Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress-induced depression-like behavior

Genes Brain Behav. 2020 Jun;19(5):e12649. doi: 10.1111/gbb.12649. Epub 2020 Mar 9.


According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of "lily disease", the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High-performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme-linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ-aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural-immunity. GABAergic and glutamatergic synapses as well as brain-derived neurotrophic factor (BDNF)/TrkB-dependent phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin-1 (mTOR1), might be the main signaling pathways underlying the multi-target therapeutic effects of LBRD against depression.

Keywords: depression; homeostasis; lily bulb and Rehmannia decoction; pharmacodynamic mechanism; traditional Chinese medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cytokines / metabolism
  • Depression / drug therapy
  • Depression / genetics*
  • Depression / metabolism
  • Lilium / chemistry
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred C57BL
  • Neurotransmitter Agents / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Rehmannia / chemistry
  • Stress, Psychological / drug therapy
  • Stress, Psychological / genetics*
  • Stress, Psychological / metabolism
  • Transcriptome*


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Neurotransmitter Agents
  • Plant Extracts