PMID- 37046194 OWN - NLM STAT- Publisher LR - 20230412 IS - 1875-5402 (Electronic) IS - 1386-2073 (Linking) DP - 2023 Apr 12 TI - Linarin Ameliorates Diabetic Liver Injury by Alleviating Oxidative Stress and Inflammation through the Inhibition of AKR1B1. LID - 10.2174/1386207326666230412084201 [doi] AB - AIMS: The study aims to find a new functional additive for diabetic liver injury. BACKGROUND: It is well-established that type 2 diabetes mellitus (T2DM) is a metabolic disease with multiple complications and places a significant health and economic burden on modern society. Linarin is a natural flavonoid isolated from Asteraceae and Lamiaceae, which has beneficial effects in preventing and treating metabolic diseases such as nonalcoholic steatohepatitis and diabetes. OBJECTIVE: We aimed to investigate the pharmacological effect and underlying mechanism of linarin on T2DM-associated liver injury in vivo and in vitro. METHODS: Using a high-glucose and high-palmitic acid-induced hepatocyte injury model and a type 2 diabetic rat model. Following linarin treatment, serum biochemical parameters, liver histology, and lipid profiles of rats were examined. Oxidative stress index and inflammatory response were detected in vivo and in vitro. The expression level of AKR1B1 in rat liver tissues and in vitro cells was detected by western blot and by real-time fluorescent quantitative PCR. RESULTS: The present study found that linarin could prevent oxidative stress and inflammation. In high-fat-fed diabetic rats, linarin administration (15, 30, and 60 mg/kg/day) reduced hepatic lipid accumulation, oxidative stress, and inflammation. Linarin (20 muM) significantly alleviated oxidative stress, inflammation, and apoptosis induced by high glucose combined with palmitic acid in LX-2 cells. Western blotting and overexpression experiments showed that these effects were related to AKR1B1 inhibition in vivo and in vitro. CONCLUSION: This study indicated that linarin could protect against liver injury in T2DM by alleviating oxidative stress and inflammation mediated by AKR1B1 and may be a promising additive for diabetic liver injury therapy. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Wang, Tong AU - Wang T AD - Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. FAU - Shan, Meng-Ya AU - Shan MY AD - Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. FAU - Tang, Cui-Yao AU - Tang CY AD - Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. FAU - Cheng, Mao-Yuan AU - Cheng MY AD - Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. FAU - Chen, Bin AU - Chen B AD - Department of Biochemistry and Molecular Biology, Army Medical University, Chongqing 400038, China. FAU - Yan, Jun AU - Yan J AD - Department 1, Research Institute of Surgery & Daping Hospital, Army Medical Center of Chinese People's Liberation Army, Army Medical University, Chongqing 400042, China. FAU - Xu, Zi-Hui AU - Xu ZH AD - Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China. LA - eng PT - Journal Article DEP - 20230412 PL - United Arab Emirates TA - Comb Chem High Throughput Screen JT - Combinatorial chemistry & high throughput screening JID - 9810948 SB - IM OTO - NOTNLM OT - AKR1B1. OT - Diabetic liver injury OT - Inflammation OT - Linarin OT - Oxidative stress OT - Type 2 diabetes mellitus EDAT- 2023/04/13 06:00 MHDA- 2023/04/13 06:00 CRDT- 2023/04/12 23:43 PHST- 2022/07/18 00:00 [received] PHST- 2023/02/08 00:00 [revised] PHST- 2023/02/23 00:00 [accepted] PHST- 2023/04/12 23:43 [entrez] PHST- 2023/04/13 06:00 [pubmed] PHST- 2023/04/13 06:00 [medline] AID - CCHTS-EPUB-130872 [pii] AID - 10.2174/1386207326666230412084201 [doi] PST - aheadofprint SO - Comb Chem High Throughput Screen. 2023 Apr 12. doi: 10.2174/1386207326666230412084201.