Evaluation of the anti-hypertensive effect of Tengfu Jiangya tablet by combination of UPLC-Q-exactive-MS-based metabolomics and iTRAQ-based proteomics technology

Biomed Pharmacother. 2018 Apr;100:324-334. doi: 10.1016/j.biopha.2018.02.025. Epub 2018 Feb 16.

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.

Keywords: Hypertension; Metabolomics; Proteomics; Tengfu Jiangya tablet; iTRAQ.

MeSH terms

  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Chromatography, High Pressure Liquid
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / therapeutic use*
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Male
  • Mass Spectrometry
  • Metabolome / drug effects*
  • Metabolomics / methods
  • Proteome / metabolism*
  • Proteomics / methods
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Tablets

Substances

  • Antihypertensive Agents
  • Drugs, Chinese Herbal
  • Proteome
  • Tablets
  • tengfu jiangya