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.
Highlights
Renal fibrosis (RF) is a common pathological characteristic of chronic kidney disease (CKD), which leads to final-stage renal disease (Hu et al, 2018; Yin et al, 2018; Kakitapalli et al, 2020; RayegoMateos and Valdivielso, 2020; Zeeh, 2020)
Our results showed that TFN could effectively reduce the tumor necrosis factor-α (TNF-α) and IL-1β activity and increase the superoxide dismutase (SOD) activity of rats caused by ureteral obstruction (UUO) for enhancing the antioxidant capacity, repairing damaged renal tubular epithelial cells to alleviate the process of renal interstitial fibrosis
The results show that 3-Hydroxyanthranilic acid (3-HAA) has an immunomodulatory effect, which may be due to the inhibition of PI3K/Akt/mTOR and NF-κB activation, thereby reducing the production of proinflammatory mediators in tryptophan metabolism (Krause et al, 2011)
Summary
Renal fibrosis (RF) is a common pathological characteristic of chronic kidney disease (CKD), which leads to final-stage renal disease (Hu et al, 2018; Yin et al, 2018; Kakitapalli et al, 2020; RayegoMateos and Valdivielso, 2020; Zeeh, 2020). Renal biopsies and conventional biochemical detection are commonly applied to appraise the degree of RF. They are invasive, of high cost, and unstable and even have severe side-effects, which make accurate and repeated monitoring difficult in patients in the early stage (Jenkins et al, 2011; Chen et al, 2019). The common clinical treatment for RF, that is, to dilate the renal artery to increase the systemic blood perfusion, improve microcirculation disorder to enhance metabolism, alleviate the disorder of internal environment caused by hypoxia, and reduce toxic symptoms, is not ideal for patients (Boor et al, 2010; Zhang et al, 2018; RayegoMateos and Valdivielso, 2020)
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