PMID- 36903503 OWN - NLM STAT- MEDLINE DCOM- 20230316 LR - 20230316 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 28 IP - 5 DP - 2023 Feb 28 TI - Linum corymbulosum Protects Rats against CCl(4)-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates. LID - 10.3390/molecules28052257 [doi] LID - 2257 AB - 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 (CCl(4))-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. CCl(4) administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H(2)O(2), 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 CCl(4) 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-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl(4)-administered rats. Similarly, the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl(4) administration to rats. Co-administration of LCM along with CCl(4) to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl(4)-treated rats. However, LCM administration to CCl(4)-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. FAU - Batool, Riffat AU - Batool R AD - Directorate of BASR, Allama Iqbal Open University, Islamabad 44310, Pakistan. FAU - Khan, Muhammad Rashid AU - Khan MR AD - Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. FAU - Ijaz, Muhammad Umar AU - Ijaz MU AD - Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan. FAU - Naz, Irum AU - Naz I AD - Department of Biochemistry, Institute of Biochemistry, Biotechnology and Bioinformatics, Faculty of Chemical and Biological Sciences, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan. FAU - Batool, Afsheen AU - Batool A AD - Faculty RMU & Allied Hospitals, Rawalpindi Medical University and Allied Hospital, Rawalpindi 46000, Pakistan. FAU - Ali, Saima AU - Ali S AD - Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. FAU - Zahra, Zartash AU - Zahra Z AD - Gujrat Institute of Management Sciences, Peer Mehar Ali Shah Arid Agriculture University, Gujrat 50700, Pakistan. FAU - Gul, Safia AU - Gul S AD - Department of Botany, Sardar Bahadur Khan Women's University Quetta, Quetta 87300, Pakistan. FAU - Uddin, Mohammad N AU - Uddin MN AD - College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA. FAU - Kazi, Mohsin AU - Kazi M AUID- ORCID: 0000-0002-5611-0378 AD - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. FAU - Khan, Raees AU - Khan R AUID- ORCID: 0000-0003-1388-7141 AD - Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. LA - eng PT - Journal Article DEP - 20230228 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Antioxidants) RN - CL2T97X0V0 (Carbon Tetrachloride) RN - BBX060AN9V (Hydrogen Peroxide) RN - 0 (Plant Extracts) SB - IM MH - Animals MH - Rats MH - Antioxidants/chemistry MH - Carbon Tetrachloride/toxicity MH - *Chemical and Drug Induced Liver Injury/metabolism MH - *Flax/metabolism MH - Hydrogen Peroxide/metabolism MH - Liver MH - *Liver Diseases/metabolism MH - Oxidative Stress MH - Plant Extracts/chemistry MH - Rats, Sprague-Dawley MH - *Unfolded Protein Response PMC - PMC10004795 OTO - NOTNLM OT - ER stress OT - Linum corymbulosum OT - antioxidant OT - hepatic markers OT - pro-inflammatory intermediates COIS- The Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/12 06:00 MHDA- 2023/03/15 06:00 PMCR- 2023/02/28 CRDT- 2023/03/11 01:26 PHST- 2023/01/06 00:00 [received] PHST- 2023/02/08 00:00 [revised] PHST- 2023/02/15 00:00 [accepted] PHST- 2023/03/11 01:26 [entrez] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/02/28 00:00 [pmc-release] AID - molecules28052257 [pii] AID - molecules-28-02257 [pii] AID - 10.3390/molecules28052257 [doi] PST - epublish SO - Molecules. 2023 Feb 28;28(5):2257. doi: 10.3390/molecules28052257.