RESUMEN
Hydrangea serrata (THUNB.) SER. (Hydrangeaceae) leaves have been used as herbal teas in Korea and Japan. The objective of this study was to identify anti-photoaging compounds in aqueous EtOH extract prepared from leaves of H. serrata and their effects on UVB-irradiated Hs68 human foreskin fibroblasts. Phytochemical study on H. serrata leaves led to the isolation and characterization of ten compounds: hydrangenol, thunberginol A, thunberginol C, hydrangenoside A, hydrangenoside C, cudrabibenzyl A, 2,3,4'-trihydroxystilbene, thunberginol F, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-galactopyranoside, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-glucopyranoside. Cudrabibenzyl A, 2,3,4'-trihydroxystilbene, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-galactopyranoside, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-glucopyranoside were firstly isolated from H. serrata. We estimated the effects of 10 compounds on cell viability and production of pro-collagen Type I, matrix metalloproteinase (MMP)-1, and hyaluronic acid (HA) after UVB irradiation. Of these compounds, hydrangenol showed potent preventive activities against reduced cell viability and degradation of pro-collagen Type I in UVB-irradiated Hs68 fibroblasts. Hydrangenol had outstanding inductive activities on HA production. It suppressed mRNA expression levels of MMP-1, MMP-3, hyaluronidase (HYAL)-1, HYAL-2, cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-8, and IL-1ß in UVB-irradiated Hs68 fibroblasts. When Hs68 fibroblasts were exposed to hydrangenol after UVB irradiation, UVB-induced reactive oxygen species (ROS) production was suppressed. Hydrangenol also inhibited the activation of activator protein-1 (AP-1) and signal transduction and activation of transcription 1 (STAT-1) by downregulating phosphorylation of p38 and extracellular signal-regulated kinase (ERK). Our data indicate that hydrangenol isolated from H. serrata leaves has potential protective effects on UVB-induced skin photoaging.
Asunto(s)
Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Rayos Ultravioleta/efectos adversos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Humanos , Hydrangea , Extractos Vegetales/química , Envejecimiento de la PielRESUMEN
An activity-guided fractionation procedure of the 70% aqueous EtOH extract from the roots of Patrinia scabra led to the isolation and characterization of five new iridoids, patriscabrins A-E (1-5), along with 13 known compounds. The structures of 1-5 were determined by interpretation of spectroscopic data, particularly by 1D and 2D NMR, ECD, and VCD studies. Thereafter, isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. Of these, the new iridoids 2 and 5 and the known lignan patrineolignan B (6) exhibited IC50 values of 14.7 to 17.8 µM.
Asunto(s)
Iridoides/química , Iridoides/farmacología , Lipopolisacáridos/farmacología , Óxido Nítrico/metabolismo , Patrinia/química , Raíces de Plantas/química , Animales , Línea Celular , Lignanos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Ratones , Células RAW 264.7RESUMEN
PURPOSE: The purpose of this study was to compare the clinical outcomes of immediate rotator cuff repair with capsular release and those of rotator cuff repair after the stiffness was treated with rehabilitative therapy. METHODS: Between June 2007 and December 2010, we recruited 63 patients with rotator cuff tears and stiffness. In 33 patients arthroscopic rotator cuff repair was performed with capsular release simultaneously (group I). In 30 patients arthroscopic rotator cuff repair was performed after 6 months of preoperative rehabilitation for stiffness (group II). The American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, Constant score, and visual analog scale score for pain and range of motion (ROM) were assessed at the start of the study; at 3, 6, and 12 months; and at the last visit. The postoperative cuff tendon integrity was assessed between 6 and 12 months using magnetic resonance or ultrasound images. RESULTS: There were no significant differences in preoperative demographic data between the groups (P > .05). The mean follow-up period was 21.54 months. After treatment, there was significant improvement in ROM and functional scores in both groups, as measured at the last follow-up (P < .05). No statistical differences were found in clinical scores and ROM at the last follow-up (P > .05). On assessment of the magnetic resonance or ultrasound images taken 6 to 12 months postoperatively, the retear rate for the repaired cuff tendon in each group was 12.1% in group I and 13.4% in group II. CONCLUSIONS: In the treatment of rotator cuff tears with stiffness, satisfactory results can be achieved either by repairing the tear with simultaneous capsular release or by waiting to perform the repair after preoperative rehabilitation for stiffness. Because a delayed rotator cuff repair after improving ROM offered no clear advantage over an immediate operation, we recommend surgically treating rotator cuff tears with concomitant stiffness early using a simultaneous capsular release method to save time and to avoid unnecessary rehabilitation. LEVEL OF EVIDENCE: Level II, prospective comparative study.
Asunto(s)
Manguito de los Rotadores/cirugía , Articulación del Hombro/cirugía , Traumatismos de los Tendones/cirugía , Anciano , Artroscopía , Femenino , Humanos , Liberación de la Cápsula Articular , Artropatías/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rango del Movimiento Articular , Manguito de los Rotadores/fisiopatología , Lesiones del Manguito de los Rotadores , Traumatismos de los Tendones/rehabilitación , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cirsium japonicum var. ussuriense (Regel) Kitam. ex Ohwi (C. ussuriense) is known as "Dae-Gye" or "Korean milk thistle". C. ussuriense have long been used as a folk medicinal plant for inflammatory diseases such as hepatitis, nephritis, and mastitis in Korea, China, and Japan. To reveal the anti-inflammatory components of C. ussuriense, we isolated three flavone glycosides (linarin, cirsimarin, and hispidulin-7-O-neohesperidoside) from the aerial part of C. ussuriense and evaluated their inhibitory effects on LPS-induced pro-inflammatory mediators in macrophages. We also investigated the involving molecular mechanisms of cirsimarin. Among three flavone glycosides, cirsimarin showed vastly superior inhibitory potency in LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. Cirsimarin concentration-dependently inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in macrophages. Cirsimarin suppressed the production and mRNA expression of tumor necrosis factor- α (TNF-α) and interleukin (IL)-6 in LPS-stimulated RAW 264.7 and bone marrow-derived macrophages. Moreover, molecular data presented that cirsimarin down-regulated the phosphorylation of Janus kinase (JAK)/signal transducer and activator of transcriptions (STATs) and p38 mitogen-activated protein kinase (MAPK), and nuclear translocation of interferon regulatory factor (IRF)-3. Collectively, cirsimarin may be an active ingredient responsible for anti-inflammatory effects of C. ussuriense and it may act as a promising therapeutic against inflammatory diseases by suppressing the JAK/STAT and IRF-3 signaling pathway.
Asunto(s)
Cirsium/química , Flavonas/farmacología , Glicósidos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Cirsium/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Flavonas/química , Flavonas/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Factor 3 Regulador del Interferón/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Quinasas Janus/metabolismo , Lipopolisacáridos/toxicidad , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Células RAW 264.7 , Factores de Transcripción STAT/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The combination of magnetic and plasmonic properties using iron oxide/gold nanocomposite particles is crucial for the development of multimodal molecular imaging probes. In this study, iron oxide/gold composite nanoparticles (NanoIOGs) were synthesized via the on-site reduction of an Au precursor salt by polyethyleneimine (PEI) molecules attached to iron oxide nanoparticles (IONPs), and they were employed in magnetic resonance and dark-field microscope imaging. PEI is considered as a polymeric active stabilizer (PAS), acting as a reducing agent for the synthesis of Au and a dispersant for nanoparticles. When the IONPs prepared at the PEI concentration of 0.02 wt. % were used for the NanoIOG synthesis, Au nanoseeds were formed around the IONPs. The alloy clusters of IONPs/Au crystals were produced with further reduction depending on PEI concentration. The NanoIOGs exhibited superparamagnetism in a magnetic field and plasmonic response in a dark-field (DF) microscope. The sizes, morphologies, magnetizations, and r2 relaxivities of NanoIOGs were affected significantly by the amount of PEI added during the NanoIOG synthesis. It is suggested that the PAS-mediated synthesis is simple and effective, and can be applied to various nanostructured Au-metal alloys.
RESUMEN
Kaempferol 7-O-ß-D-glucoside (KPG), a natural flavonol isolated from Cudrania tricuspidata, has been reported to exert anti-cancer effects; however, its anti-inflammatory effects have not yet been reported. In this study, we demonstrate the suppressive effect of KPG on the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and mouse bone marrow-derived macrophages. KPG downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level and iNOS, COX-2, TNF-α, IL-1ß, and IL-6 at the mRNA level in LPS-treated RAW 264.7 macrophages. Moreover, we elucidated the underlying molecular mechanism, demonstrating that KPG attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 nuclear translocation, inhibiting κBα (IκBα) phosphorylation/degradation and IκB kinaseα/ß (IKKα/ß) phosphorylation. KPG additionally reduced LPS-induced activator protein-1 (AP-1) activity by inhibiting c-Fos expression in the nucleus, though c-Jun was not affected. Furthermore, we revealed that KPG significantly abrogated the LPS-induced phosphorylation of signal transducer and activator of transcription (STAT) 1 (Ser 727, Tyr 701) and STAT3 (Tyr 705) through inhibiting the phosphorylation of Janus kinase (JAK) 1 and JAK2, its upstream activating proteins. Taken together, our data suggest that KPG induces anti-inflammatory activity by blocking NF-κB, AP-1, and JAK-STAT signaling pathways in LPS-treated RAW 264.7 macrophages, thus suppressing inflammatory mediators.
Asunto(s)
Mediadores de Inflamación/metabolismo , Quempferoles/farmacología , Lipopolisacáridos/toxicidad , Moraceae/química , Transducción de Señal/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Quinasas Janus/metabolismo , Quempferoles/química , Quempferoles/aislamiento & purificación , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Moraceae/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Células RAW 264.7 , Factores de Transcripción STAT/metabolismo , Factor de Transcripción AP-1/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Although xanthotoxin has been reported to possess skin-protective and anti-oxidative properties, its anti-inflammatory capacity has not been studied to date. Therefore, we investigated this role as well as the molecular mechanisms of xanthotoxin in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Xanthotoxin inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) by the LPS-induced macrophages in a concentration-dependent manner. It also suppressed the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at the protein levels and iNOS, COX-2, TNF-α, and IL-6 at the mRNA levels. At a molecular level, the effects were related to xanthotoxin-mediated attenuation of the LPS-induced transcriptional and DNA-binding activity of activator protein-1 (AP-1). This attenuation was associated with decreased phosphorylation of c-Fos, but not c-Jun. Xanthotoxin also displayed a suppressive effect on the transcriptional and DNA-binding activity of nuclear transcription factor kappa-B (NF-κB) by inhibiting p65 nuclear translocation. In addition, xanthotoxin significantly reduced the phosphorylation at signal transducers and activators of transcription 1 (STAT1, Ser 727 and Tyr 701) and STAT3 (Tyr 705), as well as Janus kinase (JAK) 1 and 2 in LPS-induced RAW 264.7 macrophages. Finally, xanthotoxin suppressed the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). Taken together, these results indicate that xanthotoxin decreases NO, PGE2, TNF-α, and IL-6 production by downregulation of the NF-κB, AP-1, and JAK/STAT signaling pathways in LPS-induced RAW 264.7 macrophages.