The inhibition of JNK MAPK and NF-κB signaling by tenuifoliside A isolated from Polygala tenuifolia in lipopolysaccharide-induced macrophages is associated with its anti-inflammatory effect.
The root of Polygala tenuifolia Willd. (Polygalaceae) is well known for its use in the treatment of neurasthenia, amnesia, and inflammation. In this study, we isolated phenyl propanoid type metabolite tenuifoliside A, one of the phenylpropanoids from P. tenuifolia, and investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. The results showed that tenuifoliside A inhibited the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PG E2), and cyclooxygenase (COX)-2. In addition, tenuifoliside A suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. We also evaluated the effects of tenuifoliside A on the activation of nuclear factor-kappaB (NF-κB). Tenuifoliside A inhibited the translocation of the NF-κB subunit p65 into the nucleus by interrupting the phosphorylation and degradation of inhibitor kappa B (IκB)-α in LPS-stimulated murine peritoneal macrophages. Moreover, we confirmed that the suppression of the inflammatory process by tenuifoliside A was mediated through the mitogen-activated protein kinases (MAPKs) pathway based on the fact that tenuifoliside A significantly decreased p-c-Jun N-terminal kinase (p-JNK) protein expression in LPS-stimulated murine peritoneal macrophages. Taken together, the anti-inflammatory effects of tenuifoliside A were mediated by the inhibition of the NF-κB and MAPK pathways. This study is the first report on the anti-inflammatory effects of tenuifoliside A, and the strong anti-inflammatory effects of tenuifoliside A provide potential compound to be developed as therapeutic for inflammatory diseases.
Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University, Iksan, Republic of Korea; College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
Kyoung-Su
KS
Kim
Dong-Sung
DS
Lee
Gi-Sang
GS
Bae
Sung-Joo
SJ
Park
Dae-Gil
DG
Kang
Ho-Sub
HS
Lee
Hyuncheol
H
Oh
Youn-Chul
YC
Kim
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004186:Disaccharidases / Q000302:isolation & purification / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D031801:Polygala / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D004247:DNA; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D004186:Disaccharidases; C000589515:tenuifoliside A
Inflammation; MAPK pathway; Macrophage; NF-κB pathway; Polygala tenuifolia; Tenuifoliside A