ABSTRACT
INTRODUCTION: Degraded porphyran is a bioactive polysaccharide extracted from Porphyra haitanensis (P. haitanensis). According to the previous studies, it produced anti-inflammatory activity, but little is known about its effects on depression. METHODS AND RESULTS: As inflammation is one of the critical factors involved in the development of depression, this study aims to elucidate the potential antidepressant-like effects of degraded porphyran. The results show that acute porphyran treatment decreased the immobility time in despair tests. In addition, subchronic porphyran administration reverses depressive-like behaviors in lipopolysaccharide (LPS)-treated mice. Meanwhile, porphyran inhibits NF-κB/NLRP3 signaling, proinflammatory cytokine release, and microglial activation in the hippocampus. Moreover, chronic porphyran treatment activates hippocampal brain derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway in chronic unpredictable mild stress (CUMS) in mice. As a result, neurogenesis and spinogenesis are maintained. CONCLUSIONS: The findings of the present study indicate that degraded porphyran intake provides a potential strategy for depression treatment, which is mediated by the inhibition of neuroinflammation and the enhancement of neurogenesis and spinogenesis in the central nervous systems.
Subject(s)
Antidepressive Agents/pharmacology , Porphyra/chemistry , Sepharose/analogs & derivatives , Animals , Brain-Derived Neurotrophic Factor/physiology , Male , Mice , Mice, Inbred C57BL , Microglia/drug effects , Molecular Docking Simulation , Neurogenesis/drug effects , Neuroinflammatory Diseases/drug therapy , Sepharose/pharmacology , Toll-Like Receptor 4/physiologyABSTRACT
Ethnopharmacological relevance Paeonia lactiflora is a famous Traditional Chinese medicine widely used for immunological regulation. Paeoniflorin, the main component of Paeonia lactiflora, exerts neuroprotective and antidepressant-like effects in rodents. AIM OF THE STUDY: Fibroblast growth factor 2 (FGF-2) is essentially required in the central nervous system as it acts as both a neurotrophic factor and an anti-inflammatory factor participating in the regulation of proliferation, differentiation and apoptosis of neurons in the brain. However, it is unclear whether paeoniflorin could exert antidepressant effects via regulating FGF-2. MATERIALS AND METHODS: In the present study, the effects of paeoniflorin were evaluated in depressive mice induced by the endotoxin lipopolysaccharide (LPS) injection. RESULTS: The results showed that paeoniflorin markedly increased sucrose preference and reduced immobility time in LPS mice, indicating antidepressant effects. Consistent with the results from molecular docking showing paeoniflorin antagonizes TLR4, NF-κB and NLRP3, the biochemical analysis also indicated paeoniflorin inhibited TLR4/NF-κB/NLRP3 signaling, decreased proinflammatory cytokine levels and microglial activation in the hippocampus of LPS induced mice. In addition, the levels of neuronal FGF-2 and the density of dendritic spine were improved by paeoniflorin. More importantly, the FGFR1 inhibitor SU5402 prevented the antidepressant effects of paeoniflorin and blocked the neuroinflammatory and neurogenic regulatory effects of paeoniflorin, indicating that FGF-2/FGFR1 activation was required for the effects of paeoniflorin. CONCLUSION: Taken together, the results demonstrate that paeoniflorin exhibits neuroprotective and antidepressant effects in mice, which may be mediated by activating neuronal FGF-2/FGFR1 signaling via the inhibition of microglial activation in the hippocampus.
