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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 4: 670 - 679

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240626.002

Original articles

Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats

  • Tongtong LIU ,
  • Xi ZHANG ,
  • Hui YANG ,
  • Xiaoyuan LIN ,
  • Jian LIU ,
  • Xiuli ZHANG ,
  • Dongwei GUO ,
  • Hongqing ZHAO ,
  • Manshu ZOU ,
  • Chang LEI ,
  • Hongping LONG ,
  • Yan LUO ,
  • Yun XIANG ,
  • Jinwen GE ,
  • Yuhong WANG ,
  • Pan MENG
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  • 1 Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
    2 the Second People's Hospital of Hunan Province, Changsha 410007, China
    3 The First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha 410007, China
    4 Hunan Academy of Chinese Medicine, Changsha 410013, China

Received date: 2023-01-12

  Accepted date: 2023-08-22

  Online published: 2024-06-26

Supported by

Outstanding Youth Project of Natural Science Foundation of Hunan Province: Mechanisms of Emotional-behavioural and Cognitive Impairment in Depression and Intervention with Traditional Chinese Medicine(2020JJ3027);Training Plan of Outstanding Innovative Youth of Changsha(kq2009018);Key Projects of Hunan Provincial Department of Education: Hspa5/PrPc-based Study on the Mechanism of Lymphoid System Damage in Cerebral Small Vessel Disease with Depression and Intervention with Traditional Chinese Medicine(23A0281);Traditional Chinese Medicine Research Program Project of Hunan Province: Mechanisms of Impairment of Ventral and Dorsal Hippocampal Differential Function in Depression based on Sonic Hedgehog/Brain-Derived Neurotrophic Factor Signalling-Mediated Synaptogenesis in Newborn Neurons and Intervention with Traditional Chinese Medicine(B2023021);Open Fund Project of State Key Laboratory of Traditional Chinese Medicine Powder and Innovative Drugs: Mechanisms of Glymphatic Iinjury in Cerebral Small Vessel Disease with Depression Based on Aquaporin Protein-4 Signalling-Mediated Astrocyte-Responsive Hyperplasia and Intervention with Traditional Chinese Medicine(23PTKF1013)

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Abstract

OBJECTIVE: To investigate the effects of luteolin on chronic unpredictable mild stress (CUMS)-induced depressive rats and corticosterone (CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the action.

METHODS: The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septo-temporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine (BrdU), the expression of BDNF, neurotrophin-3 (NT-3), and nerve growth factor (NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B (TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein (p-CREB) were detected through the high content analysis (HCA) to investigate neurotrophin and apoptosis.

RESULTS: Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen, and BrdU + doublecortin in septo-temporal axis of S2 (mid-septal) and T3 (mid-temporal). Moreover, expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neurons.

CONCLUSION: The results provided direct evidence that luteolin has an antidepressant effect and could effectively promote the regeneration of the septotemporal axis nerve and hippocampal neuronutrition, which suggested that the antidepressant effect of luteolin may be related to hippocampal neurogenesis.

Key words： luteolin; depression; chronic unpredicted mild stress; hippocampal neurogenesis; septo-temporal axis

Cite this article

Tongtong LIU , Xi ZHANG , Hui YANG , Xiaoyuan LIN , Jian LIU , Xiuli ZHANG , Dongwei GUO , Hongqing ZHAO , Manshu ZOU , Chang LEI , Hongping LONG , Yan LUO , Yun XIANG , Jinwen GE , Yuhong WANG , Pan MENG . Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 670 -679 . DOI: 10.19852/j.cnki.jtcm.20240626.002

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