The Ganoderma lucidum (G. lucidum) is one of the oriental fungi that has been reported to have immunomodulatory properties. Although effect of beta-glucans from G. lucidum has been well documented, little is known about how other major bioactive components, the triterpenes, contribute to the immunomodulatory function of G. lucidum. Here, we showed that triterpenes-rich extract of antlered form of G. lucidum (G. lucidum AF) induces TNF alpha production in monocytic THP-1 cells. Furthermore, the extract also synergized with lipopolysaccharide (LPS) to induce TNF alpha production in THP-1 cells, suggesting an immunostimulatory role of triterpenes-rich extract of G. lucidum AF. Notably, the extract enhanced LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), while it suppressed LPS-induced phosphorylation of c-Jun N-terminal kinase (INK) MAPK. p38 Inhibitor suppressed TNF alpha production, while JNK inhibitor enhanced TNF alpha production, implying that synergistic effect of the extract may work by modulating p38 and JNK MAPKs. Moreover, we found that the triterpenes-rich extract of G. lucidum AF contains high amounts of lucidenic acids. Lucidenic acid-A, -F and -D-2, which seem to dominantly exist in the extract, were purified from the triterpenes-rich extract. We also identified Lucidenic acid-A and -F as modulators of JNK and p38, respectively. Thus, our data demonstrate that lucidenic acids-rich extract from G. lucidum AF enhances LPS-induced immune responses in monocytic THP-1 cells possibly via the modulation of p38 and JNK MAPKs activation. (C) 2011 Elsevier Inc. All rights reserved.