8-Prenylkaempferol
8-Prenylkaempferol is an effective agent for attenuating pro-inflammatory NO induction, it may be an anti-inflammatory agent for suppressing influenza A virus-induced RANTES production acts by blocking PI3K-mediated transcriptional activation of NF-κB and IRF-3 and in part by interfering with IκB degradation which subsequently decreases NF-κB translocation. 8-Prenylkaempferol induces differentiation/maturation of MC3T3-E1 osteoblasts by BMP-2/p38/Runx2 pathways , might be a promising agent for inducing osteogenesis.
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Life Sci. 2011 Feb 14;88(7-8):335-42.
8-Prenylkaempferol accelerates osteoblast maturation through bone morphogenetic protein-2/p38 pathway to activate Runx2 transcription.[Pubmed:
21163272]
In this study, we investigated the effect of 8-Prenylkaempferol (8-PK), a prenyl-flavonoid isolated from Sophora flavescens, on osteoblast differentiation and maturation.
METHODS AND RESULTS:
MC3T3-E1 cells were exposed to 8-Prenylkaempferol and the cytotoxicity was assayed. Osteoblast differentiation and maturation were evaluated by analyzing alkaline phosphatase (ALP) activity and cell mineralization, respectively. RT-PCR and Western blot were executed to determine the effects of 8-Prenylkaempferol on osteoblast differentiation-related gene expression and signaling pathway. 8-Prenylkaempferol significantly promoted ALP activity, up-regulated mRNA expressions of osteocalcin, osteopontin, and type I collagen, and induced bone nodules formation. Induction of differentiation by 8-Prenylkaempferol was associated with increased bone morphogenetic protein (BMP)-2 expression, and sequentially up-regulated the phosphorylations of Smad1/5/8 and p38, and increased the nuclear translocation of runt-related transcription factor 2 (Runx2). Addition of BMP-2 antagonist noggin blocked 8-Prenylkaempferol and recombinant mouse BMP-2-induced ALP activity, reconfirming that BMP-2 production is required in 8-Prenylkaempferol-mediated osteoblast differentiation. Noggin also abrogated 8-Prenylkaempferol evoked phosphorylations of Smad1/5/8 and p38, suggesting that BMP-2 signaling is required for p38 activation in 8-Prenylkaempferol-treated cells. Application of p38 inhibitor SB203580 repressed not only 8-Prenylkaempferol-mediated activation of ALP, but also the nuclear translocation of Runx2 and bone nodules formation.
CONCLUSIONS:
The present results suggested that BMP-2/p38/Runx2 pathways were involved in 8-Prenylkaempferol-induced differentiation/maturation of MC3T3-E1 osteoblasts and firstly demonstrated that 8-Prenylkaempferol might be a promising agent for inducing osteogenesis.
Evid Based Complement Alternat Med. 2011;2011:920828.
8-Prenylkaempferol Suppresses Influenza A Virus-Induced RANTES Production in A549 Cells via Blocking PI3K-Mediated Transcriptional Activation of NF-κB and IRF3.[Pubmed:
19592477]
8-Prenylkaempferol (8-PK) is a prenylflavonoid isolated from Sophora flavescens, a Chinese herb with antiviral and anti-inflammatory properties.8-Prenylkaempferol could significantly inhibit not only RANTES production but also NF-κB and IRF-3 nuclear translocation.
METHODS AND RESULTS:
We had proved that both NF-κB and IRF-3 participated in H1N1-induced RANTES production since NF-κB inhibitor pyrrolidinedithio carbamate (PDTC) and IRF-3 siRNA attenuated significantly RANTES accumulation. H1N1 inoculation also increased PI3K activity as well as Akt phosphorylation and such responsiveness were attenuated by 8-Prenylkaempferol. Furthermore, 8-Prenylkaempferol but not wortmannin, prevented effectively H1N1-evoked IκB degradation.
CONCLUSIONS:
In conclusion, 8-Prenylkaempferol might be an anti-inflammatory agent for suppressing influenza A virus-induced RANTES production acts by blocking PI3K-mediated transcriptional activation of NF-κB and IRF-3 and in part by interfering with IκB degradation which subsequently decreases NF-κB translocation.
Eur J Pharmacol. 2008 Aug 20;590(1-3):430-6.
8-Prenylkaempferol suppresses inducible nitric oxide synthase expression through interfering with JNK-mediated AP-1 pathway in murine macrophages.[Pubmed:
18579129]
8-Prenylkaempferol is a prenylflavonoid isolated from the roots of Sophora flavescens, a Chinese herb with anti-inflammatory properties. However whether 8-Prenylkaempferol itself displayed an anti-inflammatory activity remained unclear.
METHODS AND RESULTS:
In this study, we evaluated the effect of 8-Prenylkaempferol on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. 8-Prenylkaempferol inhibited significantly LPS-induced NO production through suppressing inducible NO synthase (iNOS) expression at both protein and mRNA levels but failed to affect sodium nitroprusside-triggered NO production, iNOS enzyme activity, and cell viability. Further investigation of the mechanisms revealed that 8-Prenylkaempferol inhibited LPS-induced c-Jun phosphorylation (a major component of activator protein-1, AP-1), but did not attenuate IkB-alpha degradation nor NF-kappaB nuclear translocation. Cellular signaling analysis using mitogen-activating protein kinase (MAPK) inhibitors including 2'-amino-3'-methoxyflavone (PD98059, MEK1/2 inhibitor), 4-[5-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl]pyridine (SB203580, p38 kinase inhibitor) and anthra[1-9-cd]pyrazol-6(2H)-one (SP600125, c-Jun N-terminal kinase inhibitor) demonstrated that extracellular signal-regulated kinase1/2 (ERK1/2), p38 and JNK all participated in LPS-stimulated iNOS expression and NO production, but 8-Prenylkaempferol interfered selectively with JNK phosphorylation. On the other hand, LPS-induced c-Jun phosphorylation was attenuated in the presence of SP600125.
CONCLUSIONS:
We suggested that interfering with JNK-mediated c-Jun phosphorylation and thus blocking AP-1 activation might contribute to the suppression effects of 8-Prenylkaempferol on iNOS. These findings provided the first molecular basis that 8-Prenylkaempferol is an effective agent for attenuating pro-inflammatory NO induction.
