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Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTongOA

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

英文摘要

Diabetic peripheral neuropathy(DPN)is a common and devastating complication of diabetes,for which effective therapies are currently lacking.Disturbed energy status plays a crucial role in DPN pathogenesis.However,the integrated profile of energy metabolism,especially the central carbohy-drate metabolism,remains unclear in DPN.Here,we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry(HPIC-MS/MS)to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats.Furthermore,JinMaiTong(JMT),a traditional Chinese medicine(TCM)formula,was found to be effective for DPN,improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration.JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions,including excessive glycolysis restoration,tricarboxylic acid cycle improvement,and increased adenosine triphosphate(ATP)generation.Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions,which was remarkably corrected by JMT treatment.In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α).Our results expand the thera-peutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs,such as JMT,as an effective strategy for its treatment.

Bingjia Zhao;Qian Zhang;Yiqian He;Weifang Cao;Wei Song;Xiaochun Liang

Department of Traditional Chinese Medicine,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,100730,ChinaInstitute of Basic Medicine Sciences,Chinese Academy of Medical Sciences,Beijing,100005,ChinaMedical Research Center,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,100730,China

Diabetic peripheral neuropathyJinMaiTongEnergy metabolismTargeted metabolomicsAdenosine monophosphate-activated protein kinase

《药物分析学报(英文)》 2024 (002)

225-243 / 19

This work was supported by the National Natural Science Foundation of China(Grant Nos.:82104827 and 82274336),the National High Level Hospital Clinical Research Funding,China(Grant No.:2022-PUMCH-A-265),and the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(Grant No.:CACM-2022-QNRC2-B14).

10.1016/j.jpha.2023.09.007

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