4.7 Article

Iridoids from Gardeniae fructus ameliorates depression by enhancing synaptic plasticity via AMPA receptor-mTOR signaling

Journal

JOURNAL OF ETHNOPHARMACOLOGY
Volume 268, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2020.113665

Keywords

Iridoid; Antidepressant; AMPAR; mTOR; Synaptic plasticity

Funding

  1. National Natural Science Foundation of China [81873096, 81804068]
  2. Natural Science Foundation of Jiangsu Province [BK20170769]
  3. Natural science fund for colleges and universities in Jiangsu Province [17KJD360001]
  4. Blue Project of Jiangsu Province
  5. Overseas study program for excellent young and middleaged teachers and principals of universities in Jiangsu province
  6. Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine)

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The iridoids from Gardeniae fructus exert antidepressant effects by enhancing synaptic plasticity via AMPA receptor-mTOR signaling.
Ethnopharmacological relevance: Gardeniae fructus is a traditional Chinese herb which exerts antidepressant effect. However, its effective constituent and potential mechanism are still unknown. Aim of the study: To examine whether iridoids, a type of monoterpenoids from Gardeniae fructus (IGF), exerts antidepressant effect by enhancing synaptic plasticity via AMPA receptor-mTOR signaling. Materials and methods: The antidepressant effect of IGF (15 mg/kg; 30 mg/kg; 45 mg/kg) was investigated in spatial restraint stress (SRS)-induced mice. The expression levels of AMPA receptor-mTOR signaling and synaptic proteins were measured by Western blot, dendritic spine density was observed in Golgi staining. AMPA receptor (AMPAR) inhibitor NBQX and mTOR inhibitor Rapamycin were employed to determine the roles of AMPAR and mTOR signaling in IGF-induced antidepressant effects. Results: After IGF administration, the expression of the AMPA glutamate receptor Glutamate Receptor 1 (GluA1) was inhibited in SRS mice. We also observed a trend toward the up-regulation of the mammalian target of Rapamycin (mTOR) protein kinase, p70 ribosomal protein S6K (P70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). The protein levels of Synapsin-1 and PSD-95 were decreased after SRS challenge, along with declined dendritic spine density, which were all reversed with IGF treatment. Furthermore, the treatment efficacy of IGF were blocked with AMPA receptor inhibitor NBQX or mTOR inhibitor Rapamycin. Conclusion: IGF exerted antidepressive-like effects by stimulating AMPAR-mTOR signaling regulated synaptic plasticity enhancement. This work provided an important basis for developing IGF and Gardeniae fructus as potential anti-depressants.

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