Total saponins from the leaves of Panax notoginseng inhibit depression on mouse chronic unpredictable mild stress model by regulating circRNA expression

Abstract

Objectives: Total saponins from the leaves of Panax notoginseng saponins (SLPN) could inhibit development of depression, but the underlying mechanisms remains unclear. This study aimed to address the roles of circular RNAs in depression inhibition by SLPN.

Methods: The mouse chronic unpredictable mild stress (CUMS) model was established, which were confirmed by mouse weight, forced swimming test (FST) and tail suspension test (TST). Effects of SLPN on depression were evaluated in CUMS through these same assays. Circular RNA profiles in mouse ventral medial prefrontal cortex (VMPC) and hippocampus of CUMS mice were determined by high-through sequencing, followed by confirmation via qRT-PCR. Overexpression of mmu_circ_0001223 was done by transfection of PC12 cell through lentiviral system. Protein abundances of cAMP response element binding protein 1(CREB1) and brain-derived neurotrophic factor (BDNF) were evaluated by western blotting.

Results: Mouse body weight, immobility time in FST and immobility time in TST of CUMS mice were significantly recovered by SLPN treatment. A large number of circular RNAs were differentially expressed in the ventral medial prefrontal cortex (VMPC) and hippocampus tissues of CUMS mice. Among them, mmu_circ_0001223 expression was greatly decreased in CUMS mice, but significantly elevated by SLPN treatment. The protein levels of CREB1 and BDNF were also remarkably promoted in CUMS mice by treatment of SLPN. Overexpression of mmu_circ_0001223 enhanced CREB1 and BDNF protein levels in PC12 cells.

Conclusion: SLPN regulate the expression of large number circular RNAs in CUMS mice, which might be important mediators of SLPN's anti-depression effects.

Keywords: Panax notoginseng; Depression; chronic unpredictable mild stress; circRNAs; hippocampus; ventral medial prefrontal cortex.