Arjunolic acid ameliorates lipopolysaccharide-induced depressive behavior by inhibiting neuroinflammation via microglial SIRT1/AMPK/Notch1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation is involved in the pathogenesis of depression disorder by activating microglia cells, increasing proinflammatory cytokines, effecting serotonin synthesis and metabolism, and neuronal apoptosis and neurogenesis. Arjunolic acid (ARG) is a triterpenoid derived from the fruits of Akebia trifoliata for treating psychiatric disorders in TCM clinic, which exhibits anti-inflammatory and neuroprotective effects. However, its anti-depressive effect and underlying mechanism are unknown. AIM OF THE STUDY: The aim of this study is to explore the effect of arjunolic acid on depression and its possible mechanisms. METHODS: Intraperitoneal injection of LPS in mice and LPS stimulated-BV2 microglia were utilized to set up in vivo and in vitro models. Behavioral tests, H&E staining and ELISA were employed to evaluate the effect of arjunolic acid on depression. RT-qPCR, immunofluorescence, molecular docking and Western blot were performed to elucidate the molecular mechanisms. RESULTS: Arjunolic acid dramatically ameliorated depressive behavior in LPS-induced mice. The levels of BDNF and 5-HT in the hippocampus of the mice were increased, while the number of iNOS + IBA1+ cells in the brain were decreased and Arg1+IBA1+ positive cells were increased after arjunolic acid treatment. In addition, arjunolic acid promoted the polarization of BV2 microglia from M1 to M2 type. Notably, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking technologies identified SIRT1 as the target of arjunolic acid. Moreover, after SIRT1 inhibition by using EX-527, the effects of arjunolic acid on ameliorating LPS-induced depressive behavior in mice and promoting M2 Microglia polarization were blocked. In addition, arjunolic acid activated AMPK and decreased Notch1 expression, however, inhibition of AMPK, the effect of arjunolic acid on the downregulation of Notch1 expression were weaken. CONCLUSIONS: This study elucidates that arjunolic acid suppressed neuroinflammation through modulating the SIRT1/AMPK/Notch1 signaling pathway. Our study demonstrates that arjunolic acid might serve as a potiential anti-depressant.

Performance and microbial community dynamics in anaerobic co-digestion of chicken manure and corn stover with different modification methods and trace element supplementation strategy.

The performance and microbial community dynamics in anaerobic co-digestion (ACoD) of chicken manure and corn stover with different modification methods and trace element supplementation strategy were investigated in this study. KOH and liquid fraction of digestate (LFD) were applied for modification; Fe, Co, Mn, Mo, and Ni were used for supplement. Results showed that the selected trace element was insufficient in the partial or whole digestion process. When trace element supplement was combined with KOH or LFD modifications, the ACoD obtained biomethane yields of 245.3-258.0 and 254.0-261.8 mLN·gVS-1, 26.0%-32.5% and 30.5%-34.5% more than that of the control, respectively. Microbial community analyses indicated that the composition and diversity of archaea and bacteria varied at genus level. Main pathways involved in ACoD were affected accordingly, which in turn affected co-digestion performance. This study demonstrated that the combining modification and trace element supplement could improve the digestion performance and achieve higher biomethane yield.