Berberine attenuates depressive-like behaviors by suppressing neuro-inflammation in stressed mice

Berberine, the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects in rodents. However, it is still not clear the involvement of neuro-inflammation suppression in the effects of berberine. The purpose of this study was to determine whether berberine affects the neuro-inflammation system in mice induced by chronic unpredictable mild stress (CUMS). Berberine was orally administrated in normal or CUMS mice for successive four weeks. Behavioral evaluation showed that berberine prevented the depressive deficits both in sucrose preference test and novelty-suppressed feeding test. The elevation of hippocampal pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the activation of microglia were decreased by berberine. In addition, chronic berberine treatment inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway as the phosphorylated proteins of NF-κB, IκB kinase (IKK)α and IKKβ in the hippocampus were suppressed after berberine administration. Furthermore, inducible nitric oxide synthase (iNOS), one downstream target of NF-κB signaling pathway was also inhibited by berberine. In conclusion, these findings suggest that administration of berberine could prevent depressive-like behaviors in CUMS mice by suppressing neuro-inflammation in the hippocampus.