A rich component of Fructus Aurantii, meranzin hydrate, exerts antidepressant effects via suppressing caspase4 to regulate glial cell and neuronal functions in the hippocampus.

Abstract

Fructus Aurantii, a Chinese herbal medicine, has been indicated to have antidepressant effects in our previous study. However, the main component and specific mechanisms of the antidepressant effects of Fructus Aurantii still need to be further revealed. This study aimed to explore the main antidepressant component of Fructus Aurantii and the underlying mechanisms of its antidepressant effects in the hippocampus. The results showed that the component of meranzin hydrate (MH) was enrichment in Fructus Aurantii. MH could alleviate depressive phenotypes in LPS-induced mice after a single administration 1 day later. High genetic and proteinic levels of caspase4 in the hippocampus in LPS-induced mice were reversed by MH after a single administration 1 day later. Moreover, MH was capable of relieving inflammatory factors (TNF-a and IL-1β) and LPS in the serum in LPS-induced mice. Subsequently, activation of hippocampal caspase4 blocked MH's antidepressant effects and its effects on suppression of microglia and improvement of astrocyte in the hippocampus. Furthermore, MH could increase long-term potential (LTP) in the hippocampal dentate gyrus (DG) and activation of hippocampal caspase4 blocked MH's enhancement on neuronal activities and synaptic plasticity in the hippocampal DG. To sum up, the antidepressant effects of a rich component MH in Fructus Aurantii suppressed the activation of caspase4 by maintaining glial cells function to promote neuronal activities and synaptic plasticity in the hippocampus.