RESUMEN
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.
Asunto(s)
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
Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.
Asunto(s)
Clenbuterol , Modelos Animales de Enfermedad , Fibromialgia , Hiperalgesia , Atrofia Muscular , Sistema Nervioso Simpático , Animales , Femenino , Fibromialgia/patología , Fibromialgia/fisiopatología , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Hiperalgesia/fisiopatología , Hiperalgesia/patología , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/patología , Clenbuterol/farmacología , Ratas , Carragenina/toxicidad , Ratas Sprague-Dawley , Dolor/patología , Dolor/fisiopatología , Epinefrina , Músculo Esquelético/patología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Catecolaminas/metabolismo , Agonistas Adrenérgicos beta/farmacologíaRESUMEN
BACKGROUND: Inflammatory pain is caused by damaged tissue or noxious stimuli, accompanied by the release of inflammatory mediators that often leads to severe hyperalgesia and allodynia with limited therapy options. Recently, a novel mitochondrial-derived peptide (named MOTS-c) was reported to regulate obesity, metabolic homeostasis and inflammatory response. The aim of this study was to investigate the effects of MOTS-c and its related regulatory mechanisms involved in inflammatory pain. METHODS: Male Kunming mice (8-10 weeks-old) were intraplantar injected with formalin, capsaicin, λ-Carrageenan and complete Freund adjuvant (CFA) to establish acute and chronic inflammatory pain. The effects of MOTS-c on the above inflammatory pain mice and its underlying mechanisms were examined by behavioral tests, quantitative polymerase chain reaction (qPCR), western blotting, enzyme linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and immunofluorescence (IF). RESULTS: Behavioral experiments investigated the potential beneficial effects of MOTS-c on multiple acute and chronic inflammatory pain in mice. The results showed that MOTS-c treatment produced potent anti-allodynic effects in formalin-induced acute inflammatory pain, capsaicin-induced nocifensive behaviors and λ-Carrageenan/CFA-induced chronic inflammatory pain model. Further mechanistic studies revealed that central MOTS-c treatment significantly ameliorated CFA-evoked the release of inflammatory factors and activation of glial cells and neurons in the spinal dorsal horn. Moreover, peripheral MOTS-c treatment reduced CFA-evoked inflammatory responses in the surface structure of hindpaw skin, accompanied by inhibiting excitation of peripheral calcitonin gene-related peptide (CGRP) and P2X3 nociceptive neurons. CONCLUSIONS: The present study indicates that MOTS-c may serve as a promising therapeutic target for inflammatory pain.
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Capsaicina , Dolor Crónico , Ratones , Masculino , Animales , Carragenina/toxicidad , Carragenina/uso terapéutico , Capsaicina/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Hiperalgesia/metabolismo , Dolor Crónico/complicaciones , Adyuvante de Freund/toxicidad , Formaldehído/toxicidad , Formaldehído/uso terapéuticoRESUMEN
Teucrium polium (germander, Lamiaceae) is a local plant in Qatar that has been used in folk medicine to treat numerous illnesses. It is known for its antioxidant, analgesic, anticancer, and antibacterial activities. This study aimed to evaluate the anti-inflammatory activity of Teucrium polium (TP) extract by α-carrageen-induced paw edema in adult Sprague Dawley rats. The animals were randomly grouped into control, acute inflammation, and plant extract groups. Acute inflammation was induced by a sub-plantar injection of 100 µL of 1% α-carrageenan into the rat's right hind paw. Three different doses of the ethanolic extract of TP were tested at different time periods (1, 3, and 5 hours). All doses of the TP ethanolic extract showed significant inhibition of α-carrageenan-induced rat paw edema in a dose-dependent manner in both early and late phases of edema formation. The size of the α-carrageen induced paw edema was significantly reduced one, three, and five hours after TP extract injection compared to the acute inflammation group. This inhibition was accompanied by high expression of interleukin 10 (IL-10) and low expression of monocyte chemoattractant protein 1 (MCP-1), IL-1ß and tumor necrosis factor alpha (TNF-α). The results indicated that the ethanolic extracts of TP possess significant anti-inflammatory and potential pharmaceutical properties.
Asunto(s)
Teucrium , Ratas , Animales , Carragenina/toxicidad , Ratas Sprague-Dawley , Extractos Vegetales/farmacología , Antiinflamatorios/farmacología , Inflamación/inducido químicamente , Edema/inducido químicamenteRESUMEN
STOML3 is a membrane bound scaffolding protein that has been shown to facilitate the opening of mechanically sensitive ion channels and contribute to noxious mechanical sensation, allodynia and hyperalgesia. In this study, we aimed to determine the role of STOML3 in noxious mechanical sensitivity of bone afferent neurons and carrageenan-induced acute inflammation in the bone. An in vivo, electrophysiological bone-nerve preparation was used to make recordings of the activity and sensitivity of bone afferent neurons that innervate the tibial marrow cavity in anaesthetised rats, in response to noxious mechanical stimuli delivered to the marrow cavity, before and after injection of either the STOML3 oligomerisation inhibitor OB-1 or vehicle, in either naïve animals or animals with carrageenan-induced inflammation of the marrow cavity. A dynamic weight-bearing apparatus was used to measure weight bearing in response to inflammatory pain before and after injection of OB-1 or saline into the tibial marrow cavity in the presence of carrageenan-induced inflammation. Electrophysiological recordings revealed that Aδ, but not C bone afferent neurons have a reduced discharge frequency in response to mechanical stimulation, and that carrageenan-induced sensitisation of Aδ, but not C bone afferent neurons was attenuated by inhibition of STOML3 oligomerisation with OB-1. Animals treated with OB-1 spent a significantly greater amount of time on the limb injected with carrageenan than animals treated with saline. Our findings demonstrate that inhibition of STOML3 oligomerisation reduces inflammatory bone pain by reducing the sensitivity of Aδ bone afferent neurons to mechanical stimulation. Targeting STOML3 may be an effective approach to reduce pain from noxious pressure and/or painful inflammatory pathology in bone.
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Dolor Agudo , Dolor Musculoesquelético , Ratas , Animales , Carragenina/toxicidad , Carragenina/metabolismo , Ratas Sprague-Dawley , Neuronas Aferentes/metabolismo , Hiperalgesia/metabolismo , Dolor Musculoesquelético/metabolismo , Dolor Agudo/metabolismo , Modelos Animales , Inflamación/metabolismoRESUMEN
This scoping review provides an overview of publications reporting adverse effects on the intestines of the food additives carrageenan (CGN) (E 407)/processed Eucheuma seaweed (PES) (E 407a) and carboxymethylcellulose (CMC) (E 466). It includes evidence from human, experimental mammal and in vitro research publications, and other evidence. The databases Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Database of Systematic Reviews and Epistemonikos were searched without time limits, in addition to grey literature. The publications retrieved were screened against predefined criteria. From two literature searches, 2572 records were screened, of which 224 records were included, as well as 38 records from grey literature, making a total of 262 included publications, 196 on CGN and 101 on CMC. These publications were coded and analyzed in Eppi-Reviewer and data gaps presented in interactive maps. For CGN, five, 69 and 33 research publications on humans, experimental mammals and in vitro experiments were found, further separated as degraded or native (non-degraded) CGN. For CMC, three human, 20 animal and 14 in vitro research publications were obtained. The most studied adverse effects on the intestines were for both additives inflammation, the gut microbiome, including fermentation, intestinal permeability, and cancer and metabolic effects, and immune effects for CGN. Further studies should focus on native CGN, in the form and molecular weight used as food additive. For both additives, randomized controlled trials of sufficient power and with realistic dietary exposure levels of single additives, performed in persons of all ages, including potentially vulnerable groups, are needed.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Algas Marinas , Animales , Humanos , Carragenina/toxicidad , Carragenina/metabolismo , Aditivos Alimentarios/toxicidad , Aditivos Alimentarios/metabolismo , Algas Marinas/metabolismo , Carboximetilcelulosa de Sodio/toxicidad , Revisiones Sistemáticas como Asunto , Intestinos , Mamíferos/metabolismoRESUMEN
Currently, there is growing interest in exploring natural bioactive compounds with anti-inflammatory potential to overcome the side effects associated with the well-known synthetic chemicals. Algae are a rich source of bioactive molecules with numerous applications in medicine. Herein, the anti-inflammatory effect of Ulva intestinalis alone or selenium nanoparticles loaded with U. intestinalis (UISeNPs), after being fully characterized analytically, was investigated by a carrageenan-induced inflammation model. The pretreated groups with free U. intestinalis extract (III and IV) and the rats pretreated with UISeNPs (groups V and VI) showed significant increases in the gene expression of Keap1, with fold increases of 1.9, 2.27, 2.4, and 3.32, respectively. Similarly, a remarkable increase in the Nrf2 gene expression, with 2.09-, 2.36-, 2.59-, and 3.7-fold increases, was shown in the same groups, respectively. Additionally, the groups III, IV, V, and VI revealed a significantly increased HO-1 gene expression with a fold increase of 1.48, 1.61, 1.87, and 2.84, respectively. Thus, both U. intestinalis extract and the UISeNPs boost the expression of the cytoprotective/antioxidant pathway Keap1/Nrf2/HO-1, with the UISeNPs having the upper hand over the free extract. In conclusion, U. intestinalis and UISeNPs have proven promising anti-inflammatory activity through mediating different underlying mechanisms.
Asunto(s)
Nanopartículas , Selenio , Ulva , Animales , Ratas , Selenio/farmacología , Antioxidantes/farmacología , Carragenina/toxicidad , Factor 2 Relacionado con NF-E2 , Proteína 1 Asociada A ECH Tipo Kelch , EdemaRESUMEN
Pain-related aversive memory is common in chronic pain patients. Electroacupuncture has been demonstrated to block pain-related aversive memory. The insular cortex is a key region closely related to aversive behaviors. In our study, a potential mechanism underlying the effect of electroacupuncture treatment on pain-related aversive memory behaviors relative to the insular cortex was investigated. Our study used the chemogenetic method, pharmacological method, electroacupuncture intervention, and behavioral detection. Our study showed that both inhibition of gamma-aminobutyric acidergic neurons and activation of the kappa opioid receptor in the insular cortex blocked the pain-related aversive memory behaviors induced by 2 crossover injections of carrageenan in mice; conversely, both the activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex play similar roles in inducing pain-related aversive memory behaviors following 2 crossover injections of carrageenan. In addition, activation of gamma-aminobutyric acidergic neurons in the insular cortex reversed the effect of kappa opioid receptor activation in the insular cortex. Moreover, electroacupuncture effectively blocked pain-related aversive memory behaviors in model mice, which was reversed by both activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex. The effect of electroacupuncture on blocking pain-related aversive memory behaviors may be related to the activation of the kappa opioid receptor and inhibition of gamma-aminobutyric acidergic neurons in the insular cortex.
Asunto(s)
Dolor Crónico , Electroacupuntura , Ratones , Humanos , Animales , Receptores Opioides kappa/metabolismo , Corteza Insular , Carragenina/toxicidad , Neuronas GABAérgicas/fisiología , Ácido gamma-Aminobutírico/farmacología , Enfermedad Crónica , RecurrenciaRESUMEN
Plant species have been used traditionally to treat numerous inflammatory disorders because of their known medicinal properties. This study aimed to assess the anti-inflammatory effect of aqueous ethanolic leaf extract of Persicaria lanigera using acute inflammatory models. The safety profile of the Persicaria lanigera extract was assessed using an acute toxicity model. The anti-inflammatory effect of the Persicaria lanigera leaf extract (100-600 mg·kg-1, p.o.) was studied in carrageenan-induced paw oedema, zymosan-induced knee joint arthritis, and histamine-induced paw oedema in Sprague-Dawley rats (n = 5). It was observed that the Persicaria lanigera leaf extract administered prophylactically significantly inhibited paw oedema from 99.01 ± 12.59 to 59.10 ± 4.94%, 56.08 ± 3.65%, and 48.62 ± 3.27% at 100 mg·kg-1, 300 mg·kg-1, and 600 mg·kg-1, while the standard drug, aspirin, showed 41.84 ± 9.25% in carrageenan-induced paw oedema, respectively. Furthermore, the extract decreased knee joint inflammation significantly from 62.43 ± 5.73% to 32.07 ± 2.98% and 24.33 ± 8.58% at 300 mg·kg-1 and 600 mg·kg-1 in zymosan-induced knee joint inflammation, respectively. In the histamine-induced paw oedema model, the extract significantly inhibited oedema to 61.53 ± 9.17%, 54.21 ± 9.38%, and 54.22 ± 9.37% at the same doses. Aqueous ethanolic leaf extract of Persicaria lanigera is safe and attenuates inflammation in acute inflammation models.
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Extractos Vegetales , Polygonaceae , Ratas , Animales , Carragenina/toxicidad , Carragenina/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Histamina/efectos adversos , Zimosan/efectos adversos , Ratas Sprague-Dawley , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Edema/inducido químicamente , Edema/tratamiento farmacológicoRESUMEN
Diet can modulate the different stages of inflammation due to the presence of bioactive compounds such as polyphenols. Apples are a great source of phenolic compounds that show anti-inflammatory and antioxidant properties, and these might be used as a dietary supplement and/or functional element in the treatment of chronic inflammatory illnesses. The aim of our study was to evaluate the anti-inflammatory and antioxidant actions of thinned apple polyphenol (TAP) extracts in a model of paw edema. The experimental model was induced in rats via subplantar injections of 1% λ-Carrageenan (CAR) in the right hind leg, and TAP extract was administered via oral gavage 30 min before and 1 h after the CAR injection at doses of 5 mg/kg and 10 mg/kg, respectively. The inflammatory response is usually quantified by the increase in the size of the paw (edema), which is maximal about 5 h after the injection of CAR. CAR-induced inflammation generates the release of pro-inflammatory mediators and reactive oxygen species (ROS). Furthermore, the inflammatory state induces the pain that involves the peripheral nociceptors, but above all it acts centrally at the level of the spinal cord. Our results showed that the TAP extracts reduced paw histological changes, neutrophil infiltration, mast cell degranulation, and oxidative stress. Additionally, the oral administration of TAP extracts decreased thermal and mechanical hyperalgesia, along with a reduction in spinal microglia and the markers of nociception. In conclusion, we demonstrate that TAP extract is able to modulate inflammatory, oxidative, and painful processes, and is also useful in the treatment of the symptoms associated with paw edema.
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Factor 2 Relacionado con NF-E2 , FN-kappa B , Ratas , Animales , FN-kappa B/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/uso terapéutico , Polifenoles/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Carragenina/toxicidad , Inflamación/metabolismo , Extractos Vegetales/uso terapéutico , Dolor/tratamiento farmacológico , Transducción de Señal , Hiperalgesia/tratamiento farmacológico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Daniellia oliveri (Rolfe) Hutch. & Dalziel (Fabaceae) is used for the treatment of inflammatory diseases and pains (chest pain, toothache and lumbago) and rheumatism. AIM OF THE STUDY: The study investigates the anti-inflammatory and antinociceptive properties of D. oliveri and possible mechanism of antiinflammatory action. MATERIALS AND METHODS: Acute toxicity of the extract was evaluated in mice using the limit test. The anti-inflammatory activity was assessed in xylene-induced paw oedema and carrageenan-induced air-pouch models at doses of 50, 100 and 200 mg/kg, p.o. Volume of exudate, total protein, leukocyte counts, myeloperoxidase (MPO) and concentration of cytokines (TNF-α and IL-6) were measured in the exudate of rats in the carrageenan-induced air-pouch model. Other parameters include lipid peroxidation (LPO), nitric oxide (NO) and antioxidant indices (SOD, CAT and GSH). Histopathology of the air pouch tissue was also carried out. The antinociceptive effect was assessed using acetic acid-induced writhing, tail flick and formalin tests. Locomotor activity was done in the open field test. The extract was analysed with HPLC-DAD-UV technique. RESULTS: The extract showed significant anti-inflammatory effect (73.68 and 75.79%, inhibition) in xylene-induced ear oedema test at the dose of 100 and 200 mg/kg, respectively. In carrageenan air pouch model, the extract significantly reduced exudate volume, protein concentration, the migration of leukocytes and MPO production in the exudate. The concentrations of cytokines TNF-α (12.25 ± 1.80 pg/mL) and IL-6 (21.12 pg/mL) in the exudate at the dose of 200 mg/kg were reduced compared to carrageenan alone group (48.15 ± 4.50 pg/mL; 82.62 pg/mL) respectively. The extract showed significant increase in the activities of CAT and SOD and GSH concentration. The histopathological assessment of the pouch lining revealed reduction of immuno-inflammatory cell influx. Nociception was significantly inhibited by the extract in acetic acid-induced writhing model and the second phase of formalin test indicating a peripheral mechanism of action. The open field test showed that D. oliveri did not alter locomotor activity. The acute toxicity study did not cause mortality or signs of toxicity at 2000 mg/kg, p.o. We identified and quantified caffeic acid, p-coumaric acid, ferulic acid, rutin, apigenin-7-glucoside, quercetin and kaempferol in the extract. CONCLUSION: The results of our study showed that the stem bark extract of D. oliveri possesses anti-inï¬ammatory and antinociceptive activities thereby supporting its traditional use in the treatment of some inflammatory and painful disorders.
Asunto(s)
Fabaceae , Extractos Vegetales , Ratas , Ratones , Animales , Carragenina/toxicidad , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Analgésicos/uso terapéutico , Analgésicos/toxicidad , Factor de Necrosis Tumoral alfa , Xilenos/toxicidad , Corteza de la Planta/metabolismo , Interleucina-6 , Antiinflamatorios/efectos adversos , Citocinas/uso terapéutico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Superóxido DismutasaRESUMEN
OBJECTIVES: Vascular endothelial growth factor-A (VEGF-A) plays a leading role in angiogenesis and pain hypersensitivity in cancer and chronic pain. It is not only induced by ischemic conditions but is also highly correlated with proalgesic cytokines, both of which are prominent in inflammatory muscle pain. However, the molecular basis of the involvement of VEGF-A in muscle pain remains unknown. METHODS: In the present study, we performed behavioral and pharmacological analyses to determine the possible involvement of VEGF-A in the development of inflammatory muscle pain and the associated signal transduction pathway. RESULTS: Unilateral intramuscular injection of carrageenan, a classical model of inflammatory muscle pain, increased VEGF-A gene expression in the tissues surrounding the injection site. Intramuscular administration of recombinant VEGF-A165 on the same side induced cutaneous mechanical hyperalgesia during the acute and subacute phases. The application of a specific VEGFR1 antibody on the same side significantly reduced the mechanical hyperalgesia induced by carrageenan or VEGF-A165 injection, whereas both a VEGFR2-neutralizing antibody and a VEGFR2 antagonist showed limited effects. Local preinjection of capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist, also inhibited VEGF-A165-induced hyperalgesia. Finally, intramuscular VEGF-A165-induced mechanical hyperalgesia was not found in TRPV1 knockout mice during the subacute phase. CONCLUSIONS: These findings suggest that inflammatory stimuli increase interstitial VEGF-A165, which in turn induces cutaneous mechanical pain via the VEGFR1-mediated TRPV1 nociceptive pathway during inflammatory muscle pain. VEGFR1 could be a novel therapeutic target for inflammation-induced muscle pain.
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Mialgia , Factor A de Crecimiento Endotelial Vascular , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Carragenina/toxicidad , Mialgia/inducido químicamente , Canales Catiónicos TRPV/metabolismo , Hiperalgesia/metabolismo , Ratones NoqueadosRESUMEN
Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.
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Antioxidantes , Factor de Necrosis Tumoral alfa , Ratones , Animales , Carragenina/toxicidad , Antioxidantes/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Antiinflamatorios/farmacología , Estrés Oxidativo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Óxido Nítrico/metabolismoRESUMEN
Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.
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Edema , Indometacina , Animales , Antiinflamatorios/farmacología , Carragenina/uso terapéutico , Carragenina/toxicidad , Ciclooxigenasa 2/efectos adversos , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Flavonoides , Glutatión , Indometacina/farmacología , Masculino , Malondialdehído , Extractos Vegetales , Ratas , Ratas WistarRESUMEN
Alloferon-1 have been proposed as an effective peptide to enhance antitumoral immunity, antiviral defense and anti-inflammatory activity. This work aimed to assess anti-inflammatory effects of alloferon-1 against acute inflammation and histopathological deformations in λ-carrageenan-induced paw edema in mice. Systemic pretreatment with alloferon-1 (22.0 mg/kg) intraperitoneally injected mice showed a significant reduction in paw thickness and vascular permeability. Alloferon-1 prevented λ-carrageenan-evoked exudation and the neutrophil influx to the mouse pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches based on the histopathological changes in the paw tissues. Administration of alloferon-1 also suppressed the expression of the inflammatory cytokines in the inflamed paw tissues such as tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1 (MCP1), interleukin-5 (IL-5), etc. detected by Luminex liquid chip. Collectively, the present study provides evidences for the marked anti-inflammatory effects of alloferon-1 which might represent new therapeutic options for the treatment of acute inflammatory diseases.
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Interleucina-5 , Factor de Necrosis Tumoral alfa , Animales , Antiinflamatorios , Antivirales/uso terapéutico , Carragenina/toxicidad , Quimiocina CCL2 , Citocinas/uso terapéutico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Inflamación/tratamiento farmacológico , Ratones , Péptidos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Most of pharmaceutical agents exhibit several or even many biological activities. It is clear that testing even one compound for thousands of biological activities is a practically not feasible task. Therefore, computer-aided prediction is the method-of-the-choice to select the most promising bioassays for particular compounds. Using PASS Online software, we determined the likely anti-inflammatory action of the 13 dithioloquinolinethione derivatives with antimicrobial activities. Chemical similarity search in the Cortellis Drug Discovery Intelligence database did not reveal close structural analogues with anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds was comparable with or higher than the reference drug Indomethacin. Thus, based on the in silico predictions, novel class of the anti-inflammatory agents was discovered.
Asunto(s)
Antiinflamatorios , Relación Estructura-Actividad Cuantitativa , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Carragenina/uso terapéutico , Carragenina/toxicidad , Computadores , Edema/inducido químicamente , Edema/tratamiento farmacológico , Ratones , Relación Estructura-ActividadRESUMEN
Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC1, SC5, and SC10, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE2 release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE2 release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.
Asunto(s)
Coptis chinensis , Edema , Animales , Antiinflamatorios/efectos adversos , Benzofenantridinas , Carragenina/toxicidad , Edema/inducido químicamente , Edema/tratamiento farmacológico , Isoquinolinas , Masculino , RatasRESUMEN
Thrombosis, the formation of blood clots due to platelet aggregation, vascular injury or hypercoagulability, leads to cardiovascular pathologies including myocardial or cerebral infarction. Antiplatelet and thrombolytic agents have promising effects in ameliorating thromboembolism and dissolving blood clots. However, the associated limitations generate the need to explore agents from natural origin. The aim of the study was to explore the potential of aqueous methanolic extract (Sc.Cr) of an indigenous plant, Sida cordifolia L., traditionally used for cardiovascular complaints. Sc.Cr was evaluated by clot lysis assay, acute pulmonary embolism, carrageenan-induced tail vein thrombosis and ferric chloride-induced carotid arterial thrombosis models. Hemostasis parameters were increased in a dose-dependent manner. Histological studies showed restoration with clear alveolar spaces and less red blood cell congestion. Significant reduction in infarcted length of thrombus, escalation in coagulation parameters with a profound decrease in platelet count (PC) were observed. Arterial occlusion time was increased with a reduction in weight of thrombus dose-dependently with significant augmentation in PT and APTT. Sc.Cr was also analyzed for phytochemical constituents and antioxidant potential. The results demonstrated the antithrombotic and thrombolytic potential of Sc.Cr using in vitro and in vivo experimental models.
Asunto(s)
Anticoagulantes/farmacología , Extractos Vegetales/farmacología , Sida (Planta)/química , Trombosis/tratamiento farmacológico , Animales , Anticoagulantes/química , Carragenina/toxicidad , Cloruros/toxicidad , Colágeno/toxicidad , Epinefrina/toxicidad , Femenino , Compuestos Férricos/toxicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Ratas , Ratas Wistar , Trombosis/inducido químicamenteRESUMEN
Oxidative stress and inflammation play important roles in pleurisy. Leonurine (Leo) has been confirmed to exert antioxidative and antiinflammatory effects in many preclinical experiments, but these effects have not been studied in pleurisy. The aim of this study was to explore the therapeutic effect and mechanism of Leo in a carrageenan (CAR)-induced pleurisy model. In this study, we found that the increase of reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA) and decrease of glutathione (GSH) induced by CAR could be reversed by the treatment of Leo. Leo effectively reduced the levels of proinflammatory cytokines interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and the percentages of mature macrophages and increased the levels of antiinflammatory cytokines (IL-10). Furthermore, Western blotting revealed that Leo significantly activated the Nrf2 pathway to restrain the thioredoxin-interacting protein/NOD-like receptor protein 3 (TXNIP/NLRP3) and nuclear factor kappa-B (NF-κB) pathways. However, the protective effect of Leo was significantly weakened in Nrf2-deficient mice. These results indicate that Leo confers potent protection against CAR-induced pleurisy by inhibiting the TXNIP/NLRP3 and NF-κB pathways dependent on Nrf2, which may serve as a promising agent for attenuating pleurisy.
Asunto(s)
FN-kappa B , Pleuresia , Animales , Carragenina/toxicidad , Proteínas Portadoras , Ácido Gálico/análogos & derivados , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pleuresia/inducido químicamente , Pleuresia/tratamiento farmacológico , Tiorredoxinas/metabolismoRESUMEN
BACKGROUND: Curcumin is one of the compounds present in plants of the genus Curcuma sp., being very used not only as condiment but also with medicinal purposes. As an analgesic, papers highlight the efficacy of curcumin in the treatment of various types of pain. AIMS: In this study we evaluated the peripheral antinociceptive effect of curcumin and by which mechanisms this effect is induced. MAIN METHODS: The mice paw pressure test was used on animals which had increased pain sensitivity by intraplantar injection of carrageenan. All the drugs were administered in the right hind paw. KEY FINDINGS: Curcumin was administered to the right hind paw animals induced antinociceptive effect. Non -selective antagonist of opioid receptors naloxone reverted the antinociceptive effect induced by curcumin. Selective antagonists for µ, δ and κ opioid receptors clocinnamox, naltrindole and nor- binaltorphimine, respectively, reverted the antinociceptive effect induced by curcumin. Bestatin, enkephalinases inhibitor that degrade peptides opioids, did not change the nociceptive response. Selective antagonists for CB1 and CB2 cannabinoid receptors, AM251 and AM630, respectively, reversed the antinociceptive effect induced by curcumin. The MAFP inhibitor of the enzyme FAAH which breaks down anandamide, JZL184, enzyme inhibitor MAGL which breaks down the 2-AG, as well as the VDM11 anandamide reuptake inhibitor potentiated the antinociceptive effect of curcumin. SIGNIFICANCE: These results suggest that curcumin possibly peripheral antinociception induced by opioid and cannabinoid systems activation and possibly for endocannabinoids and opioids release.