{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:25:44Z","timestamp":1780496744578,"version":"3.54.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Picroside II (PII), an iridoid glycoside extracted from the rhizomes and stems of the genus Picroside, exhibits pronounced hepatoprotective properties. Pre-administration of PII protects against acute liver injury caused by D-galactosamine (D-Gal), carbon tetrachloride (CCl4), and acetaminophen (APAP). This study aimed to elucidate the ramifications of PII administration subsequent to the initiation of acute hepatic injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Exploring the role of PII treatment in APAP-treated cell and rat models and in D-Gal and CCl4-treated rat models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In rats, APAP treatment increased serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels and decreased glutathione activity and the fluidity of the liver mitochondrial membrane. In L-02 cells, APAP exposure resulted in a decrement in membrane potential, an augmentation in the liberation of reactive oxygen species, and an acceleration of apoptotic processes. Moreover, PII pre-administration protected against D-Gal-induced acute hepatic injury and CCl4-induced chronic hepatic injury in rodent models, whereas PII administration post-injury aggravated CCl4-induced chronic hepatic injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results suggest that the effects of PII depend on the hepatic physiological or pathological state at the time of intervention. While PII possesses the potential to avert drug-induced acute hepatic injury through the mitigation of oxidative stress, its administration post-injury may exacerbate the hepatic damage, underscoring the critical importance of timing in therapeutic interventions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/toxres\/tfae073","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T14:38:17Z","timestamp":1715956697000},"source":"Crossref","is-referenced-by-count":2,"title":["The paradox of Picroside II: As a natural antioxidant, but may instead futher aggravate liver injury by exacerbating mitochondrial oxidative stress"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3969-0443","authenticated-orcid":false,"given":"Xu","family":"Yifan","sequence":"first","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center , State Key Laboratory of Natural Medicines, , 24 Tongjiaxiang, Gulou 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