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1.
Biomed Res Int ; 2023: 2754725, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36726837

RESUMO

The present study was carried out to investigate the anti-inflammatory activity of a methanolic extract and fractions of Uvaria comperei stems. The crude extract was obtained by maceration of the powder in methanol and fractions by vacuum chromatography from the methanolic extract. To study the anti-inflammatory activity in vitro, red blood cell lysis inhibition assay and albumin denaturation inhibition were performed, while in vivo measurements of carrageenan-induced paw oedema and formalin-induced pain in albino mice were performed. Acute toxicity and cytotoxicity studies of the fraction F2 were performed, as well as its HPLC, and some biochemical parameters were quantified. Uvaria comperei crude extract (UCCE) at 250 and 500 µg/mL completely inhibited albumin denaturation, while decreasing 75.5% of heat blood cell lysis at 500 µg/mL. The fractions 128-136 (F3), 10-11 (F1), and 56-62 (F2) at 500 µg/mL displayed a significant anti-inflammatory activity with percentages of inhibition of 60.5, 67.4, and 100%, respectively. Administration of fraction F2 (25, 50, and 100 mg/kg, p.o.) produced a dose-dependent inhibition of formalin-induced pain of 60.2% at 50 mg/kg in the neurogenic phase (p < 0.05) and 70.2% at 25 mg/kg in the inflammatory phase (p < 0.05). Similarly, the time-dependent increase in carrageenan-induced paw circumference induced by carrageenan was inhibited by pretreatment with F2: 50% of inhibition at 25 mg/kg after 30 min (p < 0.05) and 96.5% inhibition at 25 mg/kg after 6 h (p < 0.05). In this research, the fraction F2 presented its maximum analgesic property at 50 mg/kg, while it presented the highest anti-inflammatory property at 25 mg/kg. The oral lethal median dose (LD50) of F2 was determined to be greater than 2000 mg/kg; further low cytotoxicity in RAW cells was also observed. Overall, this work shows that the methanolic crude extract and fractions, mainly F2, of Uvaria comperei stem have interesting anti-inflammatory properties.


Assuntos
Uvaria , Animais , Camundongos , Carragenina/efeitos adversos , Extratos Vegetais/química , Anti-Inflamatórios/uso terapêutico , Analgésicos , Dor/tratamento farmacológico , Metanol , Edema/induzido quimicamente , Edema/tratamento farmacológico
2.
J Ethnopharmacol ; 305: 116124, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36587880

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa longissima is a typical Yao ethnomedicine that has been used to treat arthritis in China. Our previous study found that the dichloromethane extract (DCME) of C. longissima showed anti-inflammatory activity in vitro. However, the anti-inflammatory mechanism and detailed chemical composition of DCME remain unclear, which lead to the original interest of this study. AIM OF THE STUDY: The study aimed to evaluate the anti-inflammatory properties of the DCME from C. longissima and further explore the accurate chemical components responsible for this active extract. MATERIALS AND METHODS: The anti-inflammatory activity of DCME in vivo was tested with carrageenan-induced mice paw edema model. Its anti-inflammatory mechanism was explored with LPS-stimulated RAW264.7 macrophages model. The compounds in DCME were isolated by repeated column chromatography and their structures were identified on the basis of nuclear magnetic resonance spectroscopy. The anti-inflammatory activities of the isolates in vitro were also tested by suppressing releases of inflammatory mediators (NO, IL-6 and TNF-α) in RAW264.7 macrophages model. In addition, the molecular docking analysis, which evaluated the potential interaction between the compounds and Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB), was performed. RESULTS: DCME effectively alleviated the mice paw edema induced by carrageenan. In LPS-stimulated RAW264.7 cells, DCME significantly decreased the production of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) via inhibiting their mRNA transcription, down-regulated the expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of alpha inhibitor of NF-κB (IκBα), NF-κB p65, and degradation of IκBα. Twelve diterpenoid phenols were identified from DCME, and they not only showed different inhibitory effects on the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells, but also could bind to TLR4 and NF-κB as analyzed by molecular docking. CONCLUSIONS: Taken together, DCME from C. longissima could inhibit inflammatory response both in vitro and in vivo, which is mainly attributed to the synergistic effect of abundant diterpenoid phenols through inhibiting the TLR4/NF-κB signaling pathway, and might be a promising agent for the treatment of inflammatory diseases.


Assuntos
Callicarpa , Diterpenos , Animais , Camundongos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Cloreto de Metileno/efeitos adversos , Interleucina-6/metabolismo , Carragenina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Transdução de Sinais , Anti-Inflamatórios/efeitos adversos , Diterpenos/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico
3.
Ecotoxicol Environ Saf ; 249: 114352, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508815

RESUMO

Chlorpyrifos-methyl (CPM) is one of the thiophosphate insecticides, and it is mainly metabolized to 3,5,6-trichloro-2-pyridinol (TCP) in the environment. As CPM is a strongly toxic and TCP is persistent in the environment, CPM and TCP need to be evaluate their toxicities using animal model organisms. With this regard, CPM and TCP were treated on zebrafish (Danio rerio) embryos and LC50 values were determined as over 2000 µg/L and 612.5 µg/L, respectively. For the hatchability, CPM did not exhibit any interference, while TCP showed weak inhibition. In the CPM-treated embryos, pericardial edema and bleeding were observed at 48 hpf, but recovered afterwards. The pericardial edema and yolk sac edema were observed in TCP-treated zebrafish embryos at the concentration of 500 µg/L after 72 hpf. TCP induced abnormal heart development and the heartbeat was dramatically decreased in Tg(cmlc2:EGFP) embryos at the level of 500 µg/L. The expression level of heart development-related genes such as gata, myl7, and cacna1c was significantly decreased in the TCP 500 µg/L-treated embryos at the 96 hpf. Taken together, TCP appears to be more toxic than the parent compound towards the zebrafish embryos. It is highly requested that TCP needs to be monitored with a strong public concern because it affects presumably heart development in early-stage aquatic vertebrates.


Assuntos
Clorpirifos , Embrião não Mamífero , Poluentes Químicos da Água , Animais , Edema/induzido quimicamente , Embrião não Mamífero/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Clorpirifos/toxicidade
4.
J Ethnopharmacol ; 303: 116021, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516907

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Colocasia esculenta (CE) (L.) Schott is an annual herbaceous tropical plant from the family of Araceae which has been traditionally used for the healing of various ailments such as asthma, arthritis, internal hemorrhage, diarrhea, and neurological disorders. The plant is reported to have potential anti-microbial, anti-fungal, antimetastatic, anti-hepatotoxic, and anti-lipid peroxidative activities. AIM OF THE STUDY: The present study is designed to explore the potential anti-inflammatory property of Colocasia esculenta methanolic root extract (CEMRE) on carrageenan-induced rat paw edema and lipopolysaccharide (LPS) stimulated RAW264.7 cells. MATERIALS AND METHODS: Carrageenan-induced rat paw edema model was used to investigate the in vivo anti-inflammatory action of CEMRE. Adult male Wistar rats (180-220 g; n = 6) were pre-treated with CEMRE (100, 200, and 400 mg/kg BW) orally before 1 h of injection of 1% carrageenan. Indomethacin (10 mg/kg BW) was given orally as the standard drug. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), nitric oxide (NO), prostaglandinE2 (PGE2), and cytokines levels were measured. Liquid chromatography-mass spectrometry (LC-MS) was done to identify the phytoconstituents present in CEMRE. The inhibitory activity of CEMRE was investigated against cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in in vitro assessment of LPS-stimulated RAW264.7 cells. The RAW 264.7 cells were pre-treated with Indomethacin (5 µM and 10 µM) and CEMRE (17 µg/ml and 34 µg/ml) followed by induction of LPS (1 µg/ml) for 24 h. Docking analyses were also performed to explore the interaction of important phytoconstituents (Sinapic acid, Acetylsalicylic acid, L-fucose, Salicylic acid, Quinic acid, Zingerone, and Gingerol) of CEMRE with COX-2 and iNOS. RESULTS: Pre-treatment with CEMRE (400 mg/kg) could inhibit the paw inflammation significantly which was elevated due to carrageenan induction. The inhibition is comparable to that of the standard drug Indomethacin. The concentration of serum AST, ALT, ALP, NO, PGE2 and cytokines were also considerably lowered in the CEMRE-treated group as compared to the carrageenan-induced group. CEMRE (34 µg/ml) inhibited the LPS-stimulated relative expression of mRNA of COX-2 and iNOS and significantly reduced the expression of nitric oxide and prostaglandin E2. Docking analyses revealed promising interaction with low binding energies between Sinapic acid with both the target proteins COX-2 and iNOS. CONCLUSION: Collectively, our results suggested that CEMRE exhibited effective anti-inflammatory actions on carrageenan-induced rat paw edema and LPS-treated RAW 264.7 cells by reducing the in vivo paw edema inhibition, inhibiting the serum NO, PGE2, cytokines and also reduced the in vitro production of NO, PGE2 along with expressions of mRNA COX-2 and iNOS. Molecular docking demonstrated good binding affinities among the target proteins and ligand Sinapic acid. Thus the bioactive compound from CE need to be isolated and purified.


Assuntos
Anti-Inflamatórios , Colocasia , Animais , Ratos , Anti-Inflamatórios/farmacologia , Carragenina , Colocasia/química , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Indometacina , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos Wistar , Células RAW 264.7 , Camundongos
5.
Int J Pharm ; 631: 122525, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36549402

RESUMO

Pain and inflammation could have a negative impact on a patient's quality of life and performance, causing them to sleep less. Dexketoprofen trometamol (DKT) is a water-soluble, nonselective NSAIDs. Because DKT is quickly eliminated in the urine after oral delivery, its efficacy is limited and must be taken repeatedly throughout the day. The main ambition of this work is to develop and characterize the potential of invasomes to enhance the transdermal transport of DKT to achieve efficient anti-inflammatory and pain management. The optimum formulation (C1) showed the least %RE (53.29 ± 2.68 %), the highest %EE (86.51 ± 1.05 %), and spherical nanosized vesicles (211.9 ± 0.57 nm) with (PDI) of 0.353 ± 0.01 and (ZP) of -19.15 ± 2.45 mV. DKT flux and deposition in stratum corneum, epidermal, and dermal skin layers were significantly augmented by 2.6 and 3.51 folds, respectively, from the optimum invasomal gel formulation (C1-G) compared to DKT conventional gel (DKT-G). The anti-inflammatory activity of C1-G was evaluated using a model of xylene-induced ear edema in rats. Xylene exposure upregulated the ear expression of COX-2 level and MPO activity. Xylene also significantly increased the ear NF-κB p65, TNF-α, IL-Iß, and MDA levels. Furthermore, xylene induced oxidative stress, as evidenced by a significant decrease in ear GSH and serum TAC levels. These impacts were drastically improved by applying C1-G compared to rats that received DKT-G and plain invasomal gel formulation (plain C1-G). The histopathological findings imparted substantiation to the biochemical and molecular investigations. Thereby, C1-G could be a promising transdermal drug delivery system to improve the anti-inflammatory and pain management of DKT.


Assuntos
NF-kappa B , Xilenos , Ratos , Animais , NF-kappa B/metabolismo , Ciclo-Oxigenase 2/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Qualidade de Vida , Anti-Inflamatórios/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Estresse Oxidativo
6.
Biotechnol Lett ; 45(2): 235-253, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36550336

RESUMO

Baicalein (BA) is a flavonoid with wide-ranging pharmacological activity. However, its biological evaluation is hampered by its low solubility in aqueous medium, making forms of incorporation that improve its solubility necessary. In the present study, BA was combined with a solution of silk fibroin protein (SF), a biomaterial used too as a drug carrier, to evaluate the anti-inflammatory potential of this combination, in vivo, in an experimental model, zebrafish (Danio rerio). Baicalein-silk fibroin (BASF) improved the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging rate (95%) in comparison with BA in solution. The acute toxicity study and histopathological analysis in zebrafish showed that BASF has low cytotoxic potential, except for the maxim dose of 2000 mg/kg. The use of BA in combination with SF enhanced the anti-inflammatory effect of flavonoids by inducing inflammatory peritoneal edema through carrageenan and achieved 77.6% inhibition of abdominal edema at a dose of 75 mg/kg. The results showed that the BASF, significantly increases the bioavailability and therapeutic effect of flavonoids and several results observed in this study may help in the development of new drugs.


Assuntos
Fibroínas , Animais , Fibroínas/farmacologia , Peixe-Zebra , Flavonoides , Anti-Inflamatórios/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Seda
7.
J Ethnopharmacol ; 305: 116017, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36529252

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The seed of the African walnut, Plukenetia conophora Mull.-Arg is well-known for its nutritional and medicinal values. The seed oil is widely used in massages to relieve pain, as nerve tonic and to enhance sexual performance. OBJECTIVE: The study aimed at investigating the chemical profile, antinociceptive and anti-inflammatory activities of P. conophora oil (PCO). METHODS: Seed oil of P. conophora was characterized using Gas-Liquid Chromatographic method (GC-MS) and oral acute toxicity evaluated at 2000 mg/kg. Antinociceptive effects were evaluated in hot plate, acetic acid and formalin-induced paw licking tests. The anti-inflammatory effects were investigated in egg albumin and carrageenan-, formalin and complete Freund adjuvant (CFA)-induced paw oedema models. The levels of pro-inflammatory cytokines in the fluid exudates were also evaluated in carrageenan air pouch model. RESULTS: PCO exhibited high content of alpha linolenic acid (ALA). No toxicity was observed at 2000 mg/kg of PCO. PCO (50-200 mg/kg) demonstrated significant anti-nociceptive activity in pain models. PCO exhibited anti-inflammatory activity against oedema formation by phlogistic agents. The increased inflammatory oedema and oxidative stress in CFA-treated rats were also attenuated by PCO. The PCO (100 and 200 mg/kg) significantly reduced the levels of TNF-α (59.3% and 85.2%) and IL-6 (27.5% and 72.5%) in carrageenan-induced air pouch model. CONCLUSION: The results of this study suggest that ALA-rich seed oil of Plukenetia conophora demonstrated anti-nociceptive and anti-inflammatory activities via inhibition of pro-inflammatory cytokines and oxidative stress, lending supportive evidences for its use in painful inflammatory conditions.


Assuntos
Analgésicos , Extratos Vegetais , Ratos , Animais , Carragenina , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Extratos Vegetais/farmacologia , Roedores , Anti-Inflamatórios/efeitos adversos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Citocinas/uso terapêutico , Formaldeído , Óleos Vegetais/efeitos adversos , Sementes , Edema/induzido quimicamente , Edema/tratamento farmacológico
8.
J Ethnopharmacol ; 303: 116019, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36493996

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The infusion of Serjania erecta Radlk (Sapindaceae) (popular name "cipó-cinco-folhas") leaves is used in popular medicine to treat back pain. The anti-inflammatory, anti-hyperalgesic and anti-nociceptive properties of the ethanolic extract from S. erecta leaves (EESE) has not been yet completely clarified. AIM OF THE STUDY: The present study investigated the anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties of EESE in experimental models in mice. MATERIAL AND METHODS: EESE was fractionated by chromatographic techniques and the compound was identified by nuclear magnetic resonance (NMR), infrared (IR) spectrum, ultraviolet (UV) methods. Mice received a single dose of EESE by oral route (30, 100, and 300 mg/kg, p.o.) and were submitted to nociception induced by formalin, pleurisy induced by carrageenan and peritonitis induced by zymosan models. Mice also received EESE (30 and 100 mg/kg, p.o.) for 22 days in Complete Freund Adjuvant (CFA) model and another group received EESE for 7 days (30 and 100 mg/kg, p.o.) in pleurisy induced by Bacillus Calmette-Guerin (BCG). The cytotoxicity (MTT), phagocytic and chemotactic inhibitory activities of EESE were performed in in vitro assays. RESULTS: The fractionation of EESE led to the identification of kaempferol-3-O-α-L-rhamnopyranoside. The oral administration of all doses of EESE decreased the nociceptive response induced by formalin. EESE significantly inhibited leukocyte migration in carrageenan-induced pleurisy and zymosan peritonitis models. The daily administration of EESE during for 7 days inhibited the leukocyte migration and the mycobacteria growth of pleural material obtained from animals which received BCG. EESE significantly reduced edema, cold allodynia and mechanical hyperalgesia responses induced by CFA. EESE did not induce cytotoxicity, and also decreased the leukocyte phagocytic activity, as well as, neutrophil chemotaxis. CONCLUSIONS: EESE showed analgesic and anti-inflammatory properties in acute and persistent experimental models in mice. EESE also reduced in vitro leukocyte chemotaxis and phagocytic activity without inducing cytotoxicity. The continuous oral treatment with EESE was effective against hyperalgesia and inflammation and these results could explain the popular use of S. erecta as an analgesic natural agent.


Assuntos
Analgésicos , Anti-Inflamatórios , Extratos Vegetais , Animais , Camundongos , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Vacina BCG , Carragenina , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Etanol , Formaldeído , Hiperalgesia/tratamento farmacológico , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Sapindaceae/química , Zimosan
9.
Bioorg Med Chem Lett ; 80: 129101, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36481449

RESUMO

In this study, a series of structurally novel N-(benzene sulfonyl) acetamide derivatives were designed, synthesized, and biologically evaluated as COX-2/5-LOX/TRPV1 multitarget inhibitors for anti-inflammatory and analgesic therapy. Among them, 9a and 9b displayed favorable COX-2 (9a IC50 = 0.011 µM, 9b IC50 = 0.023 µM), 5-LOX (9a IC50 = 0.046 µM, 9b IC50 = 0.31 µM) and TRPV1 (9a IC50 = 0.008 µM, 9b IC50 = 0.14 µM) inhibitory activities. The pharmacokinetic (PK) study of 9a in SD rats at the dosage of 10 mg/kg demonstrated a high oral exposure, an acceptable clearance and a favorable bioavailability (Cmax = 5807.18 ± 2657.83 ng/mL, CL = 3.24 ± 1.47 mL/min/kg, F = 96.8 %). Further in vivo efficacy studies illustrated that 9a was capable of ameliorating formalin-induced pain and inhibiting capsaicin-induced ear edema.


Assuntos
Analgésicos , Benzeno , Ratos , Animais , Ciclo-Oxigenase 2/metabolismo , Ratos Sprague-Dawley , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Amidas/uso terapêutico , Acetamidas/farmacologia , Acetamidas/uso terapêutico , Relação Estrutura-Atividade , Edema/induzido quimicamente , Edema/tratamento farmacológico , Simulação de Acoplamento Molecular , Anti-Inflamatórios não Esteroides/farmacologia , Canais de Cátion TRPV
10.
J Ethnopharmacol ; 305: 116084, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36584922

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ji-Ming-Shan (JMS) is a traditional herbal prescription consisting of seven herbs including Areca cathechu Burm.f., Citrus reticulata Blanco, Chaenomeles speciosa (Sweet) Nakai, Euodia ruticarpa (A. Juss.) Benth., Perilla frutescens (L.) Britton, Zingiber officinale Roscoe, Platycodon grandiflorus (Jacq.). It was first recorded during the Song dynasty and has been used extensively for protection against rheumatism, treatment of swelling of tendons, relief from foot pain, gout and diuresis and other forms of inflammation. AIM OF THE STUDY: The aim of this study is to evaluate the anti-inflammatory and anti-osteoarthritis activity of JMS extracts with the use of different cell lines (RAW 264.7 cells, SW1353 cells and primary cultured rat chondrocytes). MIA-induced rat animal models were used to assess the anti-osteoarthritis activity of the extract. MATERIALS AND METHODS: This study investigated the anti-inflammatory activity of JMS-95E on LPS-induced RAW 264.7 macrophages and IL-1ß-stimulated chondrocytes. For the in vivo study, male Wistar rats were used and they were randomly assigned in different groups: blank, control, positive control and three different JMS-95E treatment groups (200, 400, 800 mg/kg/d). Paw edema, hind-limb weight bearing, serum inflammatory cytokines including hematoxylin and eosin (HE) staining experiments were used to assess the efficacy of the extract in the rat model. RESULT: JMS 95% ethanol extract (JMS-95E, marker substance: narirutin (5.10 mg/g) and hesperidin (11.33 mg/g) has been identified in the extract using high pressure liquid chromatography. For in vitro assays, JMS-95E did not exhibit cytotoxicity and was able to downregulate the protein expression of iNOS, COX-2 and MMP-13. The production of inflammatory mediators such as NO and PGE2 were also reduced with an increase in dose-dependent manner in various cell lines. Inhibitory activity on the key enzyme xanthine oxidase was also observed in this study. In rat animal models, JMS-95E reduced the inflammatory responses such as acute swelling, chondrocyte degradation and pain section of paw edema in rat model. Molecular marker studies of inflammation demonstrated that JMS-95E significantly decrease PGE2 expression in MIA model. CONCLUSION: JMS-95E inhibited the inflammatory pathway leading to the production or expression levels of NO, iNOS, COX-2 and PGE2 in macrophage cells. In primary cultured rat chondrocytes iNOS and SW1353 MMP-13 expression were downregulated after JMS-95E treatment. For the in vivo study JMS-95E significantly reduced the paw volume of carrageenan-induced rat paw edema through each dose and significantly inhibited paw volume, counterweight the distribution of hind-paw weight bearing through the MIA model which means JMS-95E could promote recovery of the acute swelling and chondrocyte degradation of the ankle joints. The above results provided the multiple mechanism of JMS-95E in OA treatment of the scientific founding which supported the description of JMS in traditional use.


Assuntos
Osteoartrite , Animais , Masculino , Ratos , Anti-Inflamatórios/efeitos adversos , Carragenina , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/prevenção & controle , Inflamação/tratamento farmacológico , Metaloproteinase 13 da Matriz , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/efeitos adversos , Ratos Sprague-Dawley , Ratos Wistar
11.
Int J Biol Macromol ; 228: 659-670, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36584776

RESUMO

A novel series of twenty two flurbiprofen amides (1-22) were designed and synthesized in good to excellent yields by reacting flurbiprofen acid with various aromatic/aliphatic primary amines in the presence of 1,1­carbonyldiimidazole (CDI) in basic medium using acetonitrile as solvent. Structures of the synthesized derivatives were elucidated with the help of HR-ESI-MS, 1H-, and 13C NMR spectroscopy and finally screened them for their in-vivo anti-inflammatory potential using carrageenan induced mice paw oedema assay. Among the series, four compounds (8, 14, 15, and 20) displayed excellent activity ranging from 59.0 to 77.7 % decrease, while eight compounds (1, 3, 7, 10, 12, 13, 17, and 18) exhibited good activity in the decrease range of 37.0-50.0 %. Additionally, four compounds (2, 6, 16, and 22) attributed less activity, while the remaining six compounds (4, 5, 9, 11, 19, and 21) were found to be inactive. Furthermore, the In-silico studies were executed on the synthesized derivatives in order to explain the binding interface of compounds with the active sites of prostaglandin endoperoxide-synthase II enzyme.


Assuntos
Flurbiprofeno , Camundongos , Animais , Flurbiprofeno/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Simulação de Acoplamento Molecular , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2 , Relação Estrutura-Atividade , Anti-Inflamatórios não Esteroides/química , Estrutura Molecular , Edema/induzido quimicamente , Edema/tratamento farmacológico , Carragenina
12.
Int J Mol Sci ; 23(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36499338

RESUMO

Inflammation is implicated in a wide variety of physiological and pathological processes. Plants are an important source of active anti-inflammatory compounds. The compound 3, 5-diprenyl-4-hydroxyacetophenone (DHAP) was isolated from the dichloromethane extract of the aerial parts of Ageratina pazcuarensis by chromatography and identified by spectroscopic (IR, NMR) and spectrometric (GC-MS) methods. Anti-inflammatory activity was evaluated on ear edema mouse induced with 12-O-tetradecanoylphorbol 13-acetate (TPA) at 2 mg/ear. The antioxidant activity of DHAP was determined using DPPH assay. Cell viability was tested in J774A.1 macrophages, the levels of NO, TNF-α, IL-1ß, IL-6, and IL-10 production in macrophages stimulated with lipopolysaccharide (LPS), and membrane lysis induced by hypotonic solution in erythrocytes were evaluated. DHAP diminished the ear edema mouse in 70.10%, and it had scavenger effect against the radical with IC50 of 26.00 ± 0.37 µg/mL. Likewise, 91.78 µM of this compound inhibited the production of NO (38.96%), IL-1ß (55.56%), IL-6 (51.62%), and TNF-α (59.14%) in macrophages and increased the levels of IL-10 (61.20%). Finally, 25 and 50 µg/mL DHAP provided the greatest protection against erythrocyte membrane lysis. These results demonstrate that DHAP has anti-inflammatory activity.


Assuntos
Ageratina , Anti-Inflamatórios , Extratos Vegetais , Animais , Camundongos , Ageratina/química , Anti-Inflamatórios/farmacologia , Edema/induzido quimicamente , Interleucina-10 , Interleucina-6 , Lipopolissacarídeos , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa
13.
Gan To Kagaku Ryoho ; 49(12): 1355-1359, 2022 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-36539249

RESUMO

Docetaxel(DTX)is a key drug for breast cancer treatment; however, its formulation contains alcohol, which can cause several problems. We have been preparing original DTX without using its accompanying alcohol-solubilizing solution since 2013 and switched to generic DTX without alcohol in 2015. In this study, we compared adverse events between the original and generic DTX, both of which did not contain alcohol. We retrospectively investigated the occurrence of adverse events in breast cancer patients who were treated with DTX(75 mg/m2)as neoadjuvant or adjuvant chemotherapy from January 2013 to December 2017. 201 patients participated in the study(75/126 in the original/generic groups). The incidence of febrile neutropenia, hypersensitivity reactions, and skin toxicities did not differ between the groups(p=0.620, 0.066, 0.205). The severity of edema and peripheral neuropathy was significantly worse in the patients receiving the generic DTX (p<0.01, <0.01). The findings suggest a difference in the incidence of edema and peripheral neuropathy following treatment with the original and generic DTX, regardless of the inclusion of alcohol.


Assuntos
Antineoplásicos , Neoplasias da Mama , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Docetaxel/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Taxoides/efeitos adversos , Etanol/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Edema/induzido quimicamente , Edema/tratamento farmacológico , Antineoplásicos/uso terapêutico
14.
Molecules ; 27(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500568

RESUMO

In this study, 1-methylhydantoin cinnamic imides were synthesized from 1-methylhydantoin and trans-cinnamic acid, and their anti-inflammatory activity was investigated. The anti-inflammatory activity in vitro was evaluated by measuring the contents of NO, TNF-α and IL-1ß in the supernatant of RAW264.7 cells stimulated by LPS. The cytotoxicity of 1-methylhydantoin cinnamoyl imides on RAW264.7 cells was detected using the CCK-8 method. The results showed that compounds 2 and 4 can significantly inhibit the release of NO and reduce the secretion of TNF-α and IL-1ß. Compound 3 inhibited the production of TNF-α. The inhibition rate of COX was evaluated in vitro. The in vivo anti-inflammatory activities of the five compounds were evaluated by establishing an animal model of xylene ear swelling. The results showed that 1-methylhydantoin cinnamic imides could alleviate xylene-induced ear edema in mice in a dose-dependent manner. Among them, the effect of compound 5 was the most significant. Under the action of high dosage, its ear swelling inhibition rate was as high as 52.08%.


Assuntos
Imidas , Fator de Necrose Tumoral alfa , Camundongos , Animais , Fator de Necrose Tumoral alfa/efeitos adversos , Imidas/uso terapêutico , Extratos Vegetais/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Células RAW 264.7 , Lipopolissacarídeos/efeitos adversos
15.
Molecules ; 27(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36500682

RESUMO

Snakebite is a neglected tropical disease that causes extensive mortality and morbidity in rural communities. Antivenim sera are the currently approved therapy for snake bites; however, they have some therapeutic limitations that have been extensively documented. Recently, small molecule toxin inhibitors have received significant attention as potential alternatives or co-adjuvant to immunoglobulin-based snakebite therapies. Thus, in this study, we evaluated the inhibitory effects of the phospholipase A2 inhibitor varespladib and the metalloproteinase inhibitor CP471474 and their synergistic effects on the lethal, edema-forming, hemorrhagic, and myotoxic activities of Bothrops asper and Crotalus durissus cumanensis venoms from Colombia. Except for the preincubation assay of the lethal activity with B. asper venom, the mixture showed the best inhibitory activity. Nevertheless, the mix did not display statistically significant differences to varespladib and CP471474 used separately in all assays. In preincubation assays, varespladib showed the best inhibitory activity against the lethal effect induced by B. asper venom. However, in independent injection assays, the mix of the compounds partially inhibited the lethal activity of both venoms (50%). In addition, in the assays to test the inhibition of edema-forming activity, the mixture exhibited the best inhibitory activity, followed by Varespladib, but without statistically significant differences (p > 0.05). The combination also decreased the myotoxic activity of evaluated venoms. In these assays, the mix showed statistical differences regarding CP471474 (p < 0.05). The mixture also abolished the hemorrhagic activity of B. asper venom in preincubation assays, with no statistical differences to CP471474. Finally, the mixture showed inhibition in studies with independent administration in a time-dependent manner. To propose a mode of action of varespladib and CP471474, molecular docking was performed. PLA2s and SVMPs from tested venoms were used as targets. In all cases, our molecular modeling results suggested that inhibitors may occupy the substrate-binding cleft of the enzymes, which was supported by specific interaction with amino acids from the active site, such as His48 for PLA2s and Glu143 for the metalloproteinase. In addition, varespladib and CP471474 also showed interaction with residues from the hydrophobic channel in PLA2s and substrate binding subsites in the SVMP. Our results suggest a synergistic action of the mixed inhibitors and show the potential of varespladib, CP471474, and their mixture to generate new treatments for snakebite envenoming with application in the field or as antivenom co-adjuvants.


Assuntos
Bothrops , Venenos de Crotalídeos , Mordeduras de Serpentes , Animais , Simulação de Acoplamento Molecular , Venenos de Crotalídeos/toxicidade , Antivenenos/farmacologia , Antivenenos/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Metaloproteases , Hemorragia/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico
16.
Molecules ; 27(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36364031

RESUMO

Agave angustifolia is a xerophytic species widely used in Mexico as an ingredient in sweet food and fermented beverages; it is also used in traditional medicine to treat wound pain and rheumatic damage, and as a remedy for psoriasis. Among the various A. angustifolia extracts and extract fractions that have been evaluated for their anti-inflammatory effects, the acetonic extract (AaAc) and its acetonic (F-Ac) and methanolic (F-MeOH) fractions were the most active in a xylene-induced ear edema model in mice, when orally administered. Four fractions resulting from chemically resolving F-Ac (F1-F4) were locally applied to mice with phorbol 12-myristate 13-acetate (TPA)-induced ear inflammation; F1 inhibited inflammation by 70% and was further evaluated in a carrageenan-induced mono-arthritis model. When administered at doses of 12.5, 25, and 50 mg/kg, F1 reduced articular edema and the spleen index. In addition, it modulated spleen and joint cytokine levels and decreased pain. According to a GC-MS analysis, the main components of F1 are fatty-acid derivatives: palmitic acid methyl ester, palmitic acid ethyl ester, octadecenoic acid methyl ester, linoleic acid ethyl ester, and oleic acid ethyl ester.


Assuntos
Agave , Camundongos , Animais , Anti-Inflamatórios/uso terapêutico , Extratos Vegetais/uso terapêutico , Ácidos Graxos/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Carragenina/efeitos adversos , Dor/tratamento farmacológico , Ésteres , Fitoterapia
18.
Biomolecules ; 12(11)2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36421718

RESUMO

A novel peptide AnmTX Sco 9a-1 with the ß-hairpin fold was isolated from the swimming sea anemone Stomphia coccinea (Actinostolidae family). The peptide consists of 28 amino acid residues, including modified hydroxyproline residue, and its measured molecular mass is 2960 Da. The peptide was not toxic on mice; however, it stimulated their exploratory motivation and active search behavior, and demonstrated an anti-anxiety effect. AnmTX Sco 9a-1 at doses of 0.1 and 1 mg/kg reduced the volume of edema during 24 h better than the nonsteroidal anti-inflammatory drug, Diclofenac, at dose of 1 mg/kg in a model of acute local λ-carrageenan-induced inflammation. ELISA analysis of the animal's blood showed that peptide at a dose of 1 mg/kg reduced the content of tumor necrosis factor-α (TNF-α), a pro-inflammatory mediator responsible in the edema development, up to the level of TNF-α in the intact group. Besides, AnmTX Sco 9a-1 demonstrated a significant analgesic effect on acute pain sensitivity in the carrageenan-induced thermal hyperalgesia model at doses of 0.1 and 1 mg/kg. Activity of AnmTX Sco 9a-1 was shown not to be associated with modulation of nociceptive ASIC channels.


Assuntos
Peptídeos , Anêmonas-do-Mar , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Edema/induzido quimicamente , Edema/tratamento farmacológico , Peptídeos/química , Anêmonas-do-Mar/química , Fator de Necrose Tumoral alfa
19.
Molecules ; 27(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36431841

RESUMO

The species Trattinnickia rhoifolia Willd, (T.&nbsp;rhoifolia), which belongs to the Burseraceae family, is widely used in ethnopharmacological cultural practices by traditional Amazonian people for anti-inflammatory purposes, sometimes as their only therapeutic resource. Although it is used in teas, infusions, macerations and in food, the species is still unexplored in regard to its pharmacophoric potential and chemical profile. Therefore, the aim of this study was to conduct a phytochemical characterization of the hydroethanolic extract of T. rhoifolia leaves (HELTr) and to evaluate the acute toxicity and anti-inflammatory activity of this species using zebrafish (Danio rerio). The extract was analyzed by gas chromatography-mass spectrometry (GC-MS). The evaluation of the acute toxicity of the HELTr in adult zebrafish was determined using the limit test (2000 mg/kg), with behavioral and histopathological evaluations, in addition to the analysis of the anti-inflammatory potential of HELTr in carrageenan-induced abdominal edema, followed by the use of the computational method of molecular docking. The phytochemical profile of the species is chemically diverse, suggesting the presence of the fatty acids, ester, alcohol and benzoic acid classes, including propanoic acid, ethyl ester and hexadecanoic acid. In the studies of zebrafish performed according to the index of histopathological changes (IHC), the HELTr did not demonstrate toxicity in the behavioral and histopathological assessments, since the vital organs remained unchanged. Carrageenan-induced abdominal edema was significantly reduced at all HELTr doses (100, 200 and 500 mg/kg) in relation to the negative control, dimethyl sulfoxide (DMSO), while the 200 mg/kg dose showed significant anti-inflammatory activity in relation to the positive control (indomethacin). With these activities being confirmed by molecular docking studies, they showed a good profile for the inhibition of the enzyme Cyclooxygenase-2 (COX-2), as the interactions established at the sites of the receptors used in the docking study were similar to the controls (RCX, IMN and CEL). Therefore, the HELTr has an acceptable degree of safety for acute toxicity, defined in the analysis of behavioral changes, mortality and histopathology, with a significant anti-inflammatory action in zebrafish at all doses, which demonstrates the high pharmacophoric potential of the species. These results may direct future applications and drug development but still require further elucidation.


Assuntos
Burseraceae , Peixe-Zebra , Animais , Carragenina/efeitos adversos , Simulação de Acoplamento Molecular , Anti-Inflamatórios/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Ésteres
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