PMID- 35370712 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220405 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Efficacy and Mechanism of Buyang Huanwu Decoction in Patients With Ischemic Heart Failure: A Randomized, Double-Blind, Placebo-Controlled Trial Combined With Proteomic Analysis. PG - 831208 LID - 10.3389/fphar.2022.831208 [doi] LID - 831208 AB - Objective: Buyang Huanwu Decoction (BYHW), a famous herbal prescription in traditional Chinese medicine (TCM), has been used for 200 years for treating ischemic heart failure (IHF). This study aims to assess the efficacy and safety of BYHW combined with guideline-guided pharmacotherapy in patients with IHF and explore the biological mechanism by which BYHW exerts its efficacy. Methods: In the multicenter, double-blind, randomized controlled trial, a total of 80 patients with IHF were randomized to receive BYHW or placebo for 3 months. The primary efficacy endpoints were New York Heart Association (NYHA) classification, TCM syndrome scores, N-terminal pro-B-type natriuretic peptide (NT-ProBNP), whereas the mechanism exploration endpoints included energy metabolism parameters and coagulation function parameters. In addition, we performed the proteomic study of the serum of patients after treatment by label-free quantification technology to verify the candidate target proteins and pathways. Results: After 3 months of treatment, the NYHA classification, TCM syndrome scores, and the percentage of subjects with at least 30% reduction in NT-ProBNP were significantly improved in the BYHW group, compared with the control group (p < 0.05); BYHW treatment also significantly regulated blood glucose, blood lipid levels, ameliorated energy metabolism and improved coagulation function parameters. There were no significant differences in safety endpoints between the two groups. In addition, we obtained 56 differentially expressed proteins by proteomics, including 20 upregulated proteins and 36 downregulated proteins. Bioinformatic analysis revealed the mechanism of BYHW treatment was significantly related to complement and coagulation cascades, cholesterol metabolism, NF-kappa B signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways. Among these differentially regulated proteins, fibrinogen gamma (FGG), fibrinogen beta (FGB), Carboxypeptidase B2 (CPB2), Coagulation factor XIII A (F13A1), Intercellular adhesion molecule1 (ICAM1), Apolipoprotein C-II(APOC2), Apolipoprotein C-I(APOC1), and CD44 were found to be signature proteins associated with the efficacy of BYHW against IHF. Conclusion: BYHW treatment can further improve cardiac dysfunction and clinical symptoms in IHF based on standard therapy without apparent adverse effects. Additionally, BYHW may play a therapeutic role in IHF by improving energy metabolism and regulating coagulation function through multiple targets and pathways. CI - Copyright (c) 2022 Zhu, Wei, Li, Wang, Ren, Li, Ma, Wang, Qiao, Zhou and Liu. FAU - Zhu, Mingjun AU - Zhu M AD - First Affiliated Hospital of Henan University of CM, Zhengzhou, China. FAU - Wei, Jingjing AU - Wei J AD - Henan University of Chinese Medicine, Zhengzhou, China. FAU - Li, Ying AU - Li Y AD - Beijing Key Laboratory of Pharmacology of Chinese Materia Region, Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, National Clinical Research Center of Cardiovascular Disease of Traditional Chinese Medicine, Beijing, China. FAU - Wang, Yongxia AU - Wang Y AD - First Affiliated Hospital of Henan University of CM, Zhengzhou, China. FAU - Ren, Junguo AU - Ren J AD - Beijing Key Laboratory of Pharmacology of Chinese Materia Region, Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, National Clinical Research Center of Cardiovascular Disease of Traditional Chinese Medicine, Beijing, China. FAU - Li, Bin AU - Li B AD - First Affiliated Hospital of Henan University of CM, Zhengzhou, China. FAU - Ma, Bo AU - Ma B AD - Beijing Key Laboratory of Pharmacology of Chinese Materia Region, Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, National Clinical Research Center of Cardiovascular Disease of Traditional Chinese Medicine, Beijing, China. FAU - Wang, Xinlu AU - Wang X AD - First Affiliated Hospital of Henan University of CM, Zhengzhou, China. FAU - Qiao, Lijie AU - Qiao L AD - Henan University of Chinese Medicine, Zhengzhou, China. FAU - Zhou, Cheng AU - Zhou C AD - Henan University of Chinese Medicine, Zhengzhou, China. FAU - Liu, Jianxun AU - Liu J AD - Beijing Key Laboratory of Pharmacology of Chinese Materia Region, Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, National Clinical Research Center of Cardiovascular Disease of Traditional Chinese Medicine, Beijing, China. LA - eng PT - Journal Article DEP - 20220318 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8971676 OTO - NOTNLM OT - Buyang Huanwu decoction OT - coagulation function OT - energy metabolism OT - ischemic heart failure OT - proteomics OT - randomized controlled trial 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. The reviewer MW declared a shared parent affiliation with the author(s) YL, JR, BM, and JL to the handling editor at the time of review. EDAT- 2022/04/05 06:00 MHDA- 2022/04/05 06:01 PMCR- 2022/03/18 CRDT- 2022/04/04 05:28 PHST- 2021/12/08 00:00 [received] PHST- 2022/03/04 00:00 [accepted] PHST- 2022/04/04 05:28 [entrez] PHST- 2022/04/05 06:00 [pubmed] PHST- 2022/04/05 06:01 [medline] PHST- 2022/03/18 00:00 [pmc-release] AID - 831208 [pii] AID - 10.3389/fphar.2022.831208 [doi] PST - epublish SO - Front Pharmacol. 2022 Mar 18;13:831208. doi: 10.3389/fphar.2022.831208. eCollection 2022.