title: Total Flavonoids from Rosa laevigata Michx Fruit Ameliorates Hepatic Ischemia/Reperfusion Injury through Inhibition of Oxidative Stress and Inflammation in Rats.
abstract: The effects of total flavonoids (TFs) from Rosa laevigata Michx fruit against liver damage and cerebral ischemia/reperfusion (I/R) injury have been reported, but its action on hepatic I/R injury remains unknown. In this work, the effects and possible mechanisms of TFs against hepatic I/R injury were examined using a 70% partial hepatic warm ischemia rat model. The results demonstrated TFs decreased serum aspartate transaminase (AST), alanine aminotransferase (ALT), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) activities, improved liver histopathology and ultrastructure through hematoxylin-eosin (HE) staining and electron microscope observation. In addition, TFs significantly decreased malondialdehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which indicated that TFs alleviated oxidative stress caused by I/R injury. RT-PCR results proved that TFs downregulated the gene levels of inflammatory factors including interleukin-1 beta (IL-1β), interleukin-1 (IL-6), and tumor necrosis factor alpha (TNF-α). Further research indicated that TF-induced hepatoprotection was completed through inhibiting TLR4/MyD88 and activating Sirt1/Nrf2 signaling pathways. Blockade of the TLR4 pathway by TFs inhibited NF-κB and AP-1 transcriptional activities and inflammatory reaction. Activation of Sirt1/Nrf2 pathway by TFs increased the protein levels of HO-1 and GST to improve oxidative stress. Collectively, these findingsconfirmed the potent effects of TFs against hepatic I/R injury, which should be developed as a candidate for the prevention of this disease.
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. taoxufengdalian@163.com.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Occupational and Environmental of Health, Dalian Medical University, No. 9 Western Section of Lushun South Road, Dalian 116044, China. qimengdy2020@163.com.
authors.forename: Xiance
authors.initials: X
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Linaxu_632@126.com.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Lianhongyin_1980@163.com.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Xuhan2002zs@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Yanqi_1976@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Youweixu_1964@163.com.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Yanyanzhao_2009@126.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. yuhao.1988517zs@163.com.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. jinyongpeng2008@126.com.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D006505:Hepatitis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D027826:Rosa / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D005419:Flavonoids; D018836:Inflammation Mediators; D010936:Plant Extracts
keywords: Rosa laevigata Michx fruit; hepatic ischemia/reperfusion; inflammation; oxidative stress; total flavonoids