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

阿胶低分子量肽对化疗所致骨髓抑制的补血作用:药理活性评价及体内释放活性肽的鉴定

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

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.

Conclusion

This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.

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.

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