Dissecting Efficacy and Metabolic Characteristic Mechanism of Taxifolin on Renal Fibrosis by Multivariate Approach and Ultra-Performance Liquid Chromatography Coupled With Mass Spectrometry-Based Metabolomics Strategy

Front Pharmacol. 2021 Jan 14:11:608511. doi: 10.3389/fphar.2020.608511. eCollection 2020.

Abstract

Taxifolin (TFN) is an important natural compound with antifibrotic activity; however, its pharmacological mechanism is not clear. In this study, our aim is to gain insight into the effects of TFN and its potential mechanisms in unilateral ureteral obstruction (UUO) animal model using metabolomics approach to identify the metabolic biomarkers and perturbed pathways. Serum metabolomics analysis by UPLC-Q-TOF/MS was carried out to discover the changes in the metabolic profile. It showed that TFN has a significant protective effect on UUO-induced renal fibrosis and a total of 32 potential biomarkers were identified and related to RF progression. Of note, 27 biomarkers were regulated by TFN treatment, which participate in eight metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, and phenylalanine metabolism. It also showed that metabolomics was a promising strategy to better dissect metabolic characteristics and pharmacological mechanisms of natural compounds by multivariate approach and ultra-performance liquid chromatography coupled with mass spectrometry.

Keywords: UPLC-Q-TOF/MS; biomarker; metabolic pathway; metabolomics; natural product; renal fibrosis.