 at TJs. Meanwhile, baicalein—but not baicalin—induced a slender morphological change of MDCK cells' shape from their normal cobblestone-like shapes. Since baicalin and baicalein did not induce a localization change of occludin (OCLN), a “partial” epithelial–mesenchymal transition (EMT) induced by these flavonoids was considered. SB431542, an ALK-5 inhibitor, reversed the CLD-2 downregulation of both baicalin and baicalein, while SB431542 did not reverse the slender morphology. In contrast, the MEK/ERK inhibitor U0126 reversed the slender shape change. Thus, in addition to inhibition of the ZO-1–CLD interaction, activation of both transforming growth factor-β (TGF-β) and MEK/ERK signaling pathways have been suggested to be involved in TJ reduction by these flavonoids. Finally, we demonstrated that baicalin enhanced the permeability of fluorescence-labeled insulin via the paracellular pathway of the Caco-2 cell layer. We propose that baicalin, baicalein, and Radix scutellariae extract are useful as drug absorption enhancers.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"ファイル公開：2021-11-15","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_10_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier","subitem_publisher_language":"en"}]},"item_10_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.ejphar.2020.173436","subitem_relation_type_select":"DOI"}}]},"item_10_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/"}]},"item_10_select_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"author"}]},"item_10_source_id_61":{"attribute_name":"ISSN（print）","attribute_value_mlt":[{"subitem_source_identifier":"0014-2999","subitem_source_identifier_type":"PISSN"}]},"item_1615787544753":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Hisada, Misaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"103279","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hiranuma, Minami","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"103280","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nakashima, Mio","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"103281","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Goda, Natsuko","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"103282","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tenno, Takeshi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"103283","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hiroaki, Hidekazu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"103284","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-11-15"}],"displaytype":"detail","filename":"EJP-53411R3-accepted-NUrepository.pdf","filesize":[{"value":"1.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"EJP-53411R3-accepted-NUrepository","objectType":"fulltext","url":"https://nagoya.repo.nii.ac.jp/record/31309/files/EJP-53411R3-accepted-NUrepository.pdf"},"version_id":"6deda2fc-f51c-4dfa-8f36-556d2f1298dd"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"PDZ domain Inhibitor","subitem_subject_scheme":"Other"},{"subitem_subject":"Tight junction","subitem_subject_scheme":"Other"},{"subitem_subject":"Zonula occludens-1","subitem_subject_scheme":"Other"},{"subitem_subject":"NMR","subitem_subject_scheme":"Other"},{"subitem_subject":"Baicalin","subitem_subject_scheme":"Other"},{"subitem_subject":"Absorption enhancer","subitem_subject_scheme":"Other"},{"subitem_subject":"TGF-β signaling pathway","subitem_subject_scheme":"Other"},{"subitem_subject":"Epithelial cell barrier","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)","subitem_title_language":"en"}]},"item_type_id":"10","owner":"1","path":["1905"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-02-08"},"publish_date":"2021-02-08","publish_status":"0","recid":"31309","relation_version_is_last":true,"title":["High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-01-16T04:24:19.162667+00:00"}