{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:28:22Z","timestamp":1778218102616,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatic ischaemia\u2013reperfusion (IR) injury is a serious clinical issue, especially in patients with type 2 diabetes mellitus (T2DM). As mitochondria play a critical role in the regulation of IR\u2010induced liver damage, mitochondria\u2010targeted treatment is of the utmost significance for improving outcomes. The present study explored the mitoprotective role of combined ginsenoside\u2010MC1 (GMC1) and irisin administration in diabetic rats with hepatic IR injury. T2DM was induced in male Sprague\u2013Dawley rats with a high\u2010fat diet and a low\u2010dose streptozotocin. Following the induction of diabetes, hepatic IR injury was induced. Rats were pretreated with GMC1 and\/or irisin for 28\u00a0days prior to IR injury. Liver function was evaluated by quantitation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Histopathological changes were observed with haematoxylin\u2013eosin staining. Apoptotic markers (Bax, Bcl\u20102, cleaved caspase\u20103) and signalling proteins (AMP\u2010activated protein kinase (AMPK), c\u2010Jun N\u2010terminal kinase (JNK)) were examined by western blotting. Mitochondrial function was evaluated by measuring reactive oxygen species, membrane potential and ATP content. Oxidative stress markers, such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx), were also measured. Combined therapy lowered AST, ALT and LDH levels, and histopathological injury (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.05). It restored mitochondrial function; upregulated Bcl\u20102 and phosphorylated AMPK expression; downregulated Bax, cleaved caspase\u20103 and phosphorylated JNK expression; and reduced MDA levels, while elevating SOD and GPx activity (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.05). AMPK inhibition by compound C reversed these protective effects. GMC1\u2013irisin combination therapy safeguarded diabetic rats against IR\u2010caused liver damage through suppressing mitochondrial apoptosis by AMPK\/JNK signalling, a hopeful therapeutic approach in diabetic patients.\n                  <\/jats:p>","DOI":"10.1113\/ep092982","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T17:44:28Z","timestamp":1757526268000},"page":"751-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of combined ginsenoside\u2010MC1 and irisin on mitochondrial apoptosis in diabetic rats with hepatic reperfusion injury: Role of AMPK\/JNK signalling"],"prefix":"10.1113","volume":"111","author":[{"given":"Jie","family":"Lin","sequence":"first","affiliation":[{"name":"Organ Transplantation Center The First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center The First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Ma","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center The First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-9948","authenticated-orcid":false,"given":"Bo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center The First Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0504-0822","authenticated-orcid":false,"given":"Yabin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University  Huaian Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.01.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-009-1112-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.10.019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1184774"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30875"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.03.004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112563"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2006.02.021"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103258"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2022.05.020"},{"issue":"3","key":"e_1_2_9_12_1","first-page":"129","article-title":"L\u2010limonene reduces aortic artery atherosclerosis by inhibiting oxidative stress\/inflammatory responses in diabetic rats fed high\u2010fat diet","volume":"66","author":"Han X.","year":"2023","journal-title":"Journal of Physiological Investigation"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S500719"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2019.08.006"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101131"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00534-009-0155-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-008-0681-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.12.020"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36365-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.935263"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.757336"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6346(99)00055-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.18295\/squmj.2016.16.02.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1590\/s0102-865020180080000008"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.1.161"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110323"},{"issue":"6","key":"e_1_2_9_28_1","first-page":"1183","article-title":"Monotherapy versus combination therapy","volume":"90","author":"Patel S. 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