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Depression is a common mental disorder in modern society. A traditional Chinese medicine Huanglian-Wendan decoction with potential anti-inflammation is used as a clinical antidepressant. Our previous study showed central and peripheral inflammatory responses in a rat model of depression developed by chronic unpredictable mild stress (CUMS). Here, we investigated the anti-inflammatory activity and mechanism of Huanglian-Wendan decoction in CUMS rats. LC-MS/MS and HPLC were performed to determine the major compounds in water extract of this decoction. This study showed that Huanglian-Wendan decoction significantly increased sucrose consumption and reduced serum levels of interleukin-1 beta (IL-1 β ), IL-6, and alanine aminotransferase (ALT) in CUMS rats. Moreover, this decoction inhibited nuclear entry of nuclear factor-kappa B (NF- κ B) with the reduction of phosphorylated protein of NF- κ B (p-NF- κ B) and inhibitor of NF- κ B alpha (p-I κ B α ) and downregulated protein of nod-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), and IL-1 β  in liver and brain regions of CUMS rats. These findings demonstrated that Huanglian-Wendan decoction had antidepressant activity with hepatoprotection in CUMS rats coinciding with its anti-inflammation in both periphery and central. The inhibitory modulation of NF- κ B and NLRP3 inflammasome activation by Huanglian-Wendan decoction may mediate its antidepressant action.

Huanglian-Wendan Decoction Inhibits NF-κB/NLRP3 Inflammasome Activation in Liver and Brain of Rats Exposed to Chronic Unpredictable Mild Stress