Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Autor: Bai Y; Northwest University, Xi'an 710069, China., Jia P; Northwest University, Xi'an 710069, China., Zhao Y; Northwest University, Xi'an 710069, China., Yang L; Northwest University, Xi'an 710069, China., Wang X; Northwest University, Xi'an 710069, China., Wang X; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China., Wang J; Northwest University, Xi'an 710069, China., Zhong N; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China., Deng H; School of Biotechnology, Jiangnan University, Wuxi 214122, China., Du L; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China., Fang J; Northwest University, Xi'an 710069, China., Xue Y; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China., Chen Y; Northwest University, Xi'an 710069, China., Gao S; Northwest University, Xi'an 710069, China., Feng Y; Northwest University, Xi'an 710069, China., Yan Y; School of Biotechnology, Jiangnan University, Wuxi 214122, China., Xiong T; School of Biotechnology, Jiangnan University, Wuxi 214122, China., Liu J; School of Biotechnology, Jiangnan University, Wuxi 214122, China., Sun Y; Northwest University, Xi'an 710069, China., Xie J; Northwest University, Xi'an 710069, China., He X; Northwest University, Xi'an 710069, China., An X; Northwest University, Xi'an 710069, China., Liu P; Northwest University, Xi'an 710069, China., Xu J; School of Biotechnology, Jiangnan University, Wuxi 214122, China., Qin F; Northwest University, Xi'an 710069, China., Meng X; Northwest University, Xi'an 710069, China., Yin Q; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China; Institute of Vascular Medicine, Peking University, Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China., Yang Q; Northwest University, Xi'an 710069, China; Institute of Vascular Medicine, Peking University, Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China., Gao R; Northwest University, Xi'an 710069, China., Gao X; Northwest University, Xi'an 710069, China., Luo K; Northwest University, Xi'an 710069, China., Li Q; Northwest University, Xi'an 710069, China., Wang X; Northwest University, Xi'an 710069, China., Liang J; Northwest University, Xi'an 710069, China., Yang P; Department of Infectious Diseases, Xi'an North Hospital, Xi'an 710043, China., Zhang Y; Northwest University, Xi'an 710069, China., Liao S; Northwest University, Xi'an 710069, China; Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK., Wang S; Northwest University, Xi'an 710069, China., Zhao X; Northwest University, Xi'an 710069, China., Xiao C; Northwest University, Xi'an 710069, China., Yu J; Northwest University, Xi'an 710069, China., Liu Q; Shaanxi Provincial People's Hospital, Xi'an 710068, China., Wang R; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China., Peng N; Shaanxi Provincial People's Hospital, Xi'an 710068, China., Wang X; Shaanxi Provincial People's Hospital, Xi'an 710068, China., Guo J; Shaanxi Institute for Food and Drug Control, Xi'an 710065, China., Li X; Shaanxi Institute for Food and Drug Control, Xi'an 710065, China., Liu H; Shaanxi Institute for Food and Drug Control, Xi'an 710065, China., Bai Y; Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK; School of Information and Control Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China., Li Z; Institute of Vascular Medicine, Peking University, Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China., Zhang Y; Institute of Vascular Medicine, Peking University, Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China. Electronic address: zhangyy@bjmu.edu.cn., Nan Y; Northwest University, Xi'an 710069, China; College of Chemistry and Chemical Engineering, Xi'an Shiyou University, Xi'an 710065, China., Zhang Q; College of Chemistry and Chemical Engineering, Xi'an Shiyou University, Xi'an 710065, China., Zhang X; Faculty of Engineering and the Environment, University of Southampton, Southampton SO17 1BJ, UK., Lei J; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China., Alberts E; Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Sciences (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam University Medical Centers, Location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands., de Man A; Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Sciences (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam University Medical Centers, Location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands., Kim HK; Plant Science and Natural Products, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333BE Leiden, the Netherlands., Hsu SJ; Plant Science and Natural Products, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333BE Leiden, the Netherlands., Jia YS; Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE, Leiden, the Netherlands., Riener J; Agilent Technologies, Hewlett-Packard-Strasse 8, 76337 Waldbronn, Germany., Zheng J; Northwest University, Xi'an 710069, China., Zhang W; School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: wanbin@sjtu.edu.cn., Zheng X; First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhengxp001@mail.xjtu.edu.cn., Cai Y; School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address: yjcai@jiangnan.edu.cn., Wang M; Northwest University, Xi'an 710069, China; Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE, Leiden, the Netherlands. Electronic address: m.wang@biology.leidenuniv.nl., Fan TP; Northwest University, Xi'an 710069, China; Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK. Electronic address: tpf1000@icloud.com., Zheng X; Northwest University, Xi'an 710069, China. Electronic address: zhengxh@nwu.edu.cn.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2022 Nov; Vol. 185, pp. 106458. Date of Electronic Publication: 2022 Sep 21.
DOI: 10.1016/j.phrs.2022.106458
Abstrakt: Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×10 9 /L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO 2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.
Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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