Peganum harmala L. seed extract attenuates anxiety and depression in rats by reducing neuroinflammation and restoring the BDNF/TrkB signaling pathway and monoamines after exposure to chronic unpredictable mild stress
METABOLIC BRAIN DISEASE, vol.39, no.8, pp.1523-1541, 2024 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 39 Issue: 8
- Publication Date: 2024
- Doi Number: 10.1007/s11011-024-01416-6
- Journal Name: METABOLIC BRAIN DISEASE
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, MEDLINE
- Page Numbers: pp.1523-1541
- Kütahya Health Sciences University Affiliated: Yes
Abstract
Depression Depression is a
mental disorder characterised by persistent low mood, anhedonia and cognitive
impairment that affects an estimated 3.8% of the world's population, including
5% of adults. Peganum
harmala L. (P. harmala)
is a medicinal plant and has been reported to be effective against Alzheimer's
disease, Parkinson's disease and depression. The present study was aimed to
evaluate the behavioral and pharmacological effects of P. harmala seed extract in rats exposed to chronic unpredictable
mild stress (CUMS) in vivo and to investigate
the mechanism of action. CUMS-exposed rats were treated with P. harmala extract (75 and 150 mg/kg,
i.p.) for 2 weeks. HPLC analysis was used to determine
the concentration of harmaline and harmine alkaloids in the extract. Heavy metal analysis in seeds was performed
by ICP-MS. Our results showed that P. harmala at the dose of 150 mg/kg significantly reduced the depressive-like
behaviors in CUMS-exposed rats, as evidenced by increased sucrose consumption
in the sucrose preference test (SPT), decreased immobility time in the forced
swim test (FST) and plasma corticosterone levels, increased the time spent in
open arms in the elevated plus maze (EPM), and improved memory and learning in
the passive avoidance test (PAT). In addition, P. harmala decreased monoamine oxidase-A (MAO-A) levels, and
increased serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels in the
brains of rats exposed to CUMS. P.
harmala decreased the expression of the pro-inflammatory transcription
factor nuclear factor-κB (NF-κB), and increased the antioxidant nuclear factor
erythroid 2–related factor 2 (Nrf2) in rat brain. Furthermore, P. harmala improved brain-derived
neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein
expression in rat brain. In conclusion, P.
harmala at a dose of 150 mg/kg is more effective in preventing
depressive-like behavior in CUMS-exposed rats by improving neurotransmitter
levels, reducing oxidative stress, suppressing neuroinflammation and activating
the BDNF/TrkB pathway, all of which are important in the pathogenesis of
depression.
Keywords Peganum harmala L., Depression, In vivo,
Chronic unpredictable mild stress, BNDF/TrkB, Nrf2, NF-κB, HPLC, ICP-MS