RESUMEN
Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in the pathogenesis of inflammatory diseases, and its pro- and anti-inflammatory effects have been reported for different ALOX-isoforms. Human ALOX15B oxygenates arachidonic acid to its 15-hydroperoxy derivative, whereas the corresponding 8-hydroperoxide is formed by mouse Alox15b (Alox8). This functional difference impacts the biosynthetic capacity of the two enzymes for creating pro- and anti-inflammatory eicosanoids. To explore the functional consequences of the humanization of the reaction specificity of mouse Alox15b in vivo, we tested Alox15b knock-in mice that express the arachidonic acid 15-lipoxygenating Tyr603Asp and His604Val double mutant of Alox15b, instead of the arachidonic acid 8-lipoxygenating wildtype enzyme, in two different animal inflammation models. In the dextran sodium sulfate-induced colitis model, female Alox15b-KI mice lost significantly more bodyweight during the acute phase of inflammation and recovered less rapidly during the resolution phase. Although we observed significant differences in the colonic levels of selected pro- and anti-inflammatory eicosanoids during the time-course of inflammation, there were no differences between the two genotypes at any time-point of the disease. In Freund's complete adjuvant-induced paw edema model, Alox15b-KI mice were less susceptible than outbred wildtype controls, though we did not observe significant differences in pain perception (Hargreaves-test, von Frey-test) when the two genotypes were compared. our data indicate that humanization of the reaction specificity of mouse Alox15b (Alox8) sensitizes mice for dextran sodium sulfate-induced experimental colitis, but partly protects the animals in the complete Freund's adjuvant-induced paw edema model.
Asunto(s)
Colitis , Dextranos , Humanos , Ratones , Femenino , Animales , Ácido Araquidónico , Inflamación/genética , Mamíferos , Antiinflamatorios , Edema/inducido químicamente , Edema/genética , Modelos Animales de EnfermedadRESUMEN
BACKGROUND, OBJECTIVES AND DESIGN: Arachidonic acid 15-lipoxygenase (ALOX15) has been implicated in the pathogenesis of inflammatory diseases but since pro- and anti-inflammatory roles have been suggested, the precise function of this enzyme is still a matter of discussion. To contribute to this discussion, we created transgenic mice, which express human ALOX15 under the control of the activating protein 2 promoter (aP2-ALOX15 mice) and compared the sensitivity of these gain-of-function animals in two independent mouse inflammation models with Alox15-deficient mice (loss-of-function animals) and wildtype control animals. MATERIALS AND METHODS: Transgenic aP2-ALOX15 mice were tested in comparison with Alox15 knockout mice (Alox15-/-) and corresponding wildtype control animals (C57BL/6J) in the complete Freund's adjuvant induced hind-paw edema model and in the dextran sulfate sodium induced colitis (DSS-colitis) model. In the paw edema model, the degree of paw swelling and the sensitivity of the inflamed hind-paw for mechanic (von Frey test) and thermal (Hargreaves test) stimulation were quantified as clinical readout parameters. In the dextran sodium sulfate induced colitis model the loss of body weight, the colon lengths and the disease activity index were determined. RESULTS: In the hind-paw edema model, systemic inactivation of the endogenous Alox15 gene intensified the inflammatory symptoms, whereas overexpression of human ALOX15 reduced the degree of hind-paw inflammation. These data suggest anti-inflammatory roles for endogenous and transgenic ALOX15 in this particular inflammation model. As mechanistic reason for the protective effect downregulation of the pro-inflammatory ALOX5 pathways was suggested. However, in the dextran sodium sulfate colitis model, in which systemic inactivation of the Alox15 gene protected female mice from DSS-induced colitis, transgenic overexpression of human ALOX15 did hardly impact the intensity of the inflammatory symptoms. CONCLUSION: The biological role of ALOX15 in the pathogenesis of inflammation is variable and depends on the kind of the animal inflammation model.
Asunto(s)
Araquidonato 15-Lipooxigenasa , Colitis , Humanos , Ratones , Femenino , Animales , Ratones Transgénicos , Adyuvante de Freund , Araquidonato 15-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/metabolismo , Araquidonato 15-Lipooxigenasa/uso terapéutico , Dextranos/efectos adversos , Dextranos/metabolismo , Ratones Endogámicos C57BL , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Antiinflamatorios/farmacología , Ratones Noqueados , Edema/inducido químicamente , Edema/genética , Edema/metabolismo , Sulfato de Dextran/efectos adversos , Sulfato de Dextran/metabolismo , Modelos Animales de EnfermedadRESUMEN
Traditional Chinese medicine (TCM) has been long time used in China and gains ever-increasing worldwide acceptance. Er Miao San (EMS), a TCM formula, has been extensively used to treat inflammatory diseases, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the underlying mechanisms of EMS in treating human rheumatoid arthritis (RA) and other inflammatory conditions. Quercetin, wogonin and rutaecarpine were probably the main active compounds of EMS in RA treatment as they affected the most RA-related targets, and TNF-α, IL-6 and IL-1ß were considered to be the core target proteins. The main compounds in EMS bound to these core proteins, which was further confirmed by molecular docking and bio-layer interferometry (BLI) analysis. Moreover, the potential molecular mechanisms of EMS predicted from network pharmacology analysis, were validated in vivo and in vitro experiments. EMS was found to inhibit the production of NO, TNF-α and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells; reduce xylene-induced mouse ear edema; and decrease the incidence of carrageenan-induced rat paw edema. The carrageenan-induced up-regulation of TNF-α, IL-6 and IL-1ß mRNA expression in rat paws was down-regulated by EMS, consistent with the network pharmacology results. This study provides evidence that EMS plays a critical role in anti-inflammation via suppressing inflammatory cytokines, indicating that EMS is a candidate herbal drug for further investigation in treating inflammatory and arthritic conditions.
Asunto(s)
Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Fitoquímicos/farmacología , Animales , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Carragenina , Citocinas/genética , Citocinas/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/genética , Edema/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Farmacología en Red , Óxido Nítrico/metabolismo , Fitoquímicos/uso terapéutico , Células RAW 264.7 , Ratas Sprague-Dawley , XilenosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia zeylanica (L.) Less (Family: Compositae) is a medicinal plant used as external applications for boils, bone fractures, eczema and internally for asthma in traditional medicine in Sri Lanka. Anti-nociceptive, anti-bacterial and anti-proliferative activities have been reported previously. AIM OF THE STUDY: To investigate the anti-inflammatory activity of methanol/dichloromethane extract (MDE) of leaves of V. zeylanica by assessing in vivo inhibition of rat paw-edema, in vitro inhibition of the production of nitric oxide (NO) and superoxide and inhibitory effect on inducible nitric oxide synthase (iNOS) gene expression. MATERIALS AND METHODS: In vivo anti-inflammatory activity of MDE was tested at the dose of 1500 mg/kg using rat paw-edema model. Indomethacin and Gum acacia was used as the positive and vehicle control respectively. In vitro NO inhibitory activity of 7.8-250 µg/ml MDE was tested using lipopolysaccharide (LPS)-stimulated (1 µg/ml) mouse macrophages (RAW264.7 cells) and rat peritoneal cells (RPC) obtained following carrageenan-induction (5 mg/Kg). Griess method was used to quantify the nitrite levels in culture supernatants. In vitro inhibition of superoxide production of Phorbal 12-myristate 13-acetate (PMA)-stimulated RAW cells was determined by quantitative Nitroblue Tetrazolium (NBT) assay. N-monomethyl-L-arginine acetate (NMMA) (1 mM) and Diphenyleneiodonium chloride (DPI) (10 µM) were used as the positive controls for inhibitory activity of NO and superoxide production respectively. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was carried out to test the inhibitory effect on mRNA expression of iNOS gene. RESULTS: Treatment with MDE of V. zeylanica at 1500 mg/kg showed significant inhibition of paw-edema from 1st-5th hour (P < 0.01) compared with the control. The reference drug, indomethacin showed a biphasic pattern and its highest inhibition was (98.3 ± 7.1%) at 4th h (P < 0.01). MDE of V. zeylanica showed similar inhibition of paw-edema with highest inhibition recorded as 94.5 ± 5.28%, at 5th h (P < 0.01). The inhibitory concentration (IC50) of MDE for in vitro NO inhibitory activity was 105 µg/ml for RAW cells and 80 µg/ml for RPCs. Both NO inhibitory activities showed significant dose-dependency (r = 0.998 and r = 0.915 respectively; p < 0.05). MDE concentration of 250 µg/ml showed 55% inhibition of ROS production in RAW cells. NMMA showed 78% and 70.1% inhibition of NO production with RAW cells and RPCs whereas DPI showed 61% superoxide inhibitory activity with RAW cells. NO inhibitory activity of MDE on RAW cells was confirmed by the significant reduction (99.1%) in iNOS gene expression. CONCLUSION: These results demonstrated potent anti-inflammatory activity of MDE of V. zeylanica reflected by its significant in vivo inhibition of rat paw-edema, in vitro inhibition of NO and superoxide production, and the reduction of iNOS gene expression. Thus, further purification and isolation of bioactive compounds from V. zeylanica are emphasized.
Asunto(s)
Antiinflamatorios/uso terapéutico , Edema/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Vernonia , Animales , Antiinflamatorios/farmacología , Carragenina , Modelos Animales de Enfermedad , Edema/inducido químicamente , Edema/genética , Edema/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/farmacología , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Cavidad Peritoneal/citología , Extractos Vegetales/farmacología , Hojas de la Planta , Células RAW 264.7 , Ratas Wistar , Superóxidos/metabolismoRESUMEN
BACKGROUND: White tea, considered to be the oldest form of tea, is becoming a popular beverage for its organoleptic characteristics. Peppermint tea, used as a herbal remedy for centuries, is now also very popular throughout the world as herbal tea. What interested us was that in ancient China, peppermint was used in combination with tea as a detoxification or anti-inflammatory agent. However, there are few reports on the combined use of white tea and peppermint. Therefore, this study aims to investigate the antibacterial and anti-inflammatory activities of white tea in combination with peppermint. RESULTS: A synergistic inhibitory effect against four bacterial strains, especially against Staphylococcus argenteus, was observed in the combination of white tea and peppermint in vitro. In addition, the combined formula demonstrated a stronger anti-inflammatory effect in vivo than either of the two used alone, which was associated with the decrease of the pro-inflammatory cytokines of interleukin-6 (IL-6), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In a further mechanism study, it was found that white tea and peppermint inhibited the phosphorylation of p-IκB-α and mitogen-activated protein kinase (MAPK) at different degrees. While the enhanced anti-inflammatory effect of the combined formula was associated with the combination of NF-κB down-regulation and p-MAPK inhibition. CONCLUSION: In our study, it was for the first time shown that when white tea was combined with peppermint, the antibacterial and anti-inflammatory effects were enhanced. The results suggested an effective application of white tea in combination with peppermint as a potential antibacterial and anti-inflammatory functional food. © 2020 Society of Chemical Industry.
Asunto(s)
Antibacterianos/administración & dosificación , Antiinflamatorios/administración & dosificación , Camellia sinensis/química , Edema/tratamiento farmacológico , Mentha piperita/química , Extractos Vegetales/administración & dosificación , Animales , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Sinergismo Farmacológico , Edema/genética , Edema/inmunología , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Masculino , Ratones , FN-kappa B/genética , FN-kappa B/inmunología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Hojas de la Planta/química , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Staphylococcus/efectos de los fármacos , Staphylococcus/crecimiento & desarrollo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Dipsacus inermis Wall. is an edible Himalayan herb which is extensively used in traditional Ayurvedic system of medicine against various inflammation related disorders. AIM OF THE STUDY: This study was designed to evaluate the anti-inflammatory effects of Dipsacus inermis Wall. methanol extract (DIME) by using in vitro and in vivo models and to elucidate the underlying mechanism of action. MATERIALS AND METHODS: The in vitro anti-inflammatory potential of DIME was determined in LPS stimulated J774A.1â¯cells. The inhibitory effect of DIME on COX-2, PGE2 and inflammatory cytokines was determined by ELISA and RT-PCR. The suppression of ROS in response to DIME was determined by flow cytometry. Phosphorylation of NF-κBp65 and IκB degradation was determined by western blotting. RESULTS: Significant inhibition of NO, COX-2, PGE2 and pro-inflammatory cytokines including IL-1ß, TNF-α and IL-6 was found in response to DIME in LPS stimulated J774A.1â¯cells. The extract was found to down regulate the LPS induced expression of TNF-α, IL-6, iNOS and COX-2 along with inhibition of intracellular ROS. The in vivo studies carried on Wistar rats showed significant preventive effect of DIME against acetic acid induced increase in vascular permeability and carrageenan induced paw edema along with stabilization of histopathological alterations. CONCLUSION: The study demonstrated that DIME has significant in vitro and in vivo anti-inflammatory effect which is mediated by inhibiting the activation of NF-κB pathway. Our data opened a promising new pharmacological approach of designing anti-inflammatory drugs by studying individual fractions of the plant extract.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dipsacaceae , Edema/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Permeabilidad Capilar/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Edema/genética , Lipopolisacáridos/farmacología , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Hojas de la Planta , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Pleurotus pulmonarius var. stechangii is a culinary-medicinal mushroom commonly cultivated in subtropical countries in Asia. In this study, the in vitro antixanthine oxidase, antihyperglycemic, and in vivo anti-inflammatory activities of a methanol extract (ME) of P. pulmonarius var. stechangii fruiting bodies were evaluated. The xanthine oxidase inhibitory activity of the ME of P. pulmonarius var. stechangii was lower than that of allopurinol, a xanthine oxidase inhibitor used as a positive control. Eleven phenolic compounds were identified from the fruiting bodies of P. pulmonarius var. stechangii by HPLC analysis. The inhibitory effects of ME on α-amylase and α-glucosidase were moderate and lower than that of acarbose, a positive control. The ME inhibited the production of nitric oxide (NO) and nitric oxide synthases (iNOS) protein expression in lipopolysaccharide-induced RAW 264.7 macrophages. It also exhibited an inhibitory effect on carrageenan-induced hind paw edema in a rat model. Taken together, our experimental results demonstrated that the fruiting bodies of P. pulmonarius var. stechangii might be a good natural source to promote human health through its antixanthine oxidase, antihyperglycemia, and anti-inflammatory activities.
Asunto(s)
Edema/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Pleurotus/química , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Edema/genética , Edema/metabolismo , Femenino , Inhibidores de Glicósido Hidrolasas/administración & dosificación , Inhibidores de Glicósido Hidrolasas/química , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/química , alfa-Amilasas/metabolismo , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismoRESUMEN
This study evaluated the anti-inflammatory potential of a 40% prethanol extract of Trifolium pratense leaves (40% PeTP) using in vitro (RAW264.7 cells) and in vivo (carrageenan-induced inflammation model) experiments. Pretreatment with 40% PeTP significantly inhibited the LPS-induced expression of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in RAW264.7 cells, without inducing cytotoxicity. The inhibitory effects of 40% PeTP are mediated through suppression of the nuclear translocation of nuclear factor (NF)-κB and the phosphorylation of mitogen-activated protein kinases (MAPKs). Oral administration of 40% PeTP at 50, 100, and 200 mg/kg of body weight suppressed carrageenan-induced oedema in a dose-dependent manner. Collectively, our results suggested that 40% PeTP exerts potential anti-inflammatory effects by suppressing the activation of the NF-κB and MAPK pathways in vitro, and by reducing carrageenan-induced paw oedema in vivo.
Asunto(s)
Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/genética , FN-kappa B/genética , Extractos Vegetales/farmacología , Trifolium/química , Administración Oral , Animales , Carragenina/administración & dosificación , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/antagonistas & inhibidores , Dinoprostona/biosíntesis , Modelos Animales de Enfermedad , Esquema de Medicación , Edema/inducido químicamente , Edema/genética , Edema/patología , Regulación de la Expresión Génica , Inflamación , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Hojas de la Planta/química , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Lonicera japonica Thunb is a common herb in East Asia. The flower buds are usually regarded as the traditional medicinal part, while leaves and stems are considered less valuable and receive little attention. This study compared the chemical constituents and anti-inflammatory effects of the different tissues in L. japonica Thunb for the first time. RESULTS: Thirty compounds were identified by ultra-performance liquid chromatography-photodiode detector-quadrupole / time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS/MS) analysis. Hydroxycinnamic acids, flavonoids, and iridoids were identified as the major components. The flower buds (FLJ), leaves (LLJ), and stems (SLJ) of L. japonica Thunb showed strong similarities in chemical components. The LLJ contained higher levels of hydroxycinnamic acids and flavonoids than the FLJ and SLJ. Furthermore, FLJ, LLJ, and SLJ exhibited potent anti-inflammatory activity in croton oil-induced ear edema and carrageenan-induced paw edema assays in mice. Moreover, FLJ, LLJ, and SLJ showed a cytoprotective effect on lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Lipopolysaccharide-induced increases in nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were suppressed by treatments of FLJ, LLJ, and SLJ, respectively. The LLJ possessed a stronger anti-inflammatory effect than the FLJ. CONCLUSION: Leaves and stems of L. japonica Thunb have chemical components and anti-inflammatory properties similar to flower buds, and may become alternative or supplementary sources of flower buds. © 2019 Society of Chemical Industry.
Asunto(s)
Antiinflamatorios/química , Edema/tratamiento farmacológico , Lonicera/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Animales , Antiinflamatorios/administración & dosificación , Carragenina/efectos adversos , Cromatografía Líquida de Alta Presión , Edema/inducido químicamente , Edema/genética , Edema/inmunología , Flavonoides/administración & dosificación , Flavonoides/química , Flores/química , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Ratones , Hojas de la Planta/química , Tallos de la Planta/química , Espectrometría de Masas en Tándem , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Inflammation is a symptom associated with many diseases. This symptom is treated with steroidal and non-steroidal anti-inflammatory drugs, which can cause severe side effects when used as long-term treatments. Natural products are an alternative source of new compounds with anti-inflammatory activity. Jefea gnaphalioides (Astereaceae) (A. Gray) is a plant species used to treat inflammatory problems, in Mexico. This study determined the anti-inflammatory activity and the composition of the methanol extract of Jefea gnaphalioides (MEJG). METHODS: The extract was obtained by heating the plant in methanol at boiling point for 4 h, and then the solvent was evaporated under vacuum (MEJG). The derivatization of the extract was performed using Bis-(trimethylsilyl) trifluoroacetamide, and the composition was determined by GC-MS. Total Phenols and flavonoids were determined by Folin-Ciocalteu AlCl3 reaction respectively. The antioxidant activity of MEJG was determined by DPPH method. The acute and chronic anti-inflammatory effects were evaluated on a mouse ear edema induced with 12-O-Tetradecanoylphorbol-13-acetate (TPA). Acute oral toxicity was tested in mice at doses of MEJG of 5000, 2500 and 1250 mg/kg. The levels of NO, TNF-α, IL-1ß and IL-6 were determinate in J774A.1 macrophages stimulated by Lipopolysaccharide. The production of inflammatory interleukins was measured using commercial kits, and nitric oxide was measured by the Griess reaction. RESULTS: The anti-inflammatory activity of MEJG in acute TPA-induced ear edema was 80.7 ± 2.8%. This result was similar to the value obtained with indomethacin (IND) at the same dose (74.3 ± 2.8%). In chronic TPA-induced edema at doses of 200 mg/kg, the inhibition was 45.7%, which was similar to that obtained with IND (47.4%). MEJG have not toxic effects even at a dose of 5000 mg/kg. MEJG at 25, 50, 100 and 200 µg/mL decreased NO, TNF-α, IL-1ß and IL-6 production in macrophages stimulated with LPS. The major compounds in MEJG were α-D-Glucopyranose (6.71%), Palmitic acid (5.59%), D-(+)-Trehalose (11.91%), Quininic acid (4.29%) and Aucubin (1.17%). Total phenolic content was 57.01 mg GAE/g and total flavonoid content was 35.26 mg QE/g MEJG had antioxidant activity. CONCLUSIONS: MEJG has anti-inflammatory activity.
Asunto(s)
Antiinflamatorios/administración & dosificación , Asteraceae/química , Edema/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Edema/genética , Edema/inmunología , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Acanthopanax trifoliatus (L.) Merr., an edible medicinal plant from Southeast Asia, exerts a wide range of bioactivities, such as anti-inflammatory activity. However, the anti-inflammatory mechanisms of its action and active constituents remain unclear. Herein, the effects of two triterpenoids, namely impressic acid (IA) and acankoreanogenin A (AA), from A. trifoliatus in both in vitro and in vivo chronic inflammation models were investigated. The results indicated that AA and IA reduced lipopolysaccharide (LPS)-induced production of nitroxide significantly in murine macrophage RAW246.7 cells. In addition, AA and IA down-regulated the activation of NF-κB and decreased the release of inflammatory mediators (iNOS, COX-2, TNF-α, and IL-6) and tumorigenesis-associated factors (MMP-9 and VEGF) in RAW246.7 cells. Furthermore, in a tetradecanoylphorbolacetate (TPA)-treated mouse model, AA and IA could effectively attenuate mouse ear edema and pathological damage and reduced levels of cytokines including iNOS, COX-2, TNF-α, and IL-1ß. Taken together, AA and IA, being of natural origin, are promising anti-inflammatory agents and may contribute to the overall anti-inflammatory effect of A. trifoliatus.
Asunto(s)
Antiinflamatorios/administración & dosificación , Edema/tratamiento farmacológico , FN-kappa B/inmunología , Triterpenos/administración & dosificación , Animales , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Regulación hacia Abajo , Edema/genética , Edema/inmunología , Femenino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Endogámicos ICR , FN-kappa B/genética , Células RAW 264.7 , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world, and its peels are sometimes used for the treatment of cough, abdominal pain, and indigestion in China. However, the peel is discarded after fruit consumption in most cases, and its chemical constituents and biological activities have not been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared, and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema and carrageenan-induced paw edema in mice and the production of inflammatory cytokines (interleukin 1ß, prostaglandin 2, and tumor-necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results indicated that methanolic extract, ethyl acetate fraction, and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan, separately, in vivo. Furthermore, 18 coumarins inhibited inflammatory factor secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone. In summary, peel of C. grandis showed an anti-inflammatory effect and coumarin compounds were responsible for regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.
Asunto(s)
Antiinflamatorios/administración & dosificación , Citrus/química , Cumarinas/administración & dosificación , Edema/tratamiento farmacológico , Frutas/química , Extractos Vegetales/administración & dosificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Cumarinas/química , Cumarinas/aislamiento & purificación , Dinoprostona/inmunología , Edema/genética , Edema/inmunología , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Residuos/análisisRESUMEN
Mangrove ecosystems generate the major biodiversity hotspots of actinobacteria. Among the actinobacteria, Streptomyces species are the prolific producers of bioactive natural products. In this study, with research efforts to discover biopotential compounds from marine actinobacteria, 41 actinobacterial strains were isolated from sediment soil sample of Indian mangrove regions. The phylogeny prediction using the 16S rRNA gene sequences revealed that the isolates were related to Streptomyces. Isolates were further screened based on a two-step process wherein the first step, around nine strains, unveiled the presence of type 1 polyketide synthase gene and dTDP-glucose 4,6-dehydratase gene through polymerase chain reaction. As the second step of the screening process, cell viability assay was performed in RAW264.7 cells to assess the toxicity of extracts. Among all the isolates, Streptomyces rochei strain VITGAP173 was subjected to further analysis. To explore the bioactivities, the organic solvent extraction method was utilized to extract the broth culture of VITGAP173. Inhibition of nitric oxide and cyclooxygenase enzymes upon lipopolysaccharide-induced inflammation were utilized to evaluate the anti-inflammatory efficacy, and the results showed the potency of VITGAP173 in a dose-dependent manner. The extract significantly suppressed the messenger RNA levels of the inflammatory mediators such as tumor necrosis factor-α and interleukin-6 induced by lipopolysaccharide in RAW264.7 macrophages. The presence of several chemical constituents was identified through gas chromatography-mass spectrometry analysis of VITGAP173 extract. To achieve the toxicity analysis, oral administration of VITGAP173 extract in Wistar albino rats was carried out to investigate the biochemical parameters, histopathology which revealed its nontoxic nature.
Asunto(s)
Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Expresión Génica/efectos de los fármacos , Streptomyces/química , Animales , Antiinflamatorios/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo Condicionados/química , Edema/inducido químicamente , Edema/genética , Edema/patología , Femenino , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/antagonistas & inhibidores , Miembro Posterior , Interleucina-6/antagonistas & inhibidores , Interleucina-6/genética , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/antagonistas & inhibidores , Ratones , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Filogenia , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandina-Endoperóxido Sintasas/metabolismo , Células RAW 264.7 , ARN Ribosómico 16S/genética , Ratas , Ratas Wistar , Microbiología del Suelo , Streptomyces/clasificación , Streptomyces/genética , Streptomyces/metabolismo , Pruebas de Toxicidad Aguda , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética , HumedalesRESUMEN
Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1ß. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.
Asunto(s)
Antiinflamatorios/administración & dosificación , Edema/tratamiento farmacológico , Escina/administración & dosificación , Extractos Vegetales/administración & dosificación , Receptores de Glucocorticoides/inmunología , Aesculus/química , Animales , Dinoprostona/inmunología , Edema/genética , Edema/inmunología , Femenino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Anthriscus sylvestris (L.) Hoffm. is a common perennial herb that is widely distributed in Europe, Korea, and New Zealand. The root of A. sylvestris has been used in Korean traditional medicine as an antitussive and cough remedy. However, the physiologically active function of A. sylvestris leaves is not yet known. In this study, we evaluated the anti-inflammatory effects, as well as the underlying molecular mechanisms of an aqueous extract of A. sylvestris leaves (AE-ASL) in vitro and in vivo. Our results indicated that pretreatment with AE-ASL significantly inhibited the lipopolysaccharide (LPS)-induced secretion of nitric oxide (NO) and prostaglandin E2 in RAW264.7 cells, without showing cytotoxicity. In addition, the LPS-induced mRNA and protein expression of inducible NO synthase, cyclooxygenase-2, and inflammatory mediators such as tumor necrosis factor alpha interleukin (IL)-1ß, and IL-6 was attenuated by pretreatment with AE-ASL in a dose-dependent manner. Therefore, we investigated the activation of nuclear factor (NF)-κB, a transcription factor regulating the expression of inflammation-related genes. AE-ASL inhibited the nuclear translocation of the NF-κB p65 subunit by suppressing the phosphorylation and degradation of the inhibitor of NF-κB (IκBα). Further, AE-ASL inhibited the LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in RAW264.7 cells. Orally administered AE-ASL (50, 100, and 200 mg/kg of body weight [BW]) suppressed the development of carrageenan-induced rat paw edema by 15%, 31%, and 40%, respectively, after 4 h. Altogether, our results suggest that AE-ASL possesses anti-inflammatory activity, based on the suppression of NF-κB and MAPK pathways in vitro and inhibition of the carrageenan-induced paw edema in vivo.
Asunto(s)
Antiinflamatorios/administración & dosificación , Apiaceae/química , Edema/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Antiinflamatorios/química , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Dinoprostona/inmunología , Edema/genética , Edema/inmunología , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , FN-kappa B/genética , FN-kappa B/inmunología , Óxido Nítrico/inmunología , Extractos Vegetales/química , Hojas de la Planta/química , Células RAW 264.7 , Ratas , Ratas Sprague-DawleyRESUMEN
Protective effect of protodioscin or methyl protodioscin against inflammation had been reported in various inflammation diseases. This study aimed to investigate the effect of protodioscin against Complete Freund's adjuvant (CFA)-induced arthritis rats. Rats randomly divided into model groups were injected with CFA, companied with different dose of protodioscin (50, 100, and 200 mg/kg body weight). The histology, changes in biochemical parameters and inflammatory cytokines expression were detected for anti-inflammation effect evaluation of protodioscin. CFA treatment induced arthritic rats with swelling paw, ankle inflammation, and area of lymphocyte infiltration, upregulated inflammatory cytokines (IL-1ß, TNF-α, cyclo-oxygenase 2, and IL-6 as well as prostaglandin E2), articular elastase, myeloperoxidase, lipid peroxidase and nitrite oxide levels, downregulated glutathione, catalase, and superoxide dismutase. In contrast, protodioscin ameliorated all the changes induced by CFA in rats, suggesting the anti-inflammatory effect of protodioscin. We concluded that protodioscin administration into CFA-induced arthritis rats protected against CFA-induced oxidative stress, neutrophil infiltration, and inflammation, suggesting the anti-inflammatory effect and the therapeutic potential of protodioscin for arthritis.
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Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Diosgenina/análogos & derivados , Edema/tratamiento farmacológico , Regulación de la Expresión Génica/efectos de los fármacos , Saponinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Artritis Experimental/inducido químicamente , Artritis Experimental/genética , Artritis Experimental/patología , Catalasa/genética , Catalasa/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Diosgenina/farmacología , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/genética , Edema/patología , Adyuvante de Freund/administración & dosificación , Glutatión/metabolismo , Miembro Posterior , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Óxido Nítrico/metabolismo , Estrés Oxidativo , Elastasa Pancreática/genética , Elastasa Pancreática/metabolismo , Peroxidasa/genética , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-α, IL-6, and IL-1ß in RAW264.7 cells, bone marrow-derived macrophages, and THP-1 cells. TTN attenuated the LPS-induced transcriptional activity of NF-κB and decreased IκB-α and IKK phosphorylation and NF-κB/p65 nuclear translocation. Furthermore, TTN inhibited the LPS-induced transcriptional activity of AP-1, which was induced by the reduction of JNK1/2, ERK1/2, and p38MAPK phosphorylation. TTN blocked LPS-induced Toll-like receptor 4 (TLR4) dimerization, which consequently decreased MyD88 recruitment and TAK1 phosphorylation. In addition, TTN pretreatment effectively inhibited xylene-induced ear edema and LPS-induced septic death and improved LPS-induced acute kidney injury in mice. TTN exerts anti-inflammatory effects in vitro and in vivo by blocking TLR4 dimerization to activate MyD88-TAK1-NF-κB/MAPK signaling cascades, which provide the molecular basis of the anti-inflammatory effect of Danshen and suggest that TTN is a potential agent for the treatment of inflammatory diseases.
Asunto(s)
Abietanos/farmacología , Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Factor 88 de Diferenciación Mieloide/inmunología , Salvia miltiorrhiza/química , Sepsis/tratamiento farmacológico , Receptor Toll-Like 4/inmunología , Abietanos/aislamiento & purificación , Animales , Antiinflamatorios/aislamiento & purificación , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Oído , Edema/inducido químicamente , Edema/genética , Edema/inmunología , Regulación de la Expresión Génica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lipopolisacáridos/farmacología , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/inmunología , Factor 88 de Diferenciación Mieloide/genética , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/inmunología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Multimerización de Proteína , Células RAW 264.7 , Sepsis/inducido químicamente , Sepsis/genética , Sepsis/inmunología , Transducción de Señal , Células THP-1 , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/genética , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/inmunología , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Lonicera caerulea L. berry polyphenols (LCBP) are considered as major components for bioactivity. This study aimed to clarify the molecular mechanisms by monitoring inflammatory and antioxidant mediator actions in lipopolysaccharide (LPS)-induced mouse paw edema and macrophage cell model. LCBP significantly attenuated LPS-induced paw edema (3.0 ± 0.1 to 2.8 ± 0.1 mm, P < 0.05) and reduced (P < 0.05) serum levels of monocyte chemotactic protein-1 (MCP-1, 100.9 ± 2.3 to 58.3 ± 14.5 ng/mL), interleukin (IL)-10 (1596.1 ± 424.3 to 709.7 ± 65.7 pg/mL), macrophage inflammatory protein (MIP)-1α (1761.9 ± 208.3 to 1369.1 ± 56.4 pg/mL), IL-6 (1262.8 ± 71.7 to 499.0 ± 67.1 pg/mL), IL-4 (93.3 ± 25.7 to 50.7 ± 12.5 pg/mL), IL-12(p-70) (580.4 ± 132.0 to 315.2 ± 35.1 pg/mL), and tumor necrosis factor-α (TNF-α, 2045.5 ± 264.9 to 1270.7 ± 158.6 pg/mL). Cell signaling analysis revealed that LCBP inhibited transforming growth factor ß activated kinase-1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, and enhanced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and manganese-dependent superoxide dismutase (MnSOD) in earlier response. Moreover, cyanidin 3-glucoside (C3G) and (-)-epicatechin (EC), two major components of LCBP, directly bound to TAK1. These data demonstrated that LCBP might inhibit LPS-induced inflammation by modulating both inflammatory and antioxidant mediators.
Asunto(s)
Antioxidantes/administración & dosificación , Edema/tratamiento farmacológico , Mediadores de Inflamación/administración & dosificación , Lonicera/química , Extractos Vegetales/administración & dosificación , Polifenoles/administración & dosificación , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Edema/genética , Edema/inmunología , Frutas/química , Humanos , Mediadores de Inflamación/aislamiento & purificación , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Lipopolisacáridos/efectos adversos , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/inmunología , FN-kappa B/genética , FN-kappa B/inmunología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polifenoles/química , Polifenoles/aislamiento & purificaciónRESUMEN
BACKGROUND: Cheongsangbangpung-tang (CBT) is a traditional herbal formula used in Eastern Asia to treat heat-related diseases and swellings in the skin. The present study was conducted to evaluate the anti-inflammatory effects of cheongsangbangpung-tang extract (CBTE) both in vitro and in vivo. METHODS: The in vitro effects of CBTE on the lipopolysaccharide (LPS)-induced production of inflammation-related proteins were examined in RAW 264.7 cells. The levels of nitric oxide (NO) were measured with the Griess reagent. Inflammatory cytokines and prostaglandin E2 (PGE2) were detected using the enzyme-linked immunosorbent assay (ELISA) method. Inflammation-related proteins were detected by Western blot. The effect of CBTE on acute inflammation in vivo was evaluated using carrageenan (CA)-induced paw oedema. To evaluate the anti-inflammatory effect, paw oedema volume, thickness of the dorsum and ventrum pedis skin, number of infiltrated inflammatory cells, and number of COX-2-, iNOS-immunoreactive cells were measured. RESULTS: In an in vitro study, CBTE inhibited the production of NO and PGE2 and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) activity, interleukin (IL)-1ß, IL-6 and tumuor necrosis factor-α. In LPS-activated macrophages, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signalling is a pivotal pathway in the inflammatory process. These plausible molecular mechanisms increased the phosphorylation of I-κBα, while the activation of NF-κB and the phosphorylation of MAPK by LPS were blocked by CBTE treatment. In our in vivo study, a CA-induced acute oedematous paw inflammation rat model was used to evaluate the anti-inflammatory effect of CBTE. CBTE significantly reduced the increases in paw swelling, skin thicknesses, infiltrated inflammatory cells and iNOS-, COX-2 positive cells induced by CA injection. CONCLUSIONS: Based on these results, CBTE should favourably inhibit the acute inflammatory response through modulation of NF-κB activation and MAPK phosphorylation. Furthermore, the inhibition of CBTE in rat paw oedema induced by CA is considered to be clear evidence that CBTE may be a useful source to treat inflammation.
Asunto(s)
Antiinflamatorios/administración & dosificación , Edema/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/inmunología , Extractos Vegetales/administración & dosificación , Animales , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Edema/genética , Edema/inmunología , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/inmunología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Fosforilación/efectos de los fármacos , Células RAW 264.7 , Ratas , Ratas Sprague-DawleyRESUMEN
Urgent needs still exist for selective control of excessive inflammation. Despite the therapeutic potential of natural compounds against inflammation-associated chronic conditions, lack of specific molecular targets renders these bioactive compounds difficult for further development. Here we examined the bioactivity of coniferyl aldehyde (CA), a natural phenolic compound found in several dietary substances and medicinal plants, elucidating its efficacy both in vivo and in vitro with underlying molecular mechanisms. IFN-γ/TNF-α-stimulated human keratinocytes and lipopolysaccharide (LPS)-stimulated murine macrophages were used to examine the effect of CA in vitro and to elucidate the underlying mechanisms. In vivo models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and carrageenan (CRG)-induced paw edema were employed to investigate the topical and systemic anti-inflammatory effects of CA, respectively. CA significantly reduced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages. While nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways, the representative cellular pathways for iNOS induction, were not affected by CA, phosphorylation of Janus kinase 2 (JAK2) and signal Transducers and Activators of Transcription 1 (STAT1) and subsequent nuclear translocation of p-STAT1 were significantly decreased by CA. The effect of CA on JAK2-STAT1-iNOS axis was also observed in human keratinocytes stimulated with IFN-γ/TNF-α. Topical application of CA to mice produced significant protection against TPA-induced ear edema along with suppressed epidermal hyperproliferation and leucocyte infiltration. Systemic administration of CA significantly reduced CRG-induced paw edema in rats, where CRG-induced iNOS expression and STAT1 phosphorylation were decreased by CA. In summary, CA has significant anti-inflammatory properties both in vitro and in vivo, mediated by significant selective inhibition of JAK2-STAT1-iNOS signaling. CA is an attractive novel candidate for treating inflammatory diseases associated with excessive production of NO.