ABSTRACT
The present study aims to investigate the mechanism of Geniposide in the treatment of depression. By screening the effective components and targets of Zhi-zi-chi decoction, 140 candidate targets related to depression were identified. Further transcriptome sequencing was conducted to screen differentially expressed mRNAs and lncRNAs; 7 candidate Geniposide treatment targets for depression were obtained. KEGG/GO enrichment analysis and molecular docking were performed to select the optimal drug target, revealing that Creb1 is an important target. Additionally, Six3os1 is the lncRNA with the smallest P-value among the differentially expressed lncRNAs, and the JASPAR database revealed a binding site between Creb1 and the Six3os1 promoter. The intersection of Synapse-related genes obtained from the GeneCards database and differentially expressed mRNAs produced 6 synaptic-related genes. RNA-protein interaction prediction revealed that Six3os1 interacts with the protein encoded by these genes. Geniposide upregulates the expression of Creb1 and Six3os1. Creb1 can transcriptionally activate Six3os1, thereby upregulating the expression of the synaptic-related proteins Htr3a and Htr2a, improving depression.
Subject(s)
Drugs, Chinese Herbal , RNA, Long Noncoding , Molecular Docking Simulation , RNA, Long Noncoding/genetics , Depression/drug therapy , Depression/genetics , Drugs, Chinese Herbal/chemistryABSTRACT
Evidence exists suggesting the anti-depressive activities of geniposide (GP), a major compound in Gardenia jasminoides Ellis. Accordingly, the present study attempts to explore the anti-depressive mechanism of GP in chronic unpredictable mild stress (CUMS)-induced depression-like behaviors of mice. CUMS-induced mice were given GP daily and subjected to behavioral tests to observe the effect of GP on the depression-like behaviors. It was noted that GP administration reduced depression-like behaviors in CUMS mice. Transcriptome sequencing was conducted in three control and three CUMS mice. Differentially expressed circRNAs, lncRNAs and mRNAs were then screened by bioinformatics analyses. Intersection analysis of the transcriptome sequencing results with the bioinformatics analysis results was followed to identify the candidate targets. We found that Gata2 alleviated depression-like behaviors via the metabolism- and synapse-related pathways. Gata2 was a target of miR-25-3p, which had binding sites to circ_0008405 and Oip5os1. circ_0008405 and Oip5os1 competitively bound to miR-25-3p to release the expression of Gata2. GP administration ameliorated depression-like behaviors in CUMS mice through regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks. Taken together, GP may exert a potential antidepressant-like effect on CUMS mice, which is ascribed to regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks.
Subject(s)
Depressive Disorder , MicroRNAs , Animals , Mice , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/drug therapy , Depression/metabolism , Depressive Disorder/drug therapy , GATA2 Transcription Factor , MicroRNAs/drug effects , MicroRNAs/metabolism , RNA, Circular/drug effects , RNA, Long NoncodingABSTRACT
The non-motor symptoms (NMS) of Parkinson's disease (PD) are found in more than 90% of patients with PD. Here, we explored the effects of electroacupuncture (EA) stimulation at Zhong wan (CV-12), Qihai (RN-7), Zusanli (ST-36) and Taichong (LR-3) on NMS and brain-gut peptides of PD. We found that EA intervention alleviated the motor deficit induced by 6-OHDA in rats indicated by the decreased abnormal involuntary movements (AIMs) scores and the net number of rotations and increased cylinder test grade. It also improved the spatial memory and attenuated anxiety-like and depression of PD model rats. EA treatment significantly inhibited neuronal apoptosis in PD model animals, as demonstrated by the increased number of TH positive cells and reduced number of apoptotic cells in the substantia nigra. The expression of cleaved caspase-3 and cleaved PARP in PD model rats was markedly suppressed by EA stimulation. Moreover, EA remarkably inhibited the inflammatory response in PD model rats, as revealed by the decreased levels of TNF-α, IL-1ß, and COX-2 mRNA expression. It also attenuated the oxidative stress in rats, as indicated by the increased levels of SOD and GSH and the decreased level of MDA. EA treatment contributed to alleviating PD by regulating brain-gut peptides in rats, such as NPY, CCK, SST, GAS, and PYY. In conclusion, EA stimulation at CV-12, RN-7, ST-36, and LR-3 effectively alleviates the NMS of PD partly through regulating the levels of brain-gut peptides.
Subject(s)
Brain/metabolism , Electroacupuncture , Gene Expression Regulation , Neuropeptides/genetics , Neuropeptides/metabolism , Parkinson Disease/genetics , Parkinson Disease/therapy , Animals , Anxiety , Disease Models, Animal , Dyskinesias , Male , Oxidative Stress , Parkinson Disease/metabolism , Parkinson Disease/psychology , Rats, Sprague-Dawley , Spatial MemoryABSTRACT
It has been shown in previous studies that the autonomic nervous system can be affected by acupuncture. Within this study, teleacupuncture between China and Austria is used for quantifying the effects of heart rate (HR) and heart rate variability (HRV) in 33 Chinese patients (27 females, 6 males; mean age ± SD 49.5 ± 13.1 years; range 22-72 years) suffering from depression. Electrocardiographic signals before, during, and after acupuncture at the acupoint Baihui (GV20) were recorded in Harbin and analyzed in Graz using teleacupuncture. HRV data were analyzed in the time and frequency domain. Mean HR decreased significantly (P < 0.05) during and after acupuncture, whereas total HRV increased significantly after the third acupuncture stimulation period (P < 0.05) and also 5-10 minutes after (P < 0.05) acupuncture. The study shows that HRV could be a useful parameter for quantifying clinical effects of acupuncture on the autonomic nervous system.