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BACKGROUND: Chronic venous insufficiency (CVI) is the consequence of venous valve reflux and/or venous flow obstruction and resulting venous hypertension in the lower extremities. The aim of this prospective supplement registry study was to evaluate the efficacy of compression stockings or Pycnogenol® in controlling symptoms and edema in CVI and their efficacy on microcirculatory parameters. METHODS: Two comparable groups of 30 subjects with CVI were observed for 4 months. RESULTS: Elastic compression was less tolerated than Pycnogenol® with 12 subjects being unable to follow the compression routine. No side effects due to supplementation were observed; tolerability of the supplementation was optimal. Ambulatory venous pressure (AVP) and refilling time (RT) at inclusion indicated a significant increase in venous pressure and reflux (refilling time <16 seconds). AVP and RT did not change after 4 months. Microcirculatory and clinical measurements were comparable at inclusion between the 2 groups. After 4 months, skin resting flux (RF) and skin PO
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Edema , Flavonoides , Microcirculación , Extractos Vegetales , Medias de Compresión , Insuficiencia Venosa , Humanos , Insuficiencia Venosa/fisiopatología , Insuficiencia Venosa/tratamiento farmacológico , Flavonoides/uso terapéutico , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Masculino , Femenino , Extractos Vegetales/uso terapéutico , Edema/tratamiento farmacológico , Estudios Prospectivos , Enfermedad Crónica , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Sistema de RegistrosRESUMEN
Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.
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Antiinflamatorios , Formaldehído , Inflamación , FN-kappa B , Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Animales , FN-kappa B/metabolismo , Ratones , Factor 6 Asociado a Receptor de TNF/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Masculino , Transducción de Señal/efectos de los fármacos , Inflamación/tratamiento farmacológico , Células RAW 264.7 , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Analgésicos/uso terapéutico , Analgésicos/farmacología , Humanos , Edema/tratamiento farmacológico , Edema/inducido químicamente , Edema/inmunología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunologíaRESUMEN
C. madagascariensis, an unexplored species of Burseraceae is used by local population for the management of inflammation and throat pain. The disease alleviation by this plant could be due to the presence of rich repository of active compounds with various pharmacological importances. In this study, therefore, the profiling of metabolites and isolation of active compounds of C. madagascariensis was performed. Furthermore, the ethanol, ethyl acetate extracts and a selected active compound was subjected for in vitro and in vivo anti-inflammatory activities. Metabolomic analysis identified and quantified 116 metabolites from leaves, young stem and gum-resins of C. madagascariensis (Burseraceae) followed by multivariate PCA analysis. NMR, GC-MS and HPLC were used to analyze primary and secondary metabolites. Subsequently, five main isolated compounds were identified as trimethoxy tetrahydrobenzo dioxolo isochromene (TTDI), butyl phenol, butyl propionate phenol, germacrone and ß-elemenone. Amongst them, TTDI was found to be a novel compound. Hence, a process was developed to obtain the enriched fraction of TTDI in ethanol and ethyl acetate extracts of leaves. Furthermore, TTDI and extracts were subjected for their in vitro anti-inflammatory activity in LPS sensitized murine splenocytes. The results showed that TTDI and both extracts significantly suppressed the levels of pro-inflammatorycytokines (TNF-α, IFN-γ). Interestingly, the suppression of pro-inflammatory cytokines was evenmore significant by the similar concentration of TTDI when compared with colchicine. However, the level of anti-inflammatory cytokine (IL-10) was found to be unchanged. Additionally, in vivo anti-inflammatory study revealed a significant reduction in carrageenan induced paw edema by TTDI and both the extracts. In the docking study, TTDI was more active than colchicine with strong binding affinity to COX-2, PLA2, and 5ß reductase. Our results highlighted that the presence of metabolites with medicinal and nutraceutical importance in C. madagascariensis, could provide opportunities for the development of a new plant-based therapeutics for inflammation.
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Antiinflamatorios , Metabolómica , Extractos Vegetales , Hojas de la Planta , Animales , Hojas de la Planta/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Ratones , Masculino , Burseraceae/química , Edema/tratamiento farmacológico , Edema/metabolismo , Metaboloma/efectos de los fármacos , Citocinas/metabolismo , Cromatografía Líquida de Alta Presión/métodosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Vietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. AIM OF THE STUDY: The study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. METHODS: According to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. RESULTS: The assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 µM). CONCLUSION: The results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.
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Antiinflamatorios , Antioxidantes , Artemisia , Edema , Extractos Vegetales , Xantina Oxidasa , Animales , Xantina Oxidasa/antagonistas & inhibidores , Xantina Oxidasa/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Ratones , Células RAW 264.7 , Edema/tratamiento farmacológico , Edema/inducido químicamente , Artemisia/química , Masculino , Ácido Úrico , Flavonoides/farmacología , Óxido Nítrico/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , CarrageninaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating. AIM OF THE STUDY: To explore quality control markers of FCI based on the optimal harvest period. MATERIALS AND METHODS: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI. RESULTS: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis. CONCLUSIONS: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI.
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Antiinflamatorios , Chrysanthemum , Edema , Flores , Metabolómica , Control de Calidad , Ratas Sprague-Dawley , Animales , Chrysanthemum/química , Ratones , Metabolómica/métodos , Células RAW 264.7 , Masculino , Edema/tratamiento farmacológico , Edema/inducido químicamente , Antiinflamatorios/farmacología , Ratas , Quimiometría , Carragenina , Extractos Vegetales/farmacología , Extractos Vegetales/química , Inflamación/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , LipopolisacáridosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS) and Chuanxiong rhizoma (CR) are frequently prescribed in clinical settings for their ability to enrich blood, regulate menstrual cycles, and alleviate pain. Despite their widespread use, there is a relative dearth of studies exploring their anti-inflammatory properties. AIM OF THE STUDY: To evaluate the antioxidant and anti-inflammatory effects of Angelica sinensis-Chuanxiong rhizoma (ASCR) extracts and investigate its anti-inflammatory mechanisms. MATERIALS AND METHODS: AS and CR were combined in six ratios and extracted using five solvents. The quality of the resulting ASCR extracts was assessed by determining the content of ferulic acid (FA) using HPLC. The antioxidant effects of the ASCR extracts were evaluated in vitro using the DPPH and ABTS assays, as well as in HUVECs exposed to H2O2-induced oxidative damage. Additionally, the anti-inflammatory effects of the extracts were investigated in vivo through the assays of ear edema in mice and paw edema in rats. Biochemical markers including NO, MDA, and SOD in paw tissues, as well as PGE2, TNF-α, and COX-2 in rat serum, were measured to further elucidate the anti-inflammatory mechanisms of ASCR extracts. RESULTS: The WA-2-1 was obtained by combining AS and CR in a 2:1 ratio through first water then ethanol extraction, and showed favorable antioxidant and anti-inflammatory activities. The extract demonstrated effective scavenging abilities against DPPH⢠and ABTS+⢠radicals while also protecting against H2O2-induced oxidative damage. Furthermore, in vivo studies revealed that WA-2-1 had significant inhibitory effects on ear and paw edema as well as the ability to decrease NO and MDA levels, enhance SOD activity, and downregulate the expression of COX-2, PGE2, and TNF-α. CONCLUSIONS: The combination of AS and CR exhibits favorable anti-inflammatory effects, attributed to its dual actions of mitigating oxidative stress and suppressing the production of inflammatory mediators in serum or tissues during the inflammatory process.
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Angelica sinensis , Antiinflamatorios , Antioxidantes , Medicamentos Herbarios Chinos , Edema , Células Endoteliales de la Vena Umbilical Humana , Ratas Sprague-Dawley , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Angelica sinensis/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Humanos , Masculino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Estrés Oxidativo/efectos de los fármacos , Ratas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ligusticum/química , Peróxido de Hidrógeno , Ratones Endogámicos ICR , Rizoma , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismoRESUMEN
A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient's nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 µmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5â147 µmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 µmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.
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Edema , Glomerulonefritis Membranosa , Síndrome Nefrótico , Proteinuria , Humanos , Masculino , Adulto , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/diagnóstico , Edema/tratamiento farmacológico , Edema/diagnóstico , Rituximab/uso terapéutico , Extremidad Inferior , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
Chysobalanus icaco L. (C. icaco) is a plant that is native to tropical America and Africa. It is also found in the southeast region of Mexico, where it is used as food and to treat certain diseases. This study aimed to carry out a phytochemical analysis of an aqueous extract of C. icaco seed (AECS), including its total phenol content (TPC), total flavonoid content (TFC), and condensed tannins (CT). It also aimed to examine the antioxidant and metal-ion-reducing potential of the AECS in vitro, as well as its toxicity and anti-inflammatory effect in mice. Antioxidant and metal-ion-reducing potential was examined by inhibiting DPPH, ABTS, and FRAP. The acute toxicity test involved a single administration of different doses of the AECS (0.5, 1, and 2 g/kg body weight). Finally, a single administration at doses of 150, 300, and 600 mg/kg of the AECS was used in the carrageenan-induced model of subplantar acute edema. The results showed that the AECS contained 124.14 ± 0.32 mg GAE, 1.65 ± 0.02 mg EQ, and 0.910 ± 0.01 mg of catechin equivalents/g dried extract (mg EC/g de extract) for TPC, TFC and CT, respectively. In the antioxidant potential assays, the values of the median inhibition concentration (IC50) of the AECS were determined with DPPH (0.050 mg/mL), ABTS (0.074 mg/mL), and FRAP (0.49 mg/mL). Acute toxicity testing of the AECS revealed no lethality, with a median lethal dose (LD50) value of >2 g/kg by the intragastric route. Finally, for inhibition of acute edema, the AECS decreased inflammation by 55%, similar to indomethacin (59%, p > 0.05). These results demonstrated that C. icaco seed could be considered a source of bioactive molecules for therapeutic purposes due to its antioxidant potential and anti-inflammatory activity derived from TPC, with no lethal effect from a single intragastric administration in mice.
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Antiinflamatorios , Antioxidantes , Edema , Extractos Vegetales , Semillas , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Semillas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Carragenina/toxicidad , Flavonoides/farmacología , Flavonoides/química , Modelos Animales de Enfermedad , Pruebas de Toxicidad Aguda , Fitoquímicos/farmacología , Fitoquímicos/química , Masculino , Fenoles/química , Fenoles/farmacologíaRESUMEN
The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.
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Antiinflamatorios no Esteroideos , Liberación de Fármacos , Meloxicam , Nanopartículas , Tamaño de la Partícula , Meloxicam/administración & dosificación , Meloxicam/farmacología , Meloxicam/química , Animales , Ratas , Nanopartículas/química , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Química Farmacéutica/métodos , Masculino , Portadores de Fármacos/química , Tiazinas/administración & dosificación , Tiazinas/química , Tiazinas/farmacología , Tiazinas/farmacocinética , Poloxámero/química , Tiazoles/química , Tiazoles/farmacología , Quitosano/química , Edema/tratamiento farmacológico , Lípidos/química , Ratas Wistar , Carragenina/química , Vitamina E/química , Vitamina E/farmacología , Estabilidad de MedicamentosRESUMEN
Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC50 = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1ß. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs.
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Antiinflamatorios no Esteroideos , Inhibidores de la Ciclooxigenasa 2 , Ciclooxigenasa 2 , Simulación del Acoplamiento Molecular , Piridazinas , Piridazinas/farmacología , Piridazinas/química , Piridazinas/síntesis química , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/química , Animales , Ciclooxigenasa 2/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Humanos , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/inducido químicamente , Ratas , Masculino , Ciclooxigenasa 1/metabolismo , RatonesRESUMEN
BACKGROUND: Topical corticosteroids treat cutaneous inflammation but have side effects. In earlier studies, bilirubin exhibited anti-inflammatory effect, but its hydrophobicity and poor absorption limit its potential. AIM: Synthesis of bilirubin nanoparticles (BNP) and bilirubin nanoparticles gels (BNP gel) to study the anti-inflammatory effect of topical BNP gel against carrageenan-induced rat paw edema in Wistar rats. MATERIALS AND METHODS: BNP were synthesized, and BNP gels were prepared by mixing BNP of different concentrations with pluronic F-127 (PF-127). A different group for each formulation was assigned with five rats in each group. After 1 h of carrageenan (1% [w/v]) injection in each group, different gels were applied topically to their respective groups. Paw edema size, percent inflammation, percent edema inhibition, and inhibition time50 were evaluated. Interleukin-10 (IL-10) levels and neutrophil infiltration in rat paw tissue were evaluated by enzyme-linked immunosorbent assay and hematoxylin and eosin, respectively. RESULTS: Synthesized spherical-shaped BNP had negative zeta potential. BNP gels markedly reduced paw edema size and % inflammation as compared to carrageenan and bulk bilirubin gel (Bulk B gel) treated group and significantly increased IL-10 levels and inhibited neutrophil infiltration. CONCLUSION: BNP gels exhibited a better anti-inflammatory effect than bulk B gel and comparable anti-inflammatory potential with clobetasol.
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Antiinflamatorios , Bilirrubina , Carragenina , Edema , Geles , Interleucina-10 , Nanopartículas , Infiltración Neutrófila , Ratas Wistar , Animales , Edema/tratamiento farmacológico , Edema/inducido químicamente , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Bilirrubina/sangre , Masculino , Infiltración Neutrófila/efectos de los fármacos , RatasRESUMEN
BACKGROUND: Wounds significantly affect people's quality of life and the clinical and financial burden of healthcare systems around the world. Many of the current drugs used to treat wounds have problems such as; allergies and drug resistance. Hence, the exploration of new therapeutic agents from natural origin may avert this problem. Clerodendrum myricoides have long been used to treat wounds in Ethiopia. Despite this, nothing has so far been reported about the wound healing and anti-inflammatory activity of C. myricoides. This study aimed to evaluate the wound healing and anti-inflammatory activity of 80% methanol extract and solvent fractions of C. myricoides leaves in mice. METHODS: Leaves of C. myricoides were extracted using the maceration technique. The extract was formulated as 5% and 10% w/w ointments. The wound healing activity of the extract was evaluated using excision, incision, and burn wound models whereas the healing activities of solvent fractions were evaluated using the excision wound model. A carrageenan-induced paw edema model was used for the anti-inflammatory test. RESULTS: In the dermal toxicity test, 2000 mg/kg of 10% extract was found to be safe. In excision and burn wound models, treatment with 10% and 5% extract showed a significant (p<0.001) wound contraction. Solvent fractions of the extract significantly reduced wound contraction. A significant reduction in periods of epithelialization and favorable histopathology changes were shown by extract ointments. In incision wounds, 10% (p<0.001) and 5% (p<0.01) extracts significantly increase skin-breaking strength. After one hour of treatment, 400 mg/kg (p<0.001) and 200 mg/kg (p<0.05) showed significant reduction in paw edema. CONCLUSION: Results of this study indicate that 80% methanol extract and the solvent fraction of the leaves of C. myricoides possess wound-healing and anti-inflammatory activity and support traditional claims.
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Antiinflamatorios , Clerodendrum , Extractos Vegetales , Hojas de la Planta , Cicatrización de Heridas , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Cicatrización de Heridas/efectos de los fármacos , Hojas de la Planta/química , Ratones , Clerodendrum/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Masculino , Solventes/química , Edema/tratamiento farmacológico , Femenino , CarrageninaRESUMEN
AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.
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Administración Cutánea , Antiinflamatorios , Dexametasona , Sistemas de Liberación de Medicamentos , Edema , Iontoforesis , Agujas , Absorción Cutánea , Piel , Animales , Iontoforesis/métodos , Dexametasona/administración & dosificación , Dexametasona/farmacocinética , Dexametasona/análogos & derivados , Ratas , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Edema/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Masculino , Liberación de Fármacos , Inflamación/tratamiento farmacológico , Ratas Sprague-DawleyRESUMEN
Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer. Both in vitro and in vivo anti-inflammatory activities of the synthesized compounds were assessed relative to the positive standards: celecoxib and indomethacin. The in vitro enzymatic and transcription inhibitory actions of all the synthesized compounds were tested against cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1), and 5-lipoxygenase (LOX) and the in vivo gene expression of Interleukin-1, interleukin 10, and Tumor Necrosis Factor-α (TNF-α) were determined. The IC50 against COX-1 and COX-2 enzymes obtained by the immunoassay test revealed promising activities of sixteen compounds with selectivity indices higher than 100-fold COX-2 selectivity. Out of those, four compounds revealed selectivity indices comparable to celecoxib as a reference drug. Furthermore, all the tested compounds inhibited LOX with an IC50 in the range of 1.59-3.11 µM superior to that of the reference drug used; zileuton (IC50 = 3.50 µM). Consequently, these results highlight the promising LOX inhibitory activity of the tested compounds. The obtained in vivo paw edema results showed high inhibitory percentage for the compounds 9a, 9b, and 11a with the significant lower TNF-α relative mRNA expression for compounds 5a, 5d, 9a, 9b, 12d, and 12e. Finally, in silico docking of the most active compounds (5b, 5d, 9a, 9b) against COX2 enzymes presented an acceptable justification of the obtained in vitro inhibitory activities. As a conclusion, Compounds 5b, 5d, 9a, 9b, and 11b showed promising results and thus deserves further investigation.
Asunto(s)
Antiinflamatorios , Ciclooxigenasa 2 , Edema , Inhibidores de la Lipooxigenasa , Quinonas , Animales , Inhibidores de la Lipooxigenasa/farmacología , Ratas , Ciclooxigenasa 2/metabolismo , Edema/tratamiento farmacológico , Quinonas/farmacología , Antiinflamatorios/farmacología , Masculino , Inhibidores de la Ciclooxigenasa/farmacología , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular/métodos , Araquidonato 5-Lipooxigenasa/metabolismo , Ratas Wistar , Ciclooxigenasa 1/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , CarrageninaRESUMEN
Burns are a global health problem and can be caused by several factors, including ultraviolet (UV) radiation. Exposure to UVB radiation can cause sunburn and a consequent inflammatory response characterised by pain, oedema, inflammatory cell infiltration, and erythema. Pharmacological treatments available to treat burns and the pain caused by them include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antimicrobials and glucocorticoids, which are associated with adverse effects. Therefore, the search for new therapeutic alternatives is needed. Diosmetin, an aglycone of the flavonoid diosmin, has antinociceptive, antioxidant and anti-inflammatory properties. Thus, we evaluated the antinociceptive and anti-inflammatory effects of topical diosmetin (0.01, 0.1 and 1%) in a UVB radiation-induced sunburn model in mice. The right hind paw of the anaesthetised mice was exposed only once to UVB radiation (0.75 J/cm2) and immediately treated with diosmetin once a day for 5 days. The diosmetin antinociceptive effect was evaluated by mechanical allodynia and pain affective-motivational behaviour, while its anti-inflammatory activity was assessed by measuring paw oedema and polymorphonuclear cell infiltration. Mice exposed to UVB radiation presented mechanical allodynia, increased pain affective-motivational behaviour, paw oedema and polymorphonuclear cell infiltration into the paw tissue. Topical Pemulen® TR2 1% diosmetin reduced the mechanical allodynia, the pain affective-motivational behaviour, the paw oedema and the number of polymorphonuclear cells in the mice's paw tissue similar to that presented by Pemulen® TR2 0.1% dexamethasone. These findings indicate that diosmetin has therapeutic potential and may be a promising strategy for treating patients experiencing inflammatory pain, especially those associated with sunburn.
Asunto(s)
Antiinflamatorios , Modelos Animales de Enfermedad , Flavonoides , Inflamación , Nocicepción , Quemadura Solar , Rayos Ultravioleta , Animales , Quemadura Solar/tratamiento farmacológico , Quemadura Solar/patología , Ratones , Rayos Ultravioleta/efectos adversos , Inflamación/tratamiento farmacológico , Masculino , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Flavonoides/farmacología , Flavonoides/administración & dosificación , Nocicepción/efectos de los fármacos , Administración Tópica , Analgésicos/farmacología , Analgésicos/administración & dosificación , Edema/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológicoRESUMEN
Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H1 -receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H1-receptor blockers' ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H1-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ -carrageenan injection, all second-generation histamine H1 -receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ -carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H1 -receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine's anti-edematous activity.
Asunto(s)
Carragenina , Cetirizina , Edema , Animales , Cetirizina/farmacología , Edema/tratamiento farmacológico , Edema/inducido químicamente , Ratas , Masculino , Estereoisomerismo , Antagonistas de los Receptores Histamínicos H1/farmacología , Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacología , Relación Dosis-Respuesta a Droga , Ratas Wistar , Imidazoles/farmacología , Ratas Sprague-Dawley , DibenzazepinasRESUMEN
Some macrolide antibiotics, which share a basic lactone ring structure, also exhibit anti-inflammatory actions in addition to their antibacterial activities. However, no study has directly compared anti-inflammatory effects on acute inflammation among macrolide antibiotics with the distinct size of the lactone ring. In this study, we evaluated and compared the anti-inflammatory activities of four 14-membered macrolides (erythromycin, clarithromycin, roxithromycin, oleandomycin), one 15-membered macrolide (azithromycin), and three 16-membered macrolides (midecamycin, josamycin, leucomycin) using a rat carrageenan-induced footpad edema model. All macrolide antibiotics were intraperitoneally administered to rats one hour before the induction of inflammatory edema with 1% λ -carrageenan. The anti-inflammatory effects on acute inflammation were evaluated by changing the edema volume. All 14-membered and 15-membered macrolide antibiotics significantly suppressed the development of edema. Conversely, none of the 16-membered macrolide antibiotics inhibited the growth of edema. In conclusion, compared to 16-membered macrolide antibiotics, 14-membered and 15-membered macrolide antibiotics have stronger anti-inflammatory effects. Further research should be done to determine why different lactone ring sizes should have distinct anti-inflammatory effects.
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Antibacterianos , Antiinflamatorios , Carragenina , Edema , Inflamación , Macrólidos , Animales , Macrólidos/farmacología , Ratas , Edema/tratamiento farmacológico , Edema/inducido químicamente , Masculino , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Antiinflamatorios no Esteroideos/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens L is a wild and cultivated leguminous plant which have been used as an aphrodisiac, diuretic, nerve tonic, and antiarthritic agent. AIM: To evaluate the toxicity, antinociceptive, and anti-inflammatory activities of M. pruriens (EEMP) ethanol extract in experimental models. METHODS: M. pruriens dried leaves were extracted using aqueous ethanol (30:70). Tests for acute and subacute toxicity were conducted on rats and mice. Mice were used in hotplate, acetic acid, and formalin models to test the antinociceptive activity of EEMP. The anti-inflammatory properties of EEMP (25, 100, and 400 mg/kg) were assessed egg albumin, carrageenan, and formalin-induced oedema models. The study examined the anti-inflammatory mechanism of EEMP (25-400 mg/kg) in rats with an air pouch caused by carrageenan. Air pouch exudates were tested for total leucocytes and differential cell counts, TNF-α, IL-6, myeloperoxidase activity, malondialdehyde, nitrites, and reduced glutathione (GSH). RESULTS: The acute oral toxic dose of EEMP is greater than 2000 mg/kg. There were no significant behavioral, hematological or biochemical alterations seen after 14-days repeated administration of EEMP (200, 400 and 800 mg/kg) in mice. The EEMP demonstrated significant antinociceptive activity in hotplate, acetic acid and formalin-induced nociception in mice. The EEMP significantly and dose dependently reduced paw oedema at 2, 4 and 96 h in the egg-albumin, carrageenan- and formalin-induced paw oedema, respectively. Exudates volume, inflammatory cell counts, TNF-α, IL-6, myeloperoxidase, malondialdehyde and nitrites were significantly reduced, while GSH increased in carrageenan-air pouch of EEMP-treated rats. CONCLUSION: Mucuna pruriens leaves ethanol extract demonstrated good safety profile as well as antinociceptive and anti-inflammatory activity through mechanisms related to inhibition of oxidative stress and pro-inflammatory cytokines as well as lysosomal membrane stability.
Asunto(s)
Analgésicos , Antiinflamatorios , Edema , Mucuna , Extractos Vegetales , Hojas de la Planta , Animales , Extractos Vegetales/farmacología , Analgésicos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Masculino , Ratones , Edema/tratamiento farmacológico , Edema/inducido químicamente , Ratas , Mucuna/química , Femenino , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Carragenina , Ratas Wistar , Relación Dosis-Respuesta a Droga , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Formaldehído/toxicidad , Pruebas de Toxicidad SubagudaRESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example. AIM OF THE STUDY: The present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus). MATERIALS AND METHODS: In the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.). RESULTS: No animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56-69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25-32%, while mononuclear cell count increased by 67-74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1-63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2-40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate. CONCLUSION: SteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.