{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:45:05Z","timestamp":1778874305349,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bio-Synergy Research Project","award":["NRF-2013M3A9C4078156"],"award-info":[{"award-number":["NRF-2013M3A9C4078156"]}]},{"name":"Bio-Synergy Research Project","award":["21153MFDS605"],"award-info":[{"award-number":["21153MFDS605"]}]},{"name":"Ministry of Science","award":["NRF-2013M3A9C4078156"],"award-info":[{"award-number":["NRF-2013M3A9C4078156"]}]},{"name":"Ministry of Science","award":["21153MFDS605"],"award-info":[{"award-number":["21153MFDS605"]}]},{"name":"Korean Ministry of Food and Drug Safety","award":["NRF-2013M3A9C4078156"],"award-info":[{"award-number":["NRF-2013M3A9C4078156"]}]},{"name":"Korean Ministry of Food and Drug Safety","award":["21153MFDS605"],"award-info":[{"award-number":["21153MFDS605"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Emodin, an emerging mycotoxin, is known to be hepatotoxic, but its mechanism remains unclear. We hypothesized that emodin could induce endoplasmic reticulum (ER) stress through the inositol-requiring enzyme 1 alpha (IRE1\u03b1)\u2013X-box-binding protein 1 (XBP1) pathway and apoptosis, which are closely correlated and contribute to hepatotoxicity. To test this hypothesis, a novel IRE1\u03b1 inhibitor, STF-083010, was used. An MTT assay was used to evaluate metabolic activity, and quantitative PCR and western blotting were used to investigate the gene and protein expression of ER stress or apoptosis-related markers. Apoptosis was evaluated with flow cytometry. Results showed that emodin induced cytotoxicity in a dose-dependent manner in HepG2 cells and upregulated the expression of binding immunoglobulin protein (BiP), C\/EBP homologous protein (CHOP), IRE1\u03b1, spliced XBP1, the B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)\/Bcl-2 ratio, and cleaved caspase-3. Cotreatment with emodin and STF-083010 led to the downregulation of BiP and upregulation of CHOP, the Bax\/Bcl-2 ratio, and cleaved caspase-3 compared with single treatment with emodin. Furthermore, the apoptosis rate was increased in a dose-dependent manner with emodin treatment. Thus, emodin induced ER stress in HepG2 cells by activating the IRE1\u03b1\u2013XBP1 axis and induced apoptosis, indicating that emodin can cause hepatotoxicity.<\/jats:p>","DOI":"10.3390\/toxins15070455","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:58:11Z","timestamp":1689213491000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Emodin, an Emerging Mycotoxin, Induces Endoplasmic Reticulum Stress-Related Hepatotoxicity through IRE1\u03b1\u2013XBP1 Axis in HepG2 Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Su Been","family":"Park","sequence":"first","affiliation":[{"name":"School of Food Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gun Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Eun","family":"Park","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyang Sook","family":"Chun","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gaj\u0119cki, M.T., Gaj\u0119cka, M., and Zielonka, \u0141. 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