{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:56:32Z","timestamp":1760147792398,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University","award":["RSP2023R301"],"award-info":[{"award-number":["RSP2023R301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p &lt; 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate\u2013cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p &lt; 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.<\/jats:p>","DOI":"10.3390\/molecules28052257","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T01:36:09Z","timestamp":1677634569000},"page":"2257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates"],"prefix":"10.3390","volume":"28","author":[{"given":"Riffat","family":"Batool","sequence":"first","affiliation":[{"name":"Directorate of BASR, Allama Iqbal Open University, Islamabad 44310, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Rashid","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Umar","family":"Ijaz","sequence":"additional","affiliation":[{"name":"Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irum","family":"Naz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Biochemistry, Biotechnology and Bioinformatics, Faculty of Chemical and Biological Sciences, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afsheen","family":"Batool","sequence":"additional","affiliation":[{"name":"Faculty RMU & Allied Hospitals, Rawalpindi Medical University and Allied Hospital, Rawalpindi 46000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zartash","family":"Zahra","sequence":"additional","affiliation":[{"name":"Gujrat Institute of Management Sciences, Peer Mehar Ali Shah Arid Agriculture University, Gujrat 50700, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safia","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Botany, Sardar Bahadur Khan Women\u2019s University Quetta, Quetta 87300, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad N.","family":"Uddin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-0378","authenticated-orcid":false,"given":"Mohsin","family":"Kazi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-7141","authenticated-orcid":false,"given":"Raees","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s10753-019-00973-8","article-title":"Umbelliferone ameliorates ccl4-induced liver fibrosis in rats by upregulating ppar\u03b3 and attenuating oxidative stress, inflammation, and tgf-\u03b21\/smad3 signaling","volume":"42","author":"Mahmoud","year":"2019","journal-title":"Inflammation"},{"key":"ref_2","first-page":"447","article-title":"Curcumin protects against liver fibrosis by attenuating infiltration of gr1hi monocytes through inhibition of monocyte chemoattractant protein-1","volume":"21","author":"Huang","year":"2016","journal-title":"Discov. 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