Panax vietnamensis Ha et Grushv., with its main constituents
vina-ginsenoside R2 (VR2) and
majonoside R2 (MR2), is used in traditional
folk medicine in the hill tribes of Vietnam for anti-
fatigue, anti-inflammatory, and life-saving purposes. In a preliminary study, VR2 and MR2 were shown to be metabolized to
pseudoginsenoside RT4 (PRT4) and
ocotillol by human gut microbiota. Therefore, we measured the anti-inflammatory effects of VR2, MR2, and their metabolites in
lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. Among these
ginsenosides, only VR2 exhibited cytotoxicity against peritoneal macrophages. MR2, PRT4, and
ocotillol inhibited LPS-stimulated
transcription factor (NF)-κB activation, and expression of the proinflammatory
cytokines tumor necrosis factor-α and
interleukin (IL)-1. However, these
ginsenosides did not inhibit
peptidoglycan-induced NF-κB activation in the macrophages. These three
ginsenosides also inhibited LPS-stimulated
cyclooxygenase-2 and inducible
NO synthase expression, and phosphorylation of NF-κB signal molecules
IL-1 receptor-associated kinase 1 and
tumor growth factor-β-activated
kinase 1 in peritoneal macrophages. Treatment with either PRT4 or
ocotillol inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages, as observed by flow cytometry. They also potently inhibited the binding of LPS to TLR4 on peritoneal macrophages, both with and without transfected MyD88
siRNA. Among the tested
ginsenosides,
ocotillol exhibited the strongest inhibitory effect on
inflammation in LPS-stimulated macrophages via the NF-κB signaling pathway. Based on these findings, orally administered VR2 and MR2 of P. vietnamensis may be metabolized to
ocotillol via PRT4, and the metabolites, particularly
ocotillol, may inhibit
inflammation by inhibiting the binding of LPS to TLR4 on macrophages.