Antidepressant-like Effects Of Penta-acetyl Geniposide In Chronic ...

Full text links CiteDisplay options Display options Format AbstractPubMedPMID

Abstract

We previously reported that penta-acetyl geniposide ((Ac)5GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide, a major active component of Gardenia jasminoides Ellis. This study demonstrated the antidepressant-like effects of (Ac)5GP and its involved mechanisms using a rat depression model caused by chronic unpredictable mild stress (CUMS). Behavioral tests including sucrose preference, open field and forced swimming were applied to evaluate depression symptoms. IL-1β, IL-6 and TNF-α mRNA and protein levels in prefrontal cortex (PFC) were respectively measured by quantitative PCR and ELISA. The protein levels of IκBα, p-IκBα, NF-κB p65, NLRP3, pro- and mature-IL-1β in PFC were determined by western blot. The activity of hypothalamic-pituitaryadrenal (HPA) axis was also measured. (Ac)5GP treatment alleviated the CUMS-induced depressive-like behaviors in rats, as indicated by increased sucrose intake, increased total crossing and rearing numbers, improved central activity and reduced immobility time. (Ac)5GP reversed the CUMS-induced elevations of IL-1β, IL-6 and TNF-α mRNA and protein levels in PFC. (Ac)5GP reduced degradation and phosphorylation of IκBα and protein level of nuclear NF-κB p65 in PFC. (Ac)5GP also decreased the mRNA and protein levels of NLRP3 and reduced the ratio of mature-IL-1β protein over total IL-1β protein (pro-IL-1β + mature-IL-1β) in PFC. Moreover, (Ac)5GP reduced serum levels of adrenocorticotropic hormone/corticosterone and mRNA level of hypothalamic corticotrophin-releasing hormone. In conclusion, (Ac)5GP treatment improved the depressive-like behaviors in CUMS rats perhaps by suppressing neuroinflammation in PFC and inhibiting activations of NF-κB and NLRP3 and also attenuating HPA axis hyperactivity.

Keywords: Antidepressant; Chronic unpredictable mild stress; HPA axis; NF-κB pathway; Neuroinflammation; Penta-acetyl geniposide.

Copyright © 2020 Elsevier B.V. All rights reserved.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

MeSH terms

• Animals Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Antidepressive Agents / pharmacology* Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Antidepressive Agents / therapeutic use Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Chronic Disease / psychology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Depression / drug therapy* Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Depression / etiology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Depression / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Depression / psychology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Disease Models, Animal Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Humans Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Hypothalamo-Hypophyseal System / drug effects Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Hypothalamo-Hypophyseal System / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Inflammasomes / drug effects Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Inflammasomes / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Inflammasomes / metabolism Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Iridoids / pharmacology* Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Iridoids / therapeutic use Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Male Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• NF-kappa B / metabolism Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Pituitary-Adrenal System / drug effects Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Pituitary-Adrenal System / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Prefrontal Cortex / drug effects* Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Prefrontal Cortex / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Prefrontal Cortex / pathology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Rats Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Signal Transduction / drug effects Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Signal Transduction / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Stress, Psychological / complications* Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Stress, Psychological / immunology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Stress, Psychological / psychology Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search

Substances

• Antidepressive Agents Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Inflammasomes Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Iridoids Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• NF-kappa B Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• NLR Family, Pyrin Domain-Containing 3 Protein Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• Nlrp3 protein, rat Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search
• geniposide Actions
  • Search in PubMed
  • Search in MeSH
  • Add to Search

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Ovid Technologies, Inc.

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal