PMID- 35847050 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220719 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Baicalein Prevents Fructose-Induced Hepatic Steatosis in Rats: In the Regulation of Fatty Acid De Novo Synthesis, Fatty Acid Elongation and Fatty Acid Oxidation. PG - 917329 LID - 10.3389/fphar.2022.917329 [doi] LID - 917329 AB - Non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic fibrosis and even hepatocellular carcinoma, is a liver disease worldwide without approved therapeutic drugs. Baicalein (BAL), a flavonoid compound extracted from the Traditional Chinese Medicine (TCM) Scutellariae Radix (Scutellaria baicalensis Georgi.), has been used in TCM clinical practice for thousands of years to treat liver diseases due to its "hepatoprotective effect". However, the underlying liver-protecting mechanisms remain largely unknown. Here, we found that oral administration of BAL significantly decreased excess serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) as well as hepatic TG in fructose-fed rats. Attenuation of the increased vacuolization and Oil Red O staining area was evident on hepatic histological examination in BAL-treated rats. Mechanistically, results of RNA-sequencing, western-blot, real-time quantitative PCR (RT-qPCR) and hepatic metabolomics analyses indicated that BAL decreased fructose-induced excessive nuclear expressions of mature sterol regulatory element-binding protein 1c (mSREBP1c) and carbohydrate response element-binding protein (ChREBP), which led to the decline of lipogenic molecules [including fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), elongation of very long chain fatty acids 6 (ELOVL6), acetyl-CoA carboxylase (ACC)], accompanying with the alternation of hepatic fatty acids composition. Meanwhile, BAL enhanced fatty acid oxidation by activating AMPK/PGC1alpha signaling axis and PPARalpha signal pathway, which elicited high expression of carnitine palmitoyl transferase 1alpha (CPT1alpha) and Acyl-CoA oxidase 1 (ACO1) in livers of fructose-fed rats, respectively. BAL ameliorated fructose-induced hepatic steatosis, which is associated with regulating fatty acid synthesis, elongation and oxidation. CI - Copyright (c) 2022 Li, Zhang, Wang, Chen, Chen, Ke, Zuo and Wang. FAU - Li, Pan AU - Li P AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. FAU - Zhang, Ruoyu AU - Zhang R AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. FAU - Wang, Meng AU - Wang M AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. FAU - Chen, Yuwei AU - Chen Y AD - The Pharmacy Department, the Second People's Hospital of Jiulongpo District, Chongqing, China. FAU - Chen, Zhiwei AU - Chen Z AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. FAU - Ke, Xiumei AU - Ke X AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. FAU - Zuo, Ling AU - Zuo L AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. FAU - Wang, Jianwei AU - Wang J AD - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20220630 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9280198 OTO - NOTNLM OT - Baicalein OT - fatty acid elongation OT - fatty acid oxidation OT - fatty acid synthesis OT - hepatic steatosis OT - non-alcoholic fatty liver COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/19 06:00 MHDA- 2022/07/19 06:01 PMCR- 2022/06/30 CRDT- 2022/07/18 04:10 PHST- 2022/04/11 00:00 [received] PHST- 2022/06/13 00:00 [accepted] PHST- 2022/07/18 04:10 [entrez] PHST- 2022/07/19 06:00 [pubmed] PHST- 2022/07/19 06:01 [medline] PHST- 2022/06/30 00:00 [pmc-release] AID - 917329 [pii] AID - 10.3389/fphar.2022.917329 [doi] PST - epublish SO - Front Pharmacol. 2022 Jun 30;13:917329. doi: 10.3389/fphar.2022.917329. eCollection 2022.