Frontiers in Pharmacology (Jun 2024)

Blood-supplementing effect of low molecular weight peptides of E-Jiao on chemotherapy-induced myelosuppression: evaluation of pharmacological activity and identification of bioactive peptides released in vivo

  • Jinju Zhang,
  • Jinju Zhang,
  • Danlin Lin,
  • Danlin Lin,
  • Yuting Wu,
  • Yuting Wu,
  • Lixia Chen,
  • Lixia Chen,
  • Zhiguo Ma,
  • Zhiguo Ma,
  • Zhiguo Ma,
  • Menghua Wu,
  • Menghua Wu,
  • Menghua Wu,
  • Xindan Liu,
  • Ying Zhang,
  • Ying Zhang,
  • Ying Zhang,
  • Hui Cao,
  • Hui Cao,
  • Hui Cao

DOI
https://doi.org/10.3389/fphar.2024.1366407
Journal volume & issue
Vol. 15

Abstract

Read online

Background:Equus asinus L. [Equidae; Asini Corri Colla] (donkey-hide gelatin, E-Jiao) is a traditional Chinese medicine renowned for its exceptional blood-supplementing effect. However, the specific components that contribute to its efficacy remain elusive. This study aimed to demonstrate that peptides are responsible for E-Jiao’s blood-supplementing effect and to explore the specific peptides contributing to its efficacy.Methods: The low molecular weight peptides of E-Jiao (LMEJ) were obtained using an in vitro digestion method. LMEJ and peptides in the rat bloodstream were characterized by peptidomics analysis. The blood-supplementing effect of LMEJ was assessed using blood-deficient zebrafish and mouse models. The effect of the peptides detected in rat blood was evaluated using the same zebrafish model, and network pharmacology analysis was performed to investigate the underlying mechanisms.Results: A total of 660 unique peptides were identified within LMEJ. Both E-Jiao and LMEJ significantly alleviated myelosuppression in mice but only LMEJ attenuated myelosuppression in zebrafish. After the administration of E-Jiao to rats, 67 E-Jiao-derived peptides were detected in the bloodstream, 41 of which were identical to those identified in LMEJ. Out of these 41 peptides, five were synthesized. Subsequent verification of their effects revealed that two of them were able to alleviate myelosuppression in zebrafish. Network pharmacology study suggested that E-Jiao may exert a blood-supplementing effect by regulating signaling pathways such as JAK-STAT, IL-17 and others. These results indicated that peptides are at least partially responsible for E-Jiao’s efficacy.Conclusion: This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.

Keywords