Bupleurum chinense DC. ameliorates depression through hepatic lipopolysaccharide-binding protein-associated...

Bupleurum chinense DC. (Radix Bupleuri, Chaihu) has traditionally been applied to "soothe the liver and relieve depression." Contemporary pharmacological evidence indicates that Radix Bupleuri (RB) and its active components exhibit anti-inflammatory, antitumor, and antidepressant effects. Nevertheless, the mechanisms underlying its antidepressant activity remain unclear.

To evaluate the antidepressant-like effects of RB in mouse models and to determine whether modulation of peripheral inflammatory status is associated with changes in the brain monoamine neurotransmitter system.

A metabolic inflammation mouse model was established to investigate the regulatory effects of RB on hepatic lipopolysaccharide-binding protein (LBP) expression and the transcription of genes involved in the nuclear factor κB (NF-κB) signaling pathway. Subsequently, an inflammatory model was established in human hepatocellular carcinoma cells (HepG2) to examine the effects of saikosaponin and other herbal monomers on LBP expression at the transcriptional level. Finally, the chronic unpredictable mild stress (CUMS) mouse model was used to assess whether RB improves depressive-like behaviors by regulating hepatic LBP and modulating the NF-κB signaling pathway, thereby preserving the catalytic activity of monoamine-synthesizing enzymes, including tyrosine hydroxylase, tryptophan hydroxylase 2, DOPA decarboxylase, and dopamine β-hydroxylase.

RB alleviated lipid metabolic disorders and hepatic inflammatory infiltration in the metabolic inflammation model, downregulated hepatic LBP expression, and suppressed NF-κB pathway activation at the transcriptional level. In vitro, saikosaponin A markedly reduced LBP mRNA expression compared with 15 other herbal monomers. Similarly, RB ameliorated depression-like behaviors in the CUMS model by downregulating hepatic LBP protein and mRNA expression, suppressing NF-κB pathway activation, and mitigating peripheral inflammatory signaling that interferes with the central nervous system. These effects subsequently enhanced monoamine biosynthesis, leading to elevated levels of 5-hydroxytryptamine, norepinephrine, and dopamine.

RB alleviates depression by regulating hepatic LBP through the liver-brain axis to restore brain monoamine balance, consistent with the traditional Chinese medicine concept of "soothing the liver and relieving depression."