A diarylheptanoid from lesser galangal (Alpinia officinarum) inhibits proinflammatory mediators via inhibition of mitogen-activated protein kinase, p44/42, and transcription factor nuclear factor-kappa B.
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The diarylheptanoid 7-(4'-hydroxy-3'-methoxyphenyl)-1-phenylhept-4-en-3-one (HMP) is a naturally occurring phytochemical found in lesser galangal (Alpinia officinarum). In the present study, we have demonstrated the anti-inflammatory properties of this compound on mouse macrophage cell line (RAW 264.7) and human peripheral blood mononuclear cells (PBMCs) in vitro. Treatment of RAW 264.7 cells with HMP (6.25-25 microM) significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production. This compound also inhibited the release of LPS-induced proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) from human PB-MCs in vitro. In addition, Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that HMP decreased LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and mRNA expression in RAW 264.7 cells. Furthermore, HMP treatment also reduced nuclear factor-kappa B (NF-kappa B) DNA binding induced by LPS in RAW 264.7 cells. To elucidate the molecular mechanism for inhibition of proinflammatory mediators by HMP (25 microM), we have studied the effect of HMP on LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK). We observed that the phosphorylation of p44/42 MAPK in LPS-stimulated RAW 264.7 cells was markedly inhibited by HMP, whereas activation of p38 MAPK was not affected. These results suggested that HMP from lesser galangal suppressed the LPS-induced production of NO, IL-1 beta, and TNF-alpha and expression of iNOS and COX-2 gene expression by inhibiting NF-kappa B activation and phosphorylation of p44/42 MAPK. (+info)
3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic lipase.
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The pancreatic lipase inhibitory activity of the rhizome of Alpinia officinarum (AO) and its antihyperlipidemic activity were measured. When the water extract of AO was fractionated stepwise with organic solvents, the ethyl acetate fraction exhibited the most potent inhibition. 3-Methylethergalangin was isolated from that fraction as an inhibitor of pancreatic lipase with an IC(50) value of 1.3 mg/ml (triolein as a substrate). AO and its ethyl acetate fraction significantly inhibited the serum TG level in corn oil feeding-induced triglyceridemic mice, and serum triglyceride (TG) and cholesterol in Triton WR-1339-induced hyperlipidemic mice. However, this compound and the AO ethyl acetate fraction did not show hypolipidemic activity in high cholesterol diet-induced hyperlipidemic mice. The results suggest that the hypolipidemic activity of AO and 3-methylethergalangin is due to the inhibition of pancreatic lipase. (+info)
5-Hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone: a pancreatic lipase inhibitor isolated from Alpinia officinarum.
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A pancreatic lipase inhibitor, 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone (HPH), from the rhizome of Alpinia officinarum (AO) was isolated and its antihyperlipidemic activity was measured. HPH inhibited a pancreatic lipase with an IC(50) value of 1.5 mg/ml (triolein as a substrate). HPH significantly lowered the serum TG level in corn oil feeding-induced triglyceridemic mice, and reduced serum triglyceride (TG) and cholesterol in Triton WR-1339-induced hyperlipidemic mice. However, HPH did not show hypolipidemic activity in high cholesterol diet-induced hyperlipidemic mice. Based on these findings, we propose that PL inhibitors may be effective as hypolipidemic agents. (+info)
Inhibitors of nitric oxide production from the rhizomes of Alpinia galanga: structures of new 8-9' linked neolignans and sesquineolignan.
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The 80% aqueous acetone extract from the rhizomes of Alpinia galanga showed nitric oxide (NO) production inhibitory activities in mouse peritoneal macrophages. From the aqueous acetone extract, three new 8-9' linked neolignans, galanganal, galanganols A and B, and a sesquineolignan, galanganol C, were isolated together with nine known phenylpropanoids and p-hydroxybenzaldehyde. The structures of new neolignans were determined on the basis of physicochemical and chemical evidence. In addition, the inhibitory effects of the constituents from the rhizomes of A. galanga on NO production induced by lipopolysaccharide in mouse peritoneal macrophages were examined. Among them, galanganal (IC50=68 microM), galanganols B (88 microM) and C (33 microM), 1'S-1'-acetoxychavicol acetate (2.3 microM), 1'S-1'-acetoxyeugenol acetate (11 microM), trans-p-hydroxycinnamaldehyde (ca. 20 microM), trans-p-coumaryl alcohol (72 microM), and trans-p-coumaryl diacetate (19 microM) were found to show inhibitory activity. (+info)
Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera.
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Nuclear factor-kappaB (NF-kappaB) and the signaling pathways that regulate its activity have become a focal point for intense drug discovery and development efforts. NF-kappaB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and antiapoptotic responses. In our search for NF-kappaB inhibitors from natural resources, we identified cardamomin, 2',4'-dihydroxy-6'-methoxychalcone, as an inhibitor of NF-kappaB activation from Alpinia conchigera Griff (Zingiberaceae). In present study, we demonstrated the effect of cardamomin on NF-kappaB activation in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and LPS-induced mortality. This compound significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha and NO as well as expression of inducible nitric-oxide synthase and cyclooxygenase-2 was significantly suppressed by the treatment of cardamomin in RAW264.7 cells. Also, cardamomin inhibited not only LPS-induced degradation and phosphorylation of inhibitor kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB kinases, but it significantly suppressed LPS-induced activation of Akt. Moreover, cardamomin suppressed transcriptional activity and phosphorylation of Ser536 of RelA/p65 subunit of NF-kappaB. However, this compound did not inhibit LPS-induced activation of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase, but significantly impaired activation of p38 mitogen-activated protein kinase. We also demonstrated that pretreatment of cardamomin rescued C57BL/6 mice from LPS-induced mortality in conjunction with decreased serum level of TNF-alpha. Together, cardamomin could be valuable candidate for the intervention of NF-kappaB-dependent pathological condition such as inflammation. (+info)
New diarylheptanoids from Alpinia pinnanensis.
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Three new diarylheptanoids, called alpinnanins A-C (1-3), together with two known chalcones, 2',4'-dihydroxy-6'-methoxychalcone and 4',6'-dimethylchalconaringenin, two known flavanones, alpinetin and naringenin 5-O-methyl ether, a known diarylheptanoid, (3S,5S)-trans-3,5-dihydroxy-1,7-diphenyl-1-heptene, stigmasterol and beta-sitosterol as a mixture, and beta-sitosterol 3-O-beta-D-glucopyranoside were isolated from the rhizomes of Alpinia pinnanensis T. L. WU et SENJEN (Zingiberaceae). Their structures were elucidated by spectroscopic analyses. (+info)
Suppression of inducible nitric oxide synthase expression by yakuchinones and their analogues.
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Analogues of yakuchinones were synthesized as inhibitors of nitric oxide production in lipopolysaccharide-activated macrophage cell line, RAW 264.7 cells. We prepared stronger inhibitors than the original natural molecules, yakuchinones A and B reported from Alpinia oxyphylla. From the limited structural activity relation study of analogues, we concluded that the optimal length of linker between two aryl groups and the presence of enone moiety in the linker were identified as essential for the activity. The IC50 value of the most potent structure was 0.92 microM. The active analogues suppressed the expression of inducible nitric oxide synthase protein and mRNA. (+info)
1'S-1'-acetoxychavicol acetate isolated from Alpinia galanga inhibits human immunodeficiency virus type 1 replication by blocking Rev transport.
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AIDS remains a major global health concern. Despite a number of therapeutic advancements, there is still an urgent need to develop a new class of therapy for human immunodeficiency virus (HIV). Here, it was shown that 1'S-1'-acetoxychavicol acetate (ACA), a small molecular compound isolated from the rhizomes of Alpinia galanga, inhibited Rev transport at a low concentration by binding to chromosomal region maintenance 1 and accumulating full-length HIV-1 RNA in the nucleus, resulting in a block in HIV-1 replication in peripheral blood mononuclear cells. Additionally, ACA and didanosine acted synergistically to inhibit HIV-1 replication. Thus, ACA may represent a novel treatment for HIV-1 infection, especially in combination with other anti-HIV drugs. (+info)