PMID- 29425589 OWN - NLM STAT- MEDLINE DCOM- 20180726 LR - 20180726 IS - 1875-5364 (Electronic) IS - 1875-5364 (Linking) VI - 16 IP - 1 DP - 2018 Jan TI - Puerarin attenuates angiotensin II-induced cardiac fibroblast proliferation via the promotion of catalase activity and the inhibition of hydrogen peroxide-dependent Rac-1 activation. PG - 41-52 LID - S1875-5364(18)30028-1 [pii] LID - 10.1016/S1875-5364(18)30028-1 [doi] AB - The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H(2)O(2) in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac1 was dependent on the levels of intracellular H(2)O(2). Puerarin blocked the phosphorylation of extracellular regulated protein kinases (ERK)1/2, abolished activator protein (AP)-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of H(2)O(2)-dependent Rac1 activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregulation of catalase expression and H(2)O(2)-dependent Rac1 activation. CI - Copyright (c) 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved. FAU - Chen, Gang AU - Chen G AD - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. FAU - Pan, Shi-Fen AU - Pan SF AD - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. FAU - Cui, Xiang-Li AU - Cui XL AD - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. FAU - Liu, Li-Hong AU - Liu LH AD - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. Electronic address: hongllh@126.com. LA - eng PT - Journal Article PL - China TA - Chin J Nat Med JT - Chinese journal of natural medicines JID - 101504416 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Isoflavones) RN - 0 (Neuropeptides) RN - 0 (Rac1 protein, mouse) RN - 0 (Transcription Factor AP-1) RN - 11128-99-7 (Angiotensin II) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.6 (Catalase) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) RN - Z9W8997416 (puerarin) SB - IM MH - Angiotensin II/pharmacology MH - Angiotensin II Type 1 Receptor Blockers/pharmacology MH - Animals MH - Animals, Newborn MH - Catalase/genetics/*metabolism MH - Cell Proliferation/*drug effects MH - Cells, Cultured MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism MH - Fibroblasts MH - Gene Expression Regulation/drug effects MH - Heart/*drug effects MH - Hydrogen Peroxide/*metabolism/pharmacology MH - Isoflavones/*pharmacology MH - Mice MH - Myocardium/cytology/enzymology/metabolism MH - NADPH Oxidases/antagonists & inhibitors/metabolism MH - Neuropeptides/*metabolism MH - Signal Transduction/drug effects MH - Transcription Factor AP-1/antagonists & inhibitors/metabolism MH - Transcriptional Activation/drug effects MH - rac1 GTP-Binding Protein/*metabolism OTO - NOTNLM OT - Angiontensin II OT - Catalase OT - Hydrogen peroxide OT - Puerarin EDAT- 2018/02/10 06:00 MHDA- 2018/07/27 06:00 CRDT- 2018/02/10 06:00 PHST- 2017/05/11 00:00 [received] PHST- 2018/02/10 06:00 [entrez] PHST- 2018/02/10 06:00 [pubmed] PHST- 2018/07/27 06:00 [medline] AID - S1875-5364(18)30028-1 [pii] AID - 10.1016/S1875-5364(18)30028-1 [doi] PST - ppublish SO - Chin J Nat Med. 2018 Jan;16(1):41-52. doi: 10.1016/S1875-5364(18)30028-1.