PMID- 34069176 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210615 IS - 2075-1729 (Print) IS - 2075-1729 (Electronic) IS - 2075-1729 (Linking) VI - 11 IP - 5 DP - 2021 May 14 TI - Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress. LID - 10.3390/life11050445 [doi] LID - 445 AB - NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H(2)O(2) was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 muM) and in vitro (K3O, 20 muM). Additionally, K3O (40 muM) reduced neutrophil aggregation in vivo. K3O (20 muM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H(2)O(2)-exposed HepG2 cells. In the mechanism study, keap1, nrf2, tnf-alpha, and il-6 mRNA were all significantly reversed by K3O (20 muM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H(2)O(2)-exposed HepG2 cells after they were treated with K3O (20 muM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model. FAU - Deng, Yang AU - Deng Y AUID- ORCID: 0000-0001-9233-9500 AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Ma, Ji AU - Ma J AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Weng, Xin AU - Weng X AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Wang, Yuqin AU - Wang Y AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Li, Maoru AU - Li M AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Yang, Tingting AU - Yang T AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Dou, Zhiyang AU - Dou Z AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Yin, Zhiqi AU - Yin Z AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. FAU - Shang, Jing AU - Shang J AD - School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. AD - Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University. Nanjing 211198, China. AD - State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. LA - eng GR - 2019ZX09301-156/the National Science Technology Major Project of China/ PT - Journal Article DEP - 20210514 PL - Switzerland TA - Life (Basel) JT - Life (Basel, Switzerland) JID - 101580444 PMC - PMC8155963 OTO - NOTNLM OT - high-cholesterol diet. OT - inflammation OT - kaempferol-3-O-glucuronide OT - non-alcoholic fatty liver disease OT - oxidative stress COIS- The authors declare no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/06/03 06:01 PMCR- 2021/05/14 CRDT- 2021/06/02 01:24 PHST- 2021/04/08 00:00 [received] PHST- 2021/05/07 00:00 [revised] PHST- 2021/05/10 00:00 [accepted] PHST- 2021/06/02 01:24 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/06/03 06:01 [medline] PHST- 2021/05/14 00:00 [pmc-release] AID - life11050445 [pii] AID - life-11-00445 [pii] AID - 10.3390/life11050445 [doi] PST - epublish SO - Life (Basel). 2021 May 14;11(5):445. doi: 10.3390/life11050445.