Depression is an
inflammation-associated disease that results in major depression as
inflammation increases and progresses.
Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and anti-inflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of
connexin43 (
Cx43)
ubiquitin degradation, while Rg1 could upregulate
Cx43 expression to attenuate depression. However, whether the ubiquitination of
Cx43 is the specific correlation between depression and
inflammation, and how Rg1 ameliorates
neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (
CUS). Moreover, these
CUS rats treated with Rg1 exhibited attenuated
neuroinflammation, together with the suppression of
Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory
cytokines and the ubiquitination of
Cx43 in
lipopolysaccharide-induced glial cells. Furthermore, treatment with
ubiquitin-
proteasome inhibitor MG132 suppressing the ubiquitination of
Cx43 ameliorated
lipopolysaccharide-induced
neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in
CUS-exposed rats; and the main mechanism of the
antidepressant-like effects of Rg1 appears to involve protection against
neuroinflammation via suppression of
Cx43 ubiquitination. In conclusion, Rg1 could ameliorate
neuroinflammation via suppression of
Cx43 ubiquitination to attenuate depression, which represents the perspective of an
innovative therapy of Rg1 in the treatment of
inflammation-associated depression.