1. Academic Validation
  2. Ameliorative effect of Gastrodia elata Blume extracts on depression in zebrafish and cellular models through modulating reticulon 4 receptors and apoptosis

Ameliorative effect of Gastrodia elata Blume extracts on depression in zebrafish and cellular models through modulating reticulon 4 receptors and apoptosis

  • J Ethnopharmacol. 2022 May 10;289:115018. doi: 10.1016/j.jep.2022.115018.
Rongchun Wang 1 Qingyu Ren 2 Daili Gao 3 Yam Nath Paudel 4 Xia Li 5 Lizhen Wang 6 Pengyu Zhang 7 Baokun Wang 8 Xueliang Shang 9 Meng Jin 10
Affiliations

Affiliations

  • 1 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: 1wangrongchun@163.com.
  • 2 School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tang'shan, 063210, Hebei Province, PR China; Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: RQY718374269@163.com.
  • 3 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: gaodaili1997@163.com.
  • 4 Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, 47500, Selangor, Malaysia. Electronic address: yam.paudel@monash.edu.
  • 5 Mills Institute for Personalized Cancer Care, Fynn Biotechnologies Ltd, Gangxing 3rd Rd, High-Tech and Innovation Zone, Bldg. 2, Rm. 2201, Ji'nan, 250101, Shandong Province, PR China. Electronic address: xialee1985@gmail.com.
  • 6 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: wlzh1106@126.com.
  • 7 School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tang'shan, 063210, Hebei Province, PR China; Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: Zpy961120@163.com.
  • 8 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: wbaokun0608@163.com.
  • 9 School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tang'shan, 063210, Hebei Province, PR China. Electronic address: shangxuelianghao@126.com.
  • 10 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address: mjin1985@hotmail.com.
Abstract

Ethnopharmacological relevance: Gastrodia elata Blume (G. elata), a traditional Chinese herb, known as "Tian Ma", is widely used as a common medicine and diet ingredient for treating or preventing neurological disorders for thousands of years in China. However, the anti-depressant effect of G. elata and the underlying mechanism have not been fully evaluated.

Aim of the study: The study is aimed to investigate the anti-depressant effect and the molecular mechanism of G. elata in vitro and in vivo using PC12 cells and zebrafish model, respectively.

Material and methods: Network pharmacology was performed to explore the potential active ingredients and action targets of G. elata Blume extracts (GBE) against depression. The cell viability and proliferation were determined by MTT and EdU assay, respectively. TUNEL assay was used to examine the anti-apoptotic effect of GBE. Immunofluorescence and Western blot were used to detect the protein expression level. In addition, novel tank diving test was used to investigate the anti-depressant effect in zebrafish depression model. RT-PCR was used to analyze the mRNA expression levels of genes.

Results: G. elata against depression on the reticulon 4 receptors (RTN4R) and apoptosis-related targets, which were predicted by network pharmacology. Furthermore, GBE enhanced cell viability and inhibited the Apoptosis in PC12 cells against CORT treatment. GBE relieved depression-like symptoms in adult zebrafish, included increase of exploratory behavior and regulation of depression related genes. Mechanism studies showed that the GBE inhibited the expression of RTN4R-related and apoptosis-related genes.

Conclusion: Our studies show the ameliorative effect of G. elata against depression. The mechanism may be associated with the inhibition of RTN4R-related and Apoptosis pathways.

Keywords

Anti-depressant activity; Network pharmacology; Neuropsychic diseases; PC12; Zebrafish.

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