{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:39:07Z","timestamp":1789623547584,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002949","name":"Government of Jiangsu Province","doi-asserted-by":"publisher","award":["MS2022087"],"award-info":[{"award-number":["MS2022087"]}],"id":[{"id":"10.13039\/501100002949","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute pancreatitis represents an inflammatory disease featuring pancreatic necrosis and inflammation. Inflammatory injury of pancreatic acinar cells (PACs) is critically involved in the initiation and progression of acute pancreatitis. Pyroptosis, a new kind of programmed cell death concomitant with a low\u2010grade inflammatory reaction, plays a function in acute pancreatitis pathology. It is unclear whether saikosaponin d (SSd), a pharmacologically active natural product, could protect PACs by regulating pyroptosis. Here, we established a PAC injury model in vitro using cerulein to treat AR42J cells. SSd restored viability and proliferation and lowered the release of pancreatic enzymes and inflammatory interleukins in cerulein\u2010treated AR42J cells. Cerulein\u2010induced pyroptosis was evidenced by typical ultrastructural changes and NLRP3\/caspase\u20101 activation in AR42J cells, but SSd attenuated cerulein\u2010induced pyroptosis and inhibited NLRP3\/caspase\u20101 pathway. Mechanically, SSd reduced mitochondrial damage and mtDNA release, and blocked cGAS\u2010STING signaling in AR42J cells treated with cerulein, contributing to the inhibition of NLRP3\u2010mediated pyroptosis. Furthermore, SSd abolished cerulein\u2010elevated oxidative stress in AR42J cells, leading to the mitigation of mitochondrial damage and inhibition of cGAS\u2010STING signaling and pyroptosis. In conclusion, SSd protected PACs against cerulein\u2010induced pyroptosis by alleviating mitochondrial damage and inhibiting the cGAS\u2010STING pathway, and it could be a therapeutic candidate for acute pancreatitis.<\/jats:p>","DOI":"10.1002\/jat.4594","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T03:25:39Z","timestamp":1710127539000},"page":"1005-1013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Saikosaponin d protects pancreatic acinar cells against cerulein\u2010induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS\u2010STING pathway"],"prefix":"10.1002","volume":"44","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Emergency Kunshan Hospital of Traditional Chinese Medicine  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xirong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach Kunshan Hospital of Traditional Chinese Medicine  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency Kunshan Hospital of Traditional Chinese Medicine  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Emergency Kunshan Hospital of Traditional Chinese Medicine  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach Kunshan Hospital of Traditional Chinese Medicine  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6914-042X","authenticated-orcid":false,"given":"Dan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Emergency Kunshan Hospital of Traditional Chinese Medicine  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.02.038"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-022-01729-w"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110795"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2023.05.003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2004.tb00330.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/2058738420950593"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12305"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2022.04.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2019.01.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01855012"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02511-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15499"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0244-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154766"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08476"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112239"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-073119-095439"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101215"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0336-5"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202210988"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5489553"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102305"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.06.009"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jox12040027"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.23736\/S2724-5985.20.02699-9"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0000000000001017"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101781"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165685"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01046-w"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00507-5"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.07.007"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113862073262404231004053116"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2023.12194"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13186"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T12:34:43Z","timestamp":1760531683000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,11]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/jat.4594"],"URL":"https:\/\/doi.org\/10.1002\/jat.4594","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,11]]},"assertion":[{"value":"2023-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}