RESUMEN
In this study, a series of rosmarinic acid and analogs were investigated for their anti-inflammatory potential against LPS-induced alveolar macrophages (MH-S). Our results showed that, among the test compounds, ethyl rosmarinate (3) exhibited the most potent inhibitory effect on NO production in LPS-induced MH-S cells, with low cytotoxicity. Compound 3 exhibited remarkable inhibition of the production of PGE2 in LPS-induced MH-S cells. The inhibitory potency of compound 3 against LPS-induced NO and PGE2 release was approximately two-fold higher than that of dexamethasone. Compound 3 significantly decreased the mRNA and protein expression of iNOS and COX-2 and suppressed p65 expression in the nucleus in LPS-induced MH-S cells. These results suggested that compound 3 inhibited NO and PGE2 production, at least in part, through the down-regulation of NF-κB activation. Analysis of structure-activity relationship revealed that the free carboxylic group did not contribute to inhibitory activity and that the alkyl group of the corresponding alkyl ester analogs produced a strong inhibitory effect. We concluded that compound 3, a structurally modified rosmarinic acid, possessed potent inhibitory activity against lung inflammation, which strongly supported the development of this compound as a novel therapeutic agent for the treatment of macrophage-mediated lung inflammatory diseases, such as COPD.
Asunto(s)
Cinamatos/farmacología , Depsidos/farmacología , Dinoprostona/biosíntesis , Lipopolisacáridos/farmacología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Óxido Nítrico/biosíntesis , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Macrófagos Alveolares/citología , Ratones , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ácido RosmarínicoRESUMEN
The ethyl acetate extract of leaves of Murraya paniculata (L.) Jack was described in the previous in vitro study on the inhibition effect on the growth of periodontopathic bacteria and the reduction of cytokines from LPS-stimulated macrophages. In this study, four coumarins including murrangatin (1), murrangatin acetate (2), murranganonesenecionate (3), micropubescin (4) and one flavonoid, 3', 4', 5', 7-tetramethoxyflavone (5) were isolated from the leaves of ethyl acetate extract of M. paniculata. MTT assay was used to test cytotoxicity on human gingival fibroblast and monocytes. The isolated compounds were evaluated for their antibacterial effect against Porphyromonas gingivalis (ATCC33277) and anti-inflammation on lipopolysaccharide-stimulated inflammation using monocyte cells. All isolated compounds exhibited antibacterial activity against P. gingivalis (ATCC 33277). Murranganonesenecionate (3) was highly potent anti-inflammation properties. The coumarin constituents from M. paniculata leaves might be potential lead molecules for the development of antimicrobial drugs for treating periodontal disease.
Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios/farmacología , Cumarinas/farmacología , Flavonoides/farmacología , Inflamación/prevención & control , Extractos Vegetales/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Rutaceae , Antibacterianos/aislamiento & purificación , Antibacterianos/toxicidad , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/toxicidad , Supervivencia Celular/efectos de los fármacos , Cumarinas/aislamiento & purificación , Cumarinas/toxicidad , Relación Dosis-Respuesta a Droga , Fibroblastos/efectos de los fármacos , Fibroblastos/inmunología , Fibroblastos/metabolismo , Flavonoides/aislamiento & purificación , Flavonoides/toxicidad , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Concentración 50 Inhibidora , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Hojas de la Planta , Plantas Medicinales , Porphyromonas gingivalis/crecimiento & desarrollo , Rutaceae/química , Células U937RESUMEN
Nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, frequently causes biofilm infections. Currently, resistance of bacteria within the biofilm to conventional antimicrobials poses a major obstacle to effective medical treatment on a global scale. Novel agents that are effective against NTHi biofilm are therefore urgently required. In this study, a series of natural and synthetic chalcones with various chemical substituents were evaluated in vitro for their antibiofilm activities against strong biofilm-forming strains of NTHi. Of the test chalcones, 3-hydroxychalcone (chalcone 8) exhibited the most potent inhibitory activity, its mean minimum biofilm inhibitory concentration (MBIC50 ) being 16 µg/mL (71.35 µM), or approximately sixfold more active than the reference drug, azithromycin (MBIC50 419.68 µM). The inhibitory activity of chalcone 8, which is a chemically modified chalcone, appeared to be superior to those of the natural chalcones tested. Significantly, chalcone 8 inhibited biofilm formation by all studied NTHi strains, indicating that the antibiofilm activities of this compound occur across multiple strong-biofilm forming NTHi isolates of different clinical origins. According to antimicrobial and growth curve assays, chalcone 8 at concentrations that decreased biofilm formation did not affect growth of NTHi, suggesting the biofilm inhibitory effect of chalcone 8 is non-antimicrobial. In terms of structure-activity relationship, the possible substituent on the chalcone backbone required for antibiofilm activity is discussed. These findings indicate that 3-hydroxychalcone (chalcone 8) has powerful antibiofilm activity and suggest the potential application of chalcone 8 as a new therapeutic agent for control of NTHi biofilm-associated infections.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Chalcona/farmacología , Haemophilus influenzae/efectos de los fármacos , Chalcona/química , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/aislamiento & purificación , Haemophilus influenzae/fisiología , HumanosRESUMEN
Root exudates from the allelopathic plant, black oat (Avena strigosa Schreb.), were found to contain at least six different germination stimulants for root parasitic plants, but no known strigolactones (SLs). One of these germination stimulants was purified and named avenaol. Its HR-ESI-TOFMS analysis indicated that the molecular formula of avenaol is C20H24O7, and thus it contains an additional carbon compared with known C19-SLs. Its structure was determined as 5-((E)-(5-(3-hydroxy-1,5,5-trimethyl-2-oxobicyclo[4.1.0]heptan-7-yl)-2-oxodihydrofuran-3(2H)-ylidene)methoxy)-3-methylfuran-2(5H)-one, by 1D and 2D NMR spectroscopy, and ESI- and EI-MS spectrometry. Although avenaol contains the C-D moiety, the common structural feature for all known SLs, it lacks the B ring and has an additional carbon atom between the A and C rings. Avenaol is a potent germination stimulant of Phelipanche ramosa seeds, but only a weak stimulant for seeds of Striga hermonthica and Orobanche minor.
Asunto(s)
Germinación/efectos de los fármacos , Lactonas/química , Lactonas/farmacología , Exudados de Plantas/química , Raíces de Plantas/química , Poaceae/química , Orobanche/efectos de los fármacos , Exudados de Plantas/farmacología , Striga/efectos de los fármacosRESUMEN
Three new diarylheptanoids, a 1:2 mixture of (3S)- and (3R)-1-(4-methoxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (13a and 13b) and 1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-one (15), together with two synthetically known diarylheptanoids 1,7-diphenyl-(1E,3E,5E)-1,3,5-triene (9) and 1-(4-hydroxyphenyl)-7-phenyl-(4E,6E)-4,6-heptadien-3-one (16), and nine known diarylheptanoids, 2, 8, 10-12, 14, a 3:1 mixture of 17a and 17b, and 18, were isolated from the rhizomes of Curcuma comosa Roxb. The absolute stereochemistry of the isolated compounds has also been determined using the modified Mosher's method. The isolated compounds and the chemically modified analogues were evaluated for their estrogenic-like transcriptional activity using RT-PCR in HeLa cell line. Some of the isolated diarylheptanoids and their modified analogues exhibited estrogenic activity comparable to or higher than that of the phytoestrogen genistein. Based on the transcriptional activation of both estrogenic targets, Bcl-xL and ERbeta gene expression, the structural features for a diarylheptanoid to exhibit high estrogenic activity are the presence of an olefinic function conjugated with the aromatic ring at the 7-position, a keto group at the 3-position, and a phenolic hydroxyl group at the p-position of the aromatic ring attached to the 1-position of the heptyl chain.