The protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) against CUMS-induced anxiety/depression and hippocampal transcriptome changes in rats

• Published in: Pharmacological research. Modern Chinese medicine 2023-06, Vol.7, p.100250, Article 100250
• Main Authors: Xiong, Ting-Wang, Liu, Bo, Wu, Qin, Xu, Yun-Yan, Liu, Jie, Shi, Jing-Shan
• Format: Article
• Language: English
• Subjects: Anxiety and depression; Chronic unpredictable mild stress (CUMS); Dendrobium nobile Lindl. alkaloids (DNLA); Fawn-Hooded (FH/Wjd) rats; Neurotransmitters; RNA-Seq analysis
• ISSN: 2667-1425; 2667-1425
• DOI: 10.1016/j.prmcm.2023.100250

•Fawn-Hooded (FH/Wjd) rats subjected to CUMS were susceptible to anxiety/depression.•DNLA improved CUMS-induced behavioral deficits in EPM, OPT, and FST tests.•DNLA ameliorated CUMS-induced hippocampus and cortex neuron damage in FH/Wjd rats.•DNLA reversed CUMS-induced disruption in GABA, DA, and 5-HT and the HPA axis.•RNA-Seq revealed CUMS-induced aberrant gene expression in brain and effect of DNLA. Dendrobium is the famous Chinese medicine. Dendrobium nobile Lindl. alkaloids (DNLA) is the active ingredient and has been shown to have anti-aging, anti-Alzheimer's disease, and neuroprotective properties. This study examined effect of DNLA on chronic unpredictable mild stress (CUMS)-induced anxiety and depression in Fawn-Hooded (FH/Wjd) rats, a depression model in comorbid of alcoholism. FH/Wjd rats were subjected to CUMS for 49 days, followed by treatment with DNLA (20 mg/kg/day, po) for 35 days. The anxiety/depression behaviors, Nissl bodies, neurotransmitters and hypothalamic-pituitary-adrenal axis were examined. RNA-Seq analysis was performed to explore the protection mechanisms. The CUMS-induced anxiety/depressive-like behaviors were ameliorated by DNLA in the elevated-plus-maze test, open-field test, and forced swimming test. The CUMS reduced Nissl bodies in the hippocampal CA2 region and cortex was alleviated by DNLA. CUMS disrupted 5-hydroxytryptamine, dopamine and gamma-aminobutyric acid in the brain, which were recovered by DNLA. Increases in serum adrenocorticotropic hormone and corticosterone levels were prevented by DNLA. RNA-Seq revealed CUMS-induced 1607 differentially expressed genes, which were ameliorated with DNLA treatment. KEGG showed the enrichment of Ribosome, Rap1 signaling, Tight junction, and RNA transport pathways. FH/Wjd rats were susceptible to CUMS-induced anxiety and depression. DNLA ameliorated CUMS-induced anxiety/depression behaviors and neuronal damage. Multiple mechanisms were involved in the beneficial effects of DNLA, including neurotransmitters, the hypothalamic-pituitary-adrenal axis, and the hippocampal gene expressions. [Display omitted]