The analgesic and anti-inflammatory effects of Litsea japonica fruit are mediated via suppression of NF-κB and JNK/p38 MAPK activation

• L. japonica fruit has anti-nociceptive effects in in vivo pain models.
• The CH2Cl2 fraction of L. japonica fruit had optimal anti-inflammatory effects.
• The CH2Cl2 fraction regulated NF-κB and JNK/p38 MAPK in LPS-induced macrophages.
• L. japonica fruit may be a candidate for anti-inflammatory and analgesic agents.

Fruits of the Litsea family of trees and shrubs contain biologically active compounds, some of which have been used as natural nutrients and flavoring agents in food. In this study, we identified novel anti-nociceptive effects of the 30% ethanol extract, the CH2Cl2 fraction and the associated active components (Hamabiwalactone A and B) from Litsea japonica fruit by using in vivo peripheral and central nervous pain models. In addition, we compared the anti-inflammatory effects of several fractions from L. japonica fruit extracts using lipopolysaccharide (LPS)-stimulated Raw264.7 cells. The CH2Cl2 fraction of L. japonica fruit (LJM) had an optimal combination of anti-inflammatory effects and low cytotoxicity. Dose response studies were performed to determine the inhibitory effects of LJM on the pro-inflammatory enzymes, COX-2/PGE2 and NO/iNOS, and pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α. Molecular profiling revealed that LJM exerts anti-inflammatory effects through inhibition of NF-κB and JNK/p38 MAPK signaling in LPS-induced macrophages. This study suggests that CH2Cl2 fraction of L. japonica fruit and its bioactive components are potential candidates as anti-inflammatory and analgesic agents (painkillers) for the treatment of inflammatory diseases.