Protoilludane sesquiterpenoid aromatic esters from Armillaria mellea improve depressive-like behavior induced by chronic unpredictable mild stress in mice

Abstract

• To study the effect of Protoilludane sesquiterpenoid aromatic esters from A. mellea (PSAM) on CUMS-induced depression-like behavior in mice for the first time. • To study the effect of PSAM on CUMS-induced depression-like behavior in mice for the first time. • PSAM plays an antidepressant role by regulating inflammation activation, synaptic deficits and neuronal apoptosis. • PSAM could be used as a potential material for anti-inflammatory functional food supplements. This study mainly explored the antidepressant-like effects and mechanisms of protoilludane sesquiterpenoid aromatic esters from Armillaria mellea (PSAM) in depressive mice induced by chronic unpredictable mild stress (CUMS). The results demonstrated that PSAM exerted antidepressant-like effects in mice, as indicated by reversing CUMS-induced changes in body weight gain, sucrose preference, and behavior in the open field test, elevated plus maze test, tail suspension test and forced swimming test. Meanwhile, PSAM inhibited the release of hippocampus IL-6, IL-1β and TNF-α levels, and down-regulated hippocampus caspase-9 and NLRP3 levels, but improved serum CORT and ACTH levels and hypothalamic CRH level, and up-regulated hippocampus BDNF, p-CREB and PSD95 levels and hypothalamic GR level, suggesting that the antidepressant-like effects of PSAM were related to its inhibition of neuroinflammation, apoptosis and HPA axis hyperactivity, and improvement of synaptic plasticity and function. This study provided a basis for PSAM as functional health foods for antidepressants.