PMID- 37277556 OWN - NLM STAT- MEDLINE DCOM- 20230922 LR - 20230922 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 48 IP - 11 DP - 2023 Nov TI - Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway. PG - 3363-3377 LID - 10.1007/s11064-023-03961-5 [doi] AB - More and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-alpha) in LPS-treated BV-2 cells. (1)H-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Gao, Li AU - Gao L AD - Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road Xiaodain District, Taiyuan, 030006, Shanxi, China. gaoli87@sxu.edu.cn. AD - Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, 030006, Shanxi, China. gaoli87@sxu.edu.cn. FAU - Liu, Yu-Xin AU - Liu YX AD - Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road Xiaodain District, Taiyuan, 030006, Shanxi, China. AD - Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, 030006, Shanxi, China. FAU - Zhou, Yu-Zhi AU - Zhou YZ AD - Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road Xiaodain District, Taiyuan, 030006, Shanxi, China. AD - Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, 030006, Shanxi, China. FAU - Qin, Xue-Mei AU - Qin XM AD - Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road Xiaodain District, Taiyuan, 030006, Shanxi, China. qinxm@sxu.edu.cn. AD - Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, 030006, Shanxi, China. qinxm@sxu.edu.cn. LA - eng GR - 202203021211292/Fundamental Research Program of Shanxi Province,China/ GR - 81603319/National Natural Science Foundation of China, China/ PT - Journal Article DEP - 20230605 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 49QAH60606 (baicalein) RN - 0 (Lipopolysaccharides) RN - 0 (Flavanones) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (NF-kappa B) RN - 0 (STAT3 protein, human) RN - 0 (STAT3 Transcription Factor) SB - IM MH - Humans MH - *Lipopolysaccharides/toxicity MH - Neuroinflammatory Diseases MH - *Flavanones/pharmacology/therapeutic use MH - Inflammation/drug therapy/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Microglia/metabolism MH - NF-kappa B/metabolism MH - STAT3 Transcription Factor/metabolism OTO - NOTNLM OT - Baicalein OT - Glycolysis OT - Microglia OT - STAT3 EDAT- 2023/06/06 01:11 MHDA- 2023/09/22 06:42 CRDT- 2023/06/05 23:23 PHST- 2022/12/27 00:00 [received] PHST- 2023/05/23 00:00 [accepted] PHST- 2023/05/08 00:00 [revised] PHST- 2023/09/22 06:42 [medline] PHST- 2023/06/06 01:11 [pubmed] PHST- 2023/06/05 23:23 [entrez] AID - 10.1007/s11064-023-03961-5 [pii] AID - 10.1007/s11064-023-03961-5 [doi] PST - ppublish SO - Neurochem Res. 2023 Nov;48(11):3363-3377. doi: 10.1007/s11064-023-03961-5. Epub 2023 Jun 5.