Research Paper Volume 12, Issue 17 pp 17436—17458

Jinmaitong ameliorates diabetic peripheral neuropathy in streptozotocin-induced diabetic rats by modulating gut microbiota and neuregulin 1

Jun Xie1, *, , Wei Song2, *, , Xiaochun Liang1, , Qian Zhang1, , Yue Shi1, , Wei Liu1, , Xiaohu Shi1, ,

  • 1 Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • 2 Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
* Equal contribution

Received: December 3, 2019       Accepted: July 6, 2020       Published: September 13, 2020
How to Cite

Copyright: © 2020 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Jinmaitong (JMT), a compound prescription of traditional Chinese medicine, has long been used as a therapy for diabetic peripheral neuropathy (DPN). However, the neuroprotective mechanisms of JMT and its effect on gut microbiota remained unknown. Here, we examined the effects of JMT on behavior, pathomorphology and gut microbiota in streptozotocin (STZ)-induced DPN rats. Compared to distilled water administration, JMT reversed decreases in mechanical withdraw threshold and intraepidermal nerve fiber density, improved neurological morphology of sciatic nerves, increased serum neuregulin 1 (NRG1) level and contactin-associated protein (Caspr)-positive paranodes, and decreased amyloid precursor protein (APP) accumulation in DPN rats. More importantly, JMT enriched nine species of the gut microbiota of DPN rats, helping to prevent dysbiosis. Among these species, p_Actinobacteria, p_Proteobacteria and c_Actinobacteria were negatively correlated with DPN phenotypes and positively correlated with serum NRG1 level. These results indicate that JMT may exert a neuroprotective effect by modulating phenotype-associated gut microbiota and increasing serum NRG1 level in STZ-induced DPN rats. JMT may therefore be an effective complementary and alternative anti-DPN therapy.


T2DM: Type 2 diabetes mellitus; DPN: Diabetic peripheral neuropathy; NTP: Neurotropin®; JMT: Jinmaitong; TCM: Traditional Chinese medicine; UPLC-QTOF-MS: Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry; PUMCH: Peking union medical college hospital; STZ: Streptozocin; NIH: National institutes of health; LEfSe: Linear discriminant analysis coupled with effect size; MWT: Mechanical withdraw threshold; PBS: Phosphate buffered saline; PFA: Paraformaldehyde; ELISA: Enzyme-linked immunosorbent assay; NRG1: Neuregulin 1; HE: Hematoxylin and eosin; TEM: Transmission electron microscope; Caspr: Contactin-associated protein; APP: Amyloid precursor protein; βIII-tubulin: Beta Tubulin 3; IENFD: Intraepidermal nerve fiber density; PGP 9.5: Protein gene product 9.5.; MBP: Myelin basic protein; P0: Myelin protein zero; MAG: Myelin-associated glycoprotein; IGF-1: Insulin-like growth factor 1.