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World J Exp Med. Sep 20, 2025; 15(3): 103154
Published online Sep 20, 2025. doi: 10.5493/wjem.v15.i3.103154
Gas chromatography-mass spectrometry-based plasma metabolomics analysis in hypertensive patients with Yin deficiency and Yang hyperactivity syndrome
Dinala Jialiken, Jing Dai, Ya-Dong Fan, Hai-Tao Zhang, Jin-Jun Shan, Wei-Chen Xu, Chong Zou
Dinala Jialiken, Jing Dai, Ya-Dong Fan, Hai-Tao Zhang, Department of Cardiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210004, Jiangsu Province, China
Jin-Jun Shan, Wei-Chen Xu, College of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing 210004, Jiangsu Province, China
Chong Zou, Department of GCP Research Center, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210004, Jiangsu Province, China
Co-first authors: Dinala Jialiken and Jing Dai.
Author contributions: Jialiken D, Dai J, and Fan YD contributed to data curation; Jialiken D and Fan YD contributed to investigation and writing of the original draft; Jialiken D, Zhang HT, and Xu WC contributed to formal analysis; Fan YD contributed to methodology; Shan JJ contributed to manuscript review & editing; Zou C contributed to supervision, funding acquisition, project administration, and manuscript review & editing.
Supported by the Projects of Design and Statistics of Clinical Trials in Traditional Chinese Medicine, No. A YXC2022-01-01 10; Exploring the Mechanism by which Pingyang Yuyin Granules Improve Hypertensive Kidney Injury Based on the 'Balance' Theory of PPARγ/HGF and TGF-β1/Smads Signaling Pathways, No. Y2022ZR09.
Institutional review board statement: The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Affiliated Hospital of Nanjing University of traditional Chinese Medicine (Approval No. 2019NL-190-02). All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki and its later amendments.
Informed consent statement: Written informed consent was obtained from all participants prior to their inclusion in the study. Participants were informed about the study objectives, procedures, potential risks, and benefits, and their right to withdraw at any time without consequences.
Conflict-of-interest statement: All authors have no competing interests to disclose.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Data sharing complies with institutional and ethical guidelines to ensure participant confidentiality.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chong Zou, PhD, Professor, Department of GCP Research Center, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Qinhuai District, Nanjing 210004, Jiangsu Province, China. yfy105@njucm.edu.cn
Received: November 11, 2024
Revised: February 28, 2025
Accepted: June 3, 2025
Published online: September 20, 2025
Processing time: 275 Days and 3.3 Hours
Abstract
BACKGROUND

Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases, stroke, and renal failure. Traditional Chinese Medicine (TCM) has been utilized for an extended period to address hypertension, with the syndrome known as Yin deficiency and Yang hyperactivity syndrome (YDYHS) frequently observed in individuals with elevated blood pressure. This syndrome is characterized by symptoms including dizziness, tinnitus, irritability, and insomnia, which are thought to result from an imbalance between Yin, representing the cooling and nourishing aspects, and Yang, denoting the active and warming aspects of the body. Despite the prevalent application of TCM in clinical settings, the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.

AIM

To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry (GC-MS) to elucidate the distinctive blood metabolite pattern in this patient population.

METHODS

GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls. Chemometric methods, including principal component analysis and partial least squares discriminant analysis, were employed to identify potential biochemical patterns. Simultaneously, the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways. Using variable importance in projection and receiver operating characteristic curve analyses, potential biomarkers were extracted to assess their clinical utility.

RESULTS

Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers (4-hydroxybenzoic acid, pectin, 1,2,3-trihydroxybenzene, D-ribose, 3-hydroxybutyric acid, quinic acid, L-lysine, oleic acid, 2-hydroxybutyric acid, linoleic acid, citric acid, alpha-tocopherol, D-glucuronic acid, glycerol, N-acetyl-L-aspartic acid, beta-mannosylglycerate, indolelactic acid, L-glutamic acid, D-maltose, L-aspartic acid) and four metabolic pathways (linoleic acid metabolism; alanine, aspartate and glutamate metabolism; D-glutamine and D-glutamate metabolism; arginine biosynthesis). The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls. The area under the curve values ranged from 0.750 to 0.866. Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.

CONCLUSION

The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group, highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients. These findings may serve as an important material basis for understanding the occurrence and development of the disease, providing a scientific foundation for future clinical diagnosis.

Keywords: Hypertension; Metabolomics; Gas chromatography-mass spectrometry; Yin deficiency and Yang hyperactivity syndrome; Syndrome differentiation

Core Tip: Metabolomic profiling of hypertensive patients with Yin deficiency and Yang hyperactivity syndrome identified 20 potential biomarkers and four metabolic pathways. These biomarkers and pathways distinguished hypertensive patients with Yin deficiency and Yang hyperactivity syndrome from healthy controls. These potential biomarkers and pathways suggest the underlying metabolic basis of Yin deficiency and Yang hyperactivity syndrome in hypertensive patients. The metabolomic profiles provide novel insights into the mechanisms of Yin deficiency and Yang hyperactivity syndrome in hypertensive patients.