Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT1A receptor: Insights from transcriptomics

Phytomedicine. 2021 Jan:81:153436. doi: 10.1016/j.phymed.2020.153436. Epub 2020 Dec 7.

Abstract

Background: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain.

Purpose: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE).

Study design and methods: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system.

Results: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 μg/ml.

Conclusion: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.

Keywords: 5-HT(1A) receptor; Depression; Transcriptomics; Uncaria rhynchophylla.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology*
  • Computational Biology
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / blood
  • Depression / drug therapy*
  • Depression / genetics
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology
  • Receptor, Serotonin, 5-HT1A
  • Serotonin / metabolism
  • Serotonin 5-HT1 Receptor Agonists / pharmacology*
  • Stress, Psychological
  • Uncaria / chemistry*

Substances

  • Antidepressive Agents
  • Plant Extracts
  • Serotonin 5-HT1 Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone