year 24, Issue 96 (12-2025)
J. Med. Plants 2025, 24(96): 37-52 |
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Research code: 4010123
Ethics code: IR.KUMS.AEC.1401.003
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Kari-Khameneh N, Shirooie S, Tarlan M, Farzaei M H. Evaluation of the antidepressant-like activity of essential oil from Citrus medica fruits (L.) in mice: Involvement of CREB and BDNF. J. Med. Plants 2025; 24 (96) :37-52
URL: http://jmp.ir/article-1-3817-en.html
URL: http://jmp.ir/article-1-3817-en.html
1- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
2- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
3- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran ,mh.farzaei@gmail.com
2- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
3- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran ,
Abstract: (362 Views)
Background: Major depressive disorder affects more than 300 million people worldwide. Citrus medica L. essential oil (CMEO), rich in terpenes such as limonene, has shown antidepressant-like effects in preclinical models, potentially through hippocampal BDNF/CREB signaling, and may offer a safer natural alternative to conventional antidepressants. Objective: This study aimed to investigate the antidepressant-like effects of CMEO on depression-like behaviors induced by lipopolysaccharide (LPS) in mice and to elucidate potential underlying mechanisms involving hippocampal BDNF/p-CREB signaling and brain nitric oxide (NO) levels. Methods: CMEO composition was characterized by gas chromatography–mass spectrometry (GC-MS). Depression-like behavior was induced by intraperitoneal LPS injection (1 mg/kg). Mice were randomly assigned to four groups: Control, LPS, CMEO 50 mg/kg + LPS, and CMEO 100 mg/kg + LPS. Behavioral assessments included the Forced Swimming Test (FST), Tail Suspension Test (TST), and Open Field Test (OFT). Biochemical analyses measured hippocampal phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF), as well as brain NO levels. Results: GC-MS identified ten CMEO constituents, with limonene as the dominant compound (93.96%). CMEO at 50 and 100 mg/kg significantly reduced immobility time in the FST and TST versus the LPS group, indicating attenuated depressive-like behavior. CMEO also restored hippocampal BDNF and p-CREB levels and significantly reduced LPS-elevated NO. Conclusion: CMEO alleviates depression-like behaviors in an LPS-induced mouse model, potentially via upregulation of hippocampal BDNF and p-CREB and reduction of NO. The high limonene content may contribute to these effects, supporting CMEO as a promising natural candidate for managing depressive disorders.
Keywords: Citrus medica, Lipopolysaccharide, Depression, cAMP response element-binding protein, Brain-Derived Neurotrophic Factor, Antidepressant-like effect
Type of Study: Research |
Subject:
Pharmacognosy & Pharmaceutics
Received: 2025/01/6 | Accepted: 2025/11/9 | Published: 2025/12/1
Received: 2025/01/6 | Accepted: 2025/11/9 | Published: 2025/12/1
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