Investigation of peptides absorbed into blood of Colla Corii asini (E'jiao) based on cisplatin-induced anemia rat model and prediction of hematopoietic active peptide.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional medicine, Asini Corii Colla (E'jiao) demonstrates significant efficacy and a favorable safety profile in the treatment of Chemotherapy-induced anemia (CIA). However, its definitive hematopoietic constituents and pharmacodynamic mechanisms remain uncharacterized. AIM OF THE STUDY: To investigate peptides derived from E'jiao with hematopoietic activity in the cisplatin-induced anemia rat model and explore their underlying mechanisms. METHODS AND METHODS: This study established a chemically induced anemia model by injecting cisplatin. The anti-anemic efficacy of E'jiao was validated through hematological analysis. Nano-liquid chromatography-mass spectrometry (Nano LC-MS) was employed to analyze peptides absorbed into blood in rats. Combined with network pharmacology and molecular weight screening, we preliminarily identified peptides exhibiting potential hematopoietic activity. Molecular docking technology was further utilized to evaluate the binding patterns and affinity of the candidate peptides with erythropoietin (EPO). RESULTS: The results demonstrated that E'jiao significantly enhanced erythropoiesis in CIA rats. Nano LC-MS identified 35 peptides absorbed into blood from E'jiao; these bioactive peptides primarily originated from collagen type I alpha 1 chain (COL1A1) and collagen type I alpha 2 chain (COL1A2). Molecular docking analysis revealed that three peptides: GEAGPAGPAGPIGPVGAR (P-GE), GPAGPTGPVGK (P-GP), and SGQPGTVGPAGVRG (P-SG) formed stable binding configurations with the α-helical domain of EPO. The study suggests that three bioactive peptides within E'jiao may exert hematopoietic functions by stabilizing the active conformation of EPO, prolonging its plasma half-life, and enhancing its biological activity. CONCLUSION: This integrative approach combining chemotherapeutic anemia modeling, peptidomics, and molecular docking provides novel insights into the peptide-mediated hematopoietic mechanisms of E'jiao, providing evidence for elucidating the biological mechanisms by which E'jiao peptides regulate hematopoiesis and offering novel perspectives for researching active components in animal-derived medicines.