Yanpeng Tian1, Feng Jiang2, Yunlun Li3, Haiqiang Jiang4, Yanjun Chu1, Lijuan Zhu5, Weixing Guo6. 1. First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China; Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China. 2. Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China. 3. First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China; Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China. Electronic address: yunlun.lee@hotmail.com. 4. Central Laboratory, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China. Electronic address: jhq12723@163.com. 5. Department of Traditional Chinese Medicine, Liaocheng Hospital of Traditional Chinese Medicine, Liaocheng 252000, Shandong,China. 6. Office of the Director, Shandong Academy of Medical Sciences, Jinan 250062, Shandong, China.
Abstract
OBJECTIVE: Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine formulation composed of Uncaria rhynchophylla and Semen raphani. It is a hospital preparation that is widely used in clinics for treating hypertension. A previous metabolomics study reported that TJT exerted a protective effect on hypertension by restoring impaired NO production, ameliorating the inflammatory state, and vascular remodeling. A clinical proteomics study also revealed five key target proteins during TJT intervention. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of TJT in treating hypertension. METHODS: Serum samples from spontaneously hypertensive rats and Wistar Kyoto rats were analyzed using ultra-high performance liquid chromatography coupled to Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS)-based metabolomics technology and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics technology. Moreover, we selected two candidate proteins and determined their expression levels in rat serum using an enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 20 potential biomarkers and 14 differential proteins in rat serum were identified. These substances were mainly involved in three biological pathways: the kallikrein-kinin pathway, the lipid metabolism pathway, and the PPARγ signaling pathway. CONCLUSIONS: The results suggested that TJT could effectively treat hypertension, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of TJT on spontaneously hypertensive rats.
OBJECTIVE: Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine formulation composed of Uncaria rhynchophylla and Semen raphani. It is a hospital preparation that is widely used in clinics for treating hypertension. A previous metabolomics study reported that TJT exerted a protective effect on hypertension by restoring impaired NO production, ameliorating the inflammatory state, and vascular remodeling. A clinical proteomics study also revealed five key target proteins during TJT intervention. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of TJT in treating hypertension. METHODS: Serum samples from spontaneously hypertensiverats and Wistar Kyoto rats were analyzed using ultra-high performance liquid chromatography coupled to Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS)-based metabolomics technology and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics technology. Moreover, we selected two candidate proteins and determined their expression levels in rat serum using an enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 20 potential biomarkers and 14 differential proteins in rat serum were identified. These substances were mainly involved in three biological pathways: the kallikrein-kinin pathway, the lipid metabolism pathway, and the PPARγ signaling pathway. CONCLUSIONS: The results suggested that TJT could effectively treat hypertension, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of TJT on spontaneously hypertensiverats.
Authors: Gaurav Baranwal; Rachel Pilla; Bethany L Goodlett; Aja K Coleman; Cristina M Arenaz; Arul Jayaraman; Joseph M Rutkowski; Robert C Alaniz; Brett M Mitchell Journal: Biomolecules Date: 2021-09-21