Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics

Abstract Background TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed...

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Main Authors: Zhichao Huang, Wugang Zhang, Qiong An, Yifan Lang, Ye Liu, Huifang Fan, Haifang Chen
Format: Article
Language:English
Published: BMC 2023-02-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-023-00716-w
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author Zhichao Huang
Wugang Zhang
Qiong An
Yifan Lang
Ye Liu
Huifang Fan
Haifang Chen
author_facet Zhichao Huang
Wugang Zhang
Qiong An
Yifan Lang
Ye Liu
Huifang Fan
Haifang Chen
author_sort Zhichao Huang
collection DOAJ
description Abstract Background TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed to investigate the anti-hyperuricemia mechanism using metabolomics and confirm the active CF fraction. Methods The hyperuricemia model was established through intraperitoneal injection containing 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. We used serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, interleukin-6 (IL-6) and interleukin-1β (IL-1β) as indicators to evaluate the efficacy of CF and the four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF was considered through non-targeted metabolomics depending on the UPLC-Q-TOF–MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) helped explore the potential biomarkers in hyperuricemia. Moreover, the differential metabolites and metabolic pathways regulated by CF and four fractions were also assessed. Results CF revealed a significant anti-hyperuricemia effect by down-regulating the level of sUA, sCRE, sIL-1β, and XOD. SX, CF30, CF60, and CF90 differed in the anti-hyperuricemia effect. Only CF60 significantly lowered the sUA level among the four fractions, and it could be the main efficacy fraction of TFTS. Forty-three differential metabolites were identified in hyperuricemia rats from plasma and kidney. Pathway analysis demonstrated that seven pathways were disrupted among hyperuricemia rats. CF reversed 19 metabolites in hyperuricemia rats and exerted an anti-hyperuricemia effect by regulating purine metabolism. CF60 was the main active fraction of TFTS and exerted a similar effect of CF by regulating purine metabolism. Conclusions CF and CF60 could exert an anti-hyperuricemia effect by regulating the abnormal purine metabolism because of hyperuricemia while improving intestinal and renal function. CF60 could be the main active fraction of TFTS.
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spelling doaj.art-e0af6345fd074ea38c9d5e032559de0b2023-03-22T12:22:34ZengBMCChinese Medicine1749-85462023-02-0118111910.1186/s13020-023-00716-wExploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomicsZhichao Huang0Wugang Zhang1Qiong An2Yifan Lang3Ye Liu4Huifang Fan5Haifang Chen6Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese MedicineKey Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese MedicineKey Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese MedicineState Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese MedicineState Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese MedicineState Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese MedicineKey Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese MedicineAbstract Background TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed to investigate the anti-hyperuricemia mechanism using metabolomics and confirm the active CF fraction. Methods The hyperuricemia model was established through intraperitoneal injection containing 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. We used serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, interleukin-6 (IL-6) and interleukin-1β (IL-1β) as indicators to evaluate the efficacy of CF and the four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF was considered through non-targeted metabolomics depending on the UPLC-Q-TOF–MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) helped explore the potential biomarkers in hyperuricemia. Moreover, the differential metabolites and metabolic pathways regulated by CF and four fractions were also assessed. Results CF revealed a significant anti-hyperuricemia effect by down-regulating the level of sUA, sCRE, sIL-1β, and XOD. SX, CF30, CF60, and CF90 differed in the anti-hyperuricemia effect. Only CF60 significantly lowered the sUA level among the four fractions, and it could be the main efficacy fraction of TFTS. Forty-three differential metabolites were identified in hyperuricemia rats from plasma and kidney. Pathway analysis demonstrated that seven pathways were disrupted among hyperuricemia rats. CF reversed 19 metabolites in hyperuricemia rats and exerted an anti-hyperuricemia effect by regulating purine metabolism. CF60 was the main active fraction of TFTS and exerted a similar effect of CF by regulating purine metabolism. Conclusions CF and CF60 could exert an anti-hyperuricemia effect by regulating the abnormal purine metabolism because of hyperuricemia while improving intestinal and renal function. CF60 could be the main active fraction of TFTS.https://doi.org/10.1186/s13020-023-00716-wTFTSHyperuricemiaMetabolomicsMechanism
spellingShingle Zhichao Huang
Wugang Zhang
Qiong An
Yifan Lang
Ye Liu
Huifang Fan
Haifang Chen
Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics
Chinese Medicine
TFTS
Hyperuricemia
Metabolomics
Mechanism
title Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics
title_full Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics
title_fullStr Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics
title_full_unstemmed Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics
title_short Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics
title_sort exploration of the anti hyperuricemia effect of tongfengtangsan tfts by uplc q tof ms based non targeted metabonomics
topic TFTS
Hyperuricemia
Metabolomics
Mechanism
url https://doi.org/10.1186/s13020-023-00716-w
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