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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 3: 493 - 507

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.03.007

Hamayou (Oviductus Ranae) protein hydrolysate ameliorates depression by regulating the mitogen-activated protein kinase pathway

  • Weijia LI ,
  • Jing LU ,
  • Chao MA ,
  • Mengmeng LIU ,
  • Ke PEI ,
  • Hongyan CHEN ,
  • Zhe LIN ,
  • Guangfu LYU
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  • 1 School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China
    2 Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China
    3 School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China
    4 Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China
    5 Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China

Received date: 2024-06-16

  Accepted date: 2024-10-08

  Online published: 2025-05-21

Supported by

Science and Technology Development Project of Jilin Province: Preparation and Evaluation of an Animal Model of Liver-depression Type Depression(20220505038ZP);Exploring the Material Basis and Action Pathway of the Antipyretic Effect of Baihu Tang based on Histologic Techniques(20240602036RC)

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Abstract

OBJECTIVE: To clarify the effect of Hamayou (Oviductus Ranae) protein hydrolysate (ORPH) on depression and its exact underlying mechanism from a new perspective.
METHODS: We used the Chronic Unpredictable Mild Stress (CUMS) method to prepare a mouse model of depression and lipopolysaccharide (LPS) to prepare a model of BV2 cellular inflammation to investigate the antidepressant effect and mechanism of action of ORPH. Behavioral changes in mice and cerebral blood flow were detected by behavioral experiments and scatter imaging. Levels of corticosterone (CORT), proinflammatory cytokines and neurotransmitter were detected by enzyme-linked immunosorbent assay. Furthermore, hematoxylin-eosin staining, Tunel staining were used to evaluate the effect of ORPH. The distribution and expression of ionized calcium bindingadaptor molecule-1 (Iba-1) in mouse hippocampal tissue and BV2 cells were detected by immunofluorescence. Mitogen-activated protein kinase (MAPK) pathway related protein expression was detected by Western blot.
RESULTS: ORPH improved depression-like behavior, ameliorated brain tissue damage and apoptosis, and inhibited microglia activation in brain tissue in mice. In addition, ORPH reduced expression of B-cell lymphoma-2 (Bcl-2)-associated X (Bax), cysteinyl aspartate specific proteinase 3 (Caspase3), cysteinyl aspartate specific proteinase 9 (Caspase9), nuclear factor- kappa B (NF-κB), phosphorylation-p38 (p-p38), phosphorylation-Jun N-terminal kinase (p-JNK) proteins, and increased expression of Bcl-2, inhibitory kappa B alpha (IκB-α), phosphorylation-extracellular regulated protein kinases 1/2 (p-ERK1/2) proteins. On the other hand, there were fewer Iba-1-positive cells, lower expression of NF-κB, p-p38, p-JNK and p-ERK1/2 proteins, and higher expression of IκB-α proteins in BV2 cells in the ORPH group. In addition, ORPH increased 5-hydroxytryptamine, norepinephrine levels and decreased CORT, interleukin-1β (IL-1β), interleukin -6 (IL-6), tumor necrosis factor-α (TNF-α) levels.
CONCLUSION: ORPH was able to improve depression-like behaviors and that it took effects by promoting cerebral blood flow, inhibition of hypothalamic-pituitary-adrenal axis overactivation, improving the structural damage of hippocampal tissues, and inhibiting the inflammatory response. ORPH can reduced neuronal damage and inhibiting apoptosis by promoting the MAPK pathway.

Key words： Hamayou (Oviductus Ranae); protein hydrolysates; depression; mitogen-activated protein kinases; apoptosis; inflammation

Cite this article

Weijia LI , Jing LU , Chao MA , Mengmeng LIU , Ke PEI , Hongyan CHEN , Zhe LIN , Guangfu LYU . Hamayou (Oviductus Ranae) protein hydrolysate ameliorates depression by regulating the mitogen-activated protein kinase pathway[J]. Journal of Traditional Chinese Medicine, 2025 , 45(3) : 493 -507 . DOI: 10.19852/j.cnki.jtcm.2025.03.007

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