A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy

Jin-Mai-Tong (JMT) decoction is a traditional Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study is to investigate the neuroprotective effect of JMT decoction on diabetic rats with peripheral neuropathy and to elucidate the potential mechanism base...

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Main Authors: Qian Zhang, Wei Song, Xiaochun Liang, Jun Xie, Yue Shi, Xiaohu Shi, Bintao Qiu, Xiuting Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.00221/full
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author Qian Zhang
Wei Song
Xiaochun Liang
Jun Xie
Yue Shi
Xiaohu Shi
Bintao Qiu
Xiuting Chen
author_facet Qian Zhang
Wei Song
Xiaochun Liang
Jun Xie
Yue Shi
Xiaohu Shi
Bintao Qiu
Xiuting Chen
author_sort Qian Zhang
collection DOAJ
description Jin-Mai-Tong (JMT) decoction is a traditional Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study is to investigate the neuroprotective effect of JMT decoction on diabetic rats with peripheral neuropathy and to elucidate the potential mechanism based on a metabolomics approach. Sprague-Dawley (SD) rats were randomly divided into four groups: control group, Streptozotocin (STZ) induced model group, JMT low dose (JMT-L) treated group and JMT high dose (JMT-H) treated group. After 12 weeks of treatment, behavioral changes, small fiber loss, and histopathological damages of sciatic nerves were estimated. Serum samples were collected for untargeted metabolomics analysis based on UPLC/QTOF-MS and multivariate statistics. As a result, JMT treatment at two dosages (13.9 and 27.8 g/kg⋅d) evidently improved the mechanical pain threshold (P < 0.05), increased the intraepidermal nerve fiber density (IENFD) and subepidermal nerve fiber density (SNFD) (P < 0.05), and renovated the demyelination and axonal atrophy of sciatic nerves on DPN rats. Furthermore, metabolomics study revealed that the serum metabolic profiles altered significantly among the control group and the STZ-induced model group. A total of 21 metabolites were identified as potential biomarkers related to the therapeutic effect of JMT decoction. Among them, 16 biomarkers were found in both JMT-H and JMT-L treated groups, while the five others were specific to JMT-H group. These metabolites mainly involved in lipid metabolism, tricarboxylic acid (TCA) cycle, amino acid metabolism, and so on. Besides, correlation analysis indicated that both mechanical pain threshold and distal nerve fiber density were negatively correlated with the serum levels of metabolites from lipid metabolism and TCA cycle. In conclusion, the results demonstrated that JMT decoction has an obvious protective effect against DPN, which could be mediated via ameliorating the metabolic disorders in diabetic rats with peripheral neuropathy.
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spelling doaj.art-263858849e91462080c4d59c716b95cf2022-12-21T18:13:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-03-011110.3389/fphar.2020.00221512843A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics StrategyQian Zhang0Wei Song1Xiaochun Liang2Jun Xie3Yue Shi4Xiaohu Shi5Bintao Qiu6Xiuting Chen7Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaMedical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaMedical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaMedical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaJin-Mai-Tong (JMT) decoction is a traditional Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study is to investigate the neuroprotective effect of JMT decoction on diabetic rats with peripheral neuropathy and to elucidate the potential mechanism based on a metabolomics approach. Sprague-Dawley (SD) rats were randomly divided into four groups: control group, Streptozotocin (STZ) induced model group, JMT low dose (JMT-L) treated group and JMT high dose (JMT-H) treated group. After 12 weeks of treatment, behavioral changes, small fiber loss, and histopathological damages of sciatic nerves were estimated. Serum samples were collected for untargeted metabolomics analysis based on UPLC/QTOF-MS and multivariate statistics. As a result, JMT treatment at two dosages (13.9 and 27.8 g/kg⋅d) evidently improved the mechanical pain threshold (P < 0.05), increased the intraepidermal nerve fiber density (IENFD) and subepidermal nerve fiber density (SNFD) (P < 0.05), and renovated the demyelination and axonal atrophy of sciatic nerves on DPN rats. Furthermore, metabolomics study revealed that the serum metabolic profiles altered significantly among the control group and the STZ-induced model group. A total of 21 metabolites were identified as potential biomarkers related to the therapeutic effect of JMT decoction. Among them, 16 biomarkers were found in both JMT-H and JMT-L treated groups, while the five others were specific to JMT-H group. These metabolites mainly involved in lipid metabolism, tricarboxylic acid (TCA) cycle, amino acid metabolism, and so on. Besides, correlation analysis indicated that both mechanical pain threshold and distal nerve fiber density were negatively correlated with the serum levels of metabolites from lipid metabolism and TCA cycle. In conclusion, the results demonstrated that JMT decoction has an obvious protective effect against DPN, which could be mediated via ameliorating the metabolic disorders in diabetic rats with peripheral neuropathy.https://www.frontiersin.org/article/10.3389/fphar.2020.00221/fulldiabetic peripheral neuropathyTraditional Chinese MedicineJin-Mai-Tong decoctionmetabolomicsdiabetes
spellingShingle Qian Zhang
Wei Song
Xiaochun Liang
Jun Xie
Yue Shi
Xiaohu Shi
Bintao Qiu
Xiuting Chen
A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
Frontiers in Pharmacology
diabetic peripheral neuropathy
Traditional Chinese Medicine
Jin-Mai-Tong decoction
metabolomics
diabetes
title A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
title_full A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
title_fullStr A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
title_full_unstemmed A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
title_short A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
title_sort metabolic insight into the neuroprotective effect of jin mai tong jmt decoction on diabetic rats with peripheral neuropathy using untargeted metabolomics strategy
topic diabetic peripheral neuropathy
Traditional Chinese Medicine
Jin-Mai-Tong decoction
metabolomics
diabetes
url https://www.frontiersin.org/article/10.3389/fphar.2020.00221/full
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