Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement

Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity wa...

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Main Authors: Tianyao Zheng, Shulan Su, Xinxin Dai, Liwen Zhang, Jin-Ao Duan, Zhen Ou-Yang
Format: Article
Language:English
Published: MDPI AG 2018-06-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/23/6/1490
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author Tianyao Zheng
Shulan Su
Xinxin Dai
Liwen Zhang
Jin-Ao Duan
Zhen Ou-Yang
author_facet Tianyao Zheng
Shulan Su
Xinxin Dai
Liwen Zhang
Jin-Ao Duan
Zhen Ou-Yang
author_sort Tianyao Zheng
collection DOAJ
description Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity was evaluated by body weight, paw thickness, histological changes and index of paws oedema and spleen. Serum samples were collected for estimation of biochemical indicators and cytokines. In addition, a metabonomic method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of SE by serum and urine. Multivariate statistical approaches, such as partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were built to evaluate the therapeutic effects of SE and find potential biomarkers and metabolic pathways. Administration with SE significantly ameliorated the AA severity, including body weight loss, paw swelling, histological changes and the levels of biochemical index. 33 endogenous metabolites had been identified (10 in serum and 23 in urine) in the AA rats. Urinary and serum metabolic profiling revealed that the metabolites underpin the metabolic pathway including nicotinate and nicotinamide metabolism; pentose and glucuronate interconversions; TCA cycle; beta-Alanine metabolism; purine metabolism and glycolysis or gluconeogenesis. The altered metabolites could be regulated closer to normal level after SE intervention. The results suggested SE possesses substantial anti-arthritic activity and demonstrated that metabonomics is a powerful tool to gain insight in the mechanism of SE formula in therapy.
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spelling doaj.art-8245aa5b992641d092da30c6f16604552022-12-22T02:17:22ZengMDPI AGMolecules1420-30492018-06-01236149010.3390/molecules23061490molecules23061490Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm ExcrementTianyao Zheng0Shulan Su1Xinxin Dai2Liwen Zhang3Jin-Ao Duan4Zhen Ou-Yang5Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Jiangsu University, Zhenjiang 212013, ChinaSilkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity was evaluated by body weight, paw thickness, histological changes and index of paws oedema and spleen. Serum samples were collected for estimation of biochemical indicators and cytokines. In addition, a metabonomic method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of SE by serum and urine. Multivariate statistical approaches, such as partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were built to evaluate the therapeutic effects of SE and find potential biomarkers and metabolic pathways. Administration with SE significantly ameliorated the AA severity, including body weight loss, paw swelling, histological changes and the levels of biochemical index. 33 endogenous metabolites had been identified (10 in serum and 23 in urine) in the AA rats. Urinary and serum metabolic profiling revealed that the metabolites underpin the metabolic pathway including nicotinate and nicotinamide metabolism; pentose and glucuronate interconversions; TCA cycle; beta-Alanine metabolism; purine metabolism and glycolysis or gluconeogenesis. The altered metabolites could be regulated closer to normal level after SE intervention. The results suggested SE possesses substantial anti-arthritic activity and demonstrated that metabonomics is a powerful tool to gain insight in the mechanism of SE formula in therapy.http://www.mdpi.com/1420-3049/23/6/1490silkworm excrementrheumatoid arthritisbiomarkermetabolomics
spellingShingle Tianyao Zheng
Shulan Su
Xinxin Dai
Liwen Zhang
Jin-Ao Duan
Zhen Ou-Yang
Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
Molecules
silkworm excrement
rheumatoid arthritis
biomarker
metabolomics
title Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
title_full Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
title_fullStr Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
title_full_unstemmed Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
title_short Metabolomic Analysis of Biochemical Changes in the Serum and Urine of Freund’s Adjuvant-Induced Arthritis in Rats after Treatment with Silkworm Excrement
title_sort metabolomic analysis of biochemical changes in the serum and urine of freund s adjuvant induced arthritis in rats after treatment with silkworm excrement
topic silkworm excrement
rheumatoid arthritis
biomarker
metabolomics
url http://www.mdpi.com/1420-3049/23/6/1490
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