{"id":11613,"date":"2023-07-03T08:41:10","date_gmt":"2023-07-03T08:41:10","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=11613"},"modified":"2023-07-03T08:41:10","modified_gmt":"2023-07-03T08:41:10","slug":"2023-assay-for-evaluation-of-proarrhythmic-effects-of-herbal-products-case-study-with-12-evodia-preparations","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2023-assay-for-evaluation-of-proarrhythmic-effects-of-herbal-products-case-study-with-12-evodia-preparations\/","title":{"rendered":"2023 &#8211; Assay for evaluation of proarrhythmic effects of herbal products: Case study with 12 Evodia preparations"},"content":{"rendered":"<p>Guidelines for preclinical\u00a0drug development\u00a0reduce the occurrence of arrhythmia-related side effects. Besides ample evidence for the presence of arrhythmogenic substances in plants, there is no consensus on a research strategy for the evaluation of proarrhythmic effects of herbal products. Here, we propose a cardiac safety assay for the detection of proarrhythmic effects of plant extracts based on the experimental approaches described in the Comprehensive\u00a0<em>In vitro<\/em>\u00a0Proarrhythmia\u00a0Assay (CiPA). Microelectrode array studies (MEAs) and voltage sensing optical technique on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were combined with ionic current measurements in mammalian cell lines<em>, In-silico<\/em>\u00a0simulations of cardiac action potentials (APs) and statistic regression analysis. Proarrhythmic effects of 12\u00a0<em>Evodia<\/em>\u00a0preparations, containing different amounts of the hERG inhibitors\u00a0dehydroevodiamine\u00a0(DHE) and hortiamine were analysed. Extracts produced different\u00a0prolongation\u00a0of the AP, occurrence of early after depolarisations and triangulation of the AP in hiPSC-CMs depending on the contents of the hERG inhibitors. DHE and hortiamine dose-dependently prolonged the field potential duration in hiPSC-CMs studied with MEAs.\u00a0<em>In-silico<\/em>\u00a0simulations of ventricular AP support a scenario where proarrhythmic effects of\u00a0<em>Evodia<\/em>\u00a0extracts are predominantly caused by the content of the selective hERG inhibitors. Statistic regression analysis revealed a high torsadogenic risk for both compounds that was comparable to drugs assigned to the high-risk category in a CiPA study.<\/p>\n<p>Read more in the publication <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2214750023000471\">here<\/a>.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42,44],"resource_type":[75],"application_areas":[53,77],"therapeutic_areas":[54,143],"target_categories":[61],"target_families":[333],"targets":[],"resource_keyword":[],"class_list":["post-11613","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","products_tags-patchliner","resource_type-publication","application_areas-assay-development-and-validation","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-kv-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/11613","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=11613"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=11613"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=11613"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=11613"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=11613"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=11613"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=11613"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=11613"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=11613"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}