RESUMO
Astaxanthin is a natural C40 carotenoid with numerous reported biological functions, most of them associated with its antioxidant and anti-inflammatory activity, standing out from other antioxidants as it has shown the highest oxygen radical absorbance capacity (ORAC), 100-500 times higher than âº-tocopherol and a 10 times higher free radical inhibitory activity than related antioxidants (α-tocopherol, α-carotene, ß -carotene, lutein and lycopene). In vitro and in vivo studies have associated astaxanthin's unique molecular features with several health benefits, including neuroprotective, cardioprotective and antitumoral properties, suggesting its therapeutic potential for the prevention or co-treatment of dementia, Alzheimer, Parkinson, cardiovascular diseases and cancer. Benefits on skin and eye health promotion have also been reported, highlighting its potential for the prevention of skin photo-aging and the treatment of eye diseases like glaucoma, cataracts and uveitis. In this review, we summarize and discuss the currently available evidence on astaxanthin benefits, with a particular focus on human clinical trials, including a brief description of the potential mechanisms of action responsible for its biological activities.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Descoberta de Drogas , Humanos , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Xantofilas/farmacocinética , Xantofilas/farmacologia , Xantofilas/uso terapêuticoRESUMO
Andrographolide is a labdane diterpene and the main active ingredient isolated from the herb Andrographis paniculata. Andrographolide possesses diverse biological effects including anti-inflammatory, antioxidant, and antineoplastic properties. Clinical studies have demonstrated that andrographolide could be useful in therapy for a wide range of diseases such as osteoarthritis, upper respiratory diseases, and multiple sclerosis. Several targets are described for andrographolide, including the interference of transcription factors NF-κB, AP-1, and HIF-1 and signaling pathways such as PI3K/Akt, MAPK, and JAK/STAT. In addition, an increase in the Nrf2 (nuclear factor erythroid 2-related factor 2) signaling pathway also supports its antioxidant and anti-inflammatory properties. However, this scenario could be more complex since recent evidence suggests that andrographolide targets can modulate glucose metabolism. The metabolic effect of andrographolide might be the key to explaining the diverse therapeutic effects described in preclinical and clinical studies. This review discusses some of the most recent evidence about the anti-inflammatory and metabolic effects of andrographolide.
Assuntos
Anti-Inflamatórios/farmacocinética , Diterpenos/farmacocinética , Animais , Anti-Inflamatórios/química , Biomarcadores , Diterpenos/química , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Transdução de Sinais/efeitos dos fármacos , Distribuição TecidualRESUMO
This study presents the development and validation of a fast and simple bioanalytical ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method intended for quantifying the anti-inflammatory candidate 5'-methoxynobiletin (5'-MeONB) in rat plasma. Standard of 5'-MeONB was purified from A. conyzoides extract by using preparative HPLC. After a pretreatment of plasma samples with acetonitrile, chromatographic separations were efficiently achieved with a C18 column using a 9 min gradient system of 0.1% aqueous formic acid and acetonitrile as eluent. Drug candidate 5'-MeONB and chrysin (internal standard, IS) detection were carried out using ESI+ through the extracted ion chromatograms approach, monitored at m/z 433.1494 (for 5'-MeONB, tR:1.78 min) and m/z 255.0657 (for IS, tR:1.57 min). Method was validated according to US FDA guidelines, presenting linearity (R2 > 0.999) over concentration range of 30-750 ng/mL. Relative standard deviation (RSD) of repeatability and intermediary precision respectively ranged between 1.93-3.65% and 2.16-7.54%, considering lower limit of quantitation (30 ng/mL) and quality control (90, 360 and 600 ng/mL) samples, while accuracy was between 82.51 and 109.44%. Moreover, no interference from plasma endogenous substances, no carryover effect, and no influence of extraction method even in hemolyzed blood samples were observed. Sample stability in auto-sampler and long-term -80 °C storage, as well as matrix effect were within acceptable limits. For the first time, using the validated UPLC-MS bioanalytical method, the plasma pharmacokinetics of 5'-MeONB following 2 mg/kg intravenous bolus dosing to Wistar rats was characterized allowing the determination of the parameters describing drug distribution and elimination.
Assuntos
Anti-Inflamatórios/sangue , Cromatografia Líquida de Alta Pressão/métodos , Flavonas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Flavonas/química , Flavonas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
The natural isomers of resveratrol, cis- and trans-resveratrol, are natural phenolic substances synthetized via the shikimate pathway and found in many sources, including grapes, peanuts, blackberries, pistachios, cacao, cranberries, and jackfruits. They have functional and pharmacological properties such as anticarcinogenic, antidiabetic, anti-inflammatory, and cardioprotective activities. The aim of this article is to review the data published on resveratrol and its isomers, and their biosynthesis in plants, food sources, health and toxic effects, and the excretion of their metabolites. Due to its contribution to the promotion of human health, it is convenient to gather more knowledge about its functional properties, food sources, and the interactions with the human body during the processes of eating, digestion, absorption, biotransformation, and excretion, to combine this information to improve the understanding of these substances.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Fármacos Cardiovasculares/farmacologia , Alimentos , Hipoglicemiantes/farmacologia , Plantas/metabolismo , Resveratrol/farmacologia , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/toxicidade , Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/toxicidade , Disponibilidade Biológica , Biotransformação , Fármacos Cardiovasculares/metabolismo , Fármacos Cardiovasculares/farmacocinética , Fármacos Cardiovasculares/toxicidade , Vias de Eliminação de Fármacos , Absorção Gastrointestinal , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/toxicidade , Isomerismo , Resveratrol/metabolismo , Resveratrol/farmacocinética , Resveratrol/toxicidadeRESUMO
Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.
Assuntos
Monoterpenos Acíclicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fibromialgia/tratamento farmacológico , Nanocápsulas , Polímeros/administração & dosagem , Monoterpenos Acíclicos/farmacocinética , Monoterpenos Acíclicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula , SolubilidadeRESUMO
Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ2 followed by the formalin challenge. The nociceptive response was evaluated at different time-periods and the periarticular tissue and articular wash were collected for analysis. We found that intra-articular injection of PL-15d-PGJ2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ2. Moreover, a strong anti-inflammatory effect was observed with decreased levels of key pro-inflammatory cytokines and modulation of the leukocyte migration process. Our findings suggest that 15d-PGJ2 combined with a poloxamer micellar system provided clinical relevance in terms of bioavailability, long-lasting effect, and safe dosage. The formulation investigated herein is a promising micellar carrier system for managing pain conditions of the TMJ.
Assuntos
Anti-Inflamatórios/administração & dosagem , Artralgia/prevenção & controle , Portadores de Fármacos , Poloxâmero/química , Prostaglandina D2/análogos & derivados , Transtornos da Articulação Temporomandibular/prevenção & controle , Articulação Temporomandibular/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Artralgia/induzido quimicamente , Artralgia/metabolismo , Artralgia/fisiopatologia , Disponibilidade Biológica , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Formaldeído , Mediadores da Inflamação/metabolismo , Injeções Intra-Articulares , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Micelas , Prostaglandina D2/administração & dosagem , Prostaglandina D2/química , Prostaglandina D2/farmacocinética , Ratos Wistar , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/fisiopatologia , Distribuição TecidualRESUMO
The search for new drugs with anti-inflammatory properties remains a challenge for modern medicine. Among the various strategies for drug discovery, deriving new chemical entities from known bioactive natural and/or synthetic compounds remains a promising approach. Here, we designed and synthesized CVIB, a codrug developed by association of carvacrol (a phenolic monoterpene) with ibuprofen (a non-steroidal anti-inflammatory drug). In silico pharmacokinetic and physicochemical properties evaluation indicated low aqueous solubility (LogP ≥5.0). Nevertheless, the hybrid presented excellent oral bioavailability, gastrointestinal tract absorption, and low toxicity. CVIB did not present cytotoxicity in peripheral blood mononuclear cells (PBMCs), and promoted a significant reduction in IL-2, IL-10, IL-17, and IFN-γ cytokine levels in vitro. The LD50 was estimated to be approximately 5000â¯mg/kg. CVIB was stable and detectable in human plasma after 24â¯h. In vivo anti-inflammatory evaluations revealed that CVIB at 10 and 50â¯mg/kgâ¯i.p. caused a significant decrease in total leukocyte count (pâ¯<â¯0.01) and provoked a significant reduction in IL-1ß (pâ¯<â¯0.01). CVIB at 10â¯mg/kgâ¯i.p. efficiently decreased inflammatory parameters better than the physical mixture (carvacrol + ibuprofen 10â¯mg/kgâ¯i.p.). The results suggest that the codrug approach is a good option for drug design and development, creating the possibility of combining NSAIDs with natural products in order to obtain new hybrid drugs may be useful for treatment of inflammatory diseases.
Assuntos
Anti-Inflamatórios , Cimenos , Ibuprofeno , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Carragenina , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cimenos/química , Cimenos/farmacocinética , Cimenos/uso terapêutico , Cimenos/toxicidade , Citocinas/imunologia , Combinação de Medicamentos , Humanos , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/uso terapêutico , Ibuprofeno/toxicidade , Dose Letal Mediana , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Camundongos , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Pleurisia/imunologia , SolubilidadeRESUMO
Some recent studies have shown that pirfenidone (PFD) has favorable results in the healing process of the cornea. However, PFD in solution exhibits short half-life after topical application, and in this context, a liquid crystal nanoparticle system containing PFD (PFD-LCNPs) was developed. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, small angle X-ray diffraction and polarized light microscopy. The PFD-LCNPs had particle size and zeta potential of 247.3â¯nm and -33.60â¯mV (stores at 4⯰C), respectively, and 257.5â¯nm and -46.00â¯mV (stored at 25⯰C), respectively. The pH of the formulation was 6.9 and the encapsulation efficiency was 35.9%. The in vitro release profiles indicated that PFD sustained release from PFD-LCNPs for up to 12â¯h. In vitro study of ocular irritation (HET-CAM test) concluded that components of the formulation are well tolerated for ocular administration. Corneal re-epithelialization time after chemical burning was significantly reduced in rabbits treated with PFD-loaded LCNPs when compared to the group treated with a vehicle. In addition, the anti-inflammatory action of pirfenidone was observed by reducing myeloperoxidase activity (MPO) and inflammatory cells in the histology of the tissues of animals treated with PFD-LCNPs. These findings indicated that the PFD-LCNPs might have the potential for effective ocular drug delivery.
Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Queimaduras Químicas/tratamento farmacológico , Queimaduras Oculares/tratamento farmacológico , Cristais Líquidos , Nanopartículas/administração & dosagem , Piridonas/administração & dosagem , Administração Oftálmica , Analgésicos/farmacocinética , Animais , Anti-Inflamatórios/farmacocinética , Queimaduras Químicas/metabolismo , Queimaduras Químicas/patologia , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Córnea/efeitos dos fármacos , Córnea/metabolismo , Córnea/patologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/metabolismo , Queimaduras Oculares/patologia , Feminino , Tamanho da Partícula , Peroxidase/metabolismo , Piridonas/farmacocinética , CoelhosRESUMO
Multiple sclerosis (MS) is an autoimmune and neuroinflammatory disease characterized by demyelination of the Central Nervous System. Immune cells activation and release of pro-inflammatory cytokines play a crucial role in the disease modulation, decisively contributing to the neurodegeneration observed in MS and the experimental autoimmune encephalomyelitis (EAE), the widely used MS animal model. Synthetic glucocorticoids, commonly used to treat the MS attacks, have controversial effects on neuroinflammation and cognition. We sought to verify the influence of dexamethasone (DEX) on the EAE progression and on EAE-induced cognitive deficits. In myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced EAE female mice, treated once with DEX (50 mg/kg) or not, on the day of immunization, DEX decreased EAE-induced motor clinical scores, infiltrating cells in the spinal cord and delayed serum corticosterone peak. At the asymptomatic phase (8-day post-immunization), DEX did not protected from the EAE-induced memory consolidation deficits, which were accompanied by increased glucocorticoid receptor (GR) activity and decreased EGR-1 expression in the hippocampus. Blunting hippocampal GR genomic activation with DnGR vectors prevented DEX effects on EAE-induced memory impairment. These data suggest that, although DEX improves clinical signs, it decreases cognitive and memory capacity by diminishing neuronal activity and potentiating some aspects of neuroinflammation in EAE.
Assuntos
Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/tratamento farmacológico , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos Motores/etiologia , Transtornos Motores/prevenção & controle , Animais , Anti-Inflamatórios/farmacocinética , Corticosterona/sangue , Dexametasona/farmacocinética , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/diagnóstico , Imunofluorescência , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Motores/fisiopatologia , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Receptores de Glucocorticoides/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
Morin is a flavonoid has been reported with several pharmacological effects such as, antioxidant, anti-inflammatory, anticancer, antidiabetic, etc. However, morin has low solubility in water, which decreases the bioavailability and limits its clinical application. In this way, to improve the pharmaceutical properties, morin was complexed in hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and its oral bioavailability and anti-inflammatory effects were evaluated. Initially, a phase solubility study was performed, which showed that HP-ß-CD would be the better cyclodextrin for the formation of complexes with morin. The morin/HP-ß-CD inclusion complex (1:1) was prepared by freeze-drying method. The sample obtained was characterized by DSC, FTIR, PXRD, SEM and 1H NMR techniques, evidencing the formation of morin/HP-ß-CD inclusion complex. In addition, complexation efficiency (98.3%) and loading content (17.63%), determined by HPLC demonstrated that morin was efficiently complexed in HP-ß-CD. In vitro dissolution study confirmed that morin/HP-ß-CD inclusion complex increased the solubility and dissolution rate of morin. The oral bioavailability of the morin/HP-ß-CD complex and free morin were evaluated through a pharmacokinetic study in rat plasma. The oral bioavailability of morin complexed with HP-ß-CD was increased by 4.20 times compared with the free morin. Hyperalgesia induced by carrageenan and carrageenan-induced pleurisy were carried out in mice to evaluate the antihyperalgesic and anti-inflammatory activities of free morin and inclusion complex. Morin/HP-ß-CD inclusion complex showed antihyperalgesic effect in inflammatory pain model and anti-inflammatory effect decreasing leukocyte migration and TNF-α levels at a lower dose than free morin. Therefore, the morin/HP-ß-CD inclusion complex improved the solubility, dissolution rate, oral bioavailability, antihyperalgesic and anti-inflammatory effects of morin. In this way, the morin/HP-ß-CD inclusion complex exhibits potential for development of new pharmaceutical product for future clinical applications.