{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:52:56Z","timestamp":1791175976708,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate the effects of Spica Prunellae (SP) on CCl\n                      <jats:sub>4<\/jats:sub>\n                      -induced acute liver injury (ALI) in mice and its regulation of the endoplasmic reticulum stress pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the toxicity test, ICR mice were administered SP decoction (2\u00a0g\/kg, crude herb\/mouse weight) by gavage for 10 days. Liver and kidney tissues were collected for H&amp;amp;E staining, and serum levels of liver function (AST, ALT) and renal (BUN, SCR) function indicators were measured. After confirming safety, 48 ICR mice were randomly assigned to normal, model, high-, medium-, and low-dose SP, and positive control groups (\n                      <jats:italic>n<\/jats:italic>\n                      = 8 per group). All mice, except the normal group, received a 10% CCl\n                      <jats:sub>4<\/jats:sub>\n                      \/peanut oil intraperitoneal injection to induce ALI. The normal and model groups received saline; the positive control group received bifendate; and the SP groups received corresponding SP doses by daily gavage for 10 days. Body weight, liver, spleen, and thymus indices were recorded; ELISA measured serum ALT and AST, and liver MDA and SOD; liver histopathology was assessed by H&amp;amp;E staining; hepatocyte ultrastructure was examined\n                      <jats:italic>via<\/jats:italic>\n                      transmission electron microscopy; and ER stress-related proteins (GRP78, IRE1\u03b1, and JNK) expressions were determined by Western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SP caused minimal damage to hepatic and renal tissues in mice at 2\u00a0g\/kg, with no significant changes in liver (ALT, AST) or renal (BUN, SCR) function indicators (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;gt; 0.05). In the ALI model vs. model group, SP-treated groups demonstrated improved organ indices (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), reduced serum ALT and AST levels (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), increased SOD levels (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), and significantly decreased MDA levels (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). Histopathological analysis revealed clear attenuation of liver tissue damage, with mild nuclear deformation. Endoplasmic reticulum degranulation was alleviated, showing an organized arrangement and preserved cellular structure. Compared to the model group, GRP78 and IRE1\u03b1 expression were significantly declined in the positive control and SP-treated groups (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), and JNK expression was downregulated (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest the involvement of the GRP78\/IRE1\u03b1\/JNK signaling pathway in the hepatoprotective action of SP against CCl\n                      <jats:sub>4<\/jats:sub>\n                      -induced ALI.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1909409","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:34:03Z","timestamp":1791174843000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spica Prunellae attenuates ER stress via GRP78\/IRE1\u03b1\/JNK pathway in CCL4-induced acute liver injury in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanjie","family":"Wang","sequence":"first","affiliation":[{"name":"School of Food and Biological Engineering, Hezhou University\/Guangxi Key Laboratory of Healthcare Food Science and Technology","place":["Hezhou, China"]},{"name":"School of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaping","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Hezhou University\/Guangxi Key Laboratory of Healthcare Food Science and Technology","place":["Hezhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaomei","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Han","sequence":"additional","affiliation":[{"name":"School of Materials and Chemistry, Hezhou University","place":["Hezhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Materials and Chemistry, Hezhou University","place":["Hezhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12935-023-02931-9","article-title":"Cell surface GRP78: a potential mechanism of therapeutic resistant tumors","volume":"23","author":"Amaresan","year":"2023","journal-title":"Cancer Cell Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1126\/science.aal1962","article-title":"Mouse models of acute and chronic hepacivirus infection","volume":"357","author":"Billerbeck","year":"2017","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.cgh.2018.08.016","article-title":"A multicenter study into causes of severe acute liver injury","volume":"17","author":"Breu","year":"2019","journal-title":"Clin. 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