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1.
J Biomed Nanotechnol ; 17(8): 1612-1626, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544538

RESUMO

Nanotechnology is drawing attention nowadays due to its ability to regulate metals into nanosize, ultimately changing metal's physical, chemical, and optical properties. Silver nanoparticles are known for their potential impact as antimicrobial agents due to their inherent property penetrating the cell wall. The present study aimed to develop and statistically optimise using a novel combination of capsaicin loaded silver nanoparticles (AgCNPs) as an effective anti-bacterial agent to treat psoriasis using a green approach. Ascorbic acid was used as a reducing agent to fabricate silver nanoparticles. The formulation parameters optimisation was conducted using Box-Behnken Design (3×3 factorial design). The loading of capsaicin was confirmed by attenuated total reflectance-fourier transform infrared spectroscopy. Energy-dispersive X-ray spectroscopy-scanning electron microscopy (EDX-SEM) confirmed the existence of silver; net-like structure revealed in SEM and high-resolution transmission electron microscopy further confirmed the nano size of the formulation. Differential scanning calorimetry and X-ray diffraction demonstrated the capsaicin transformed into amorphous after encapsulated. An in-vitro microbial study showed that the 0.10 M formulation of AgCNPs exerted potent anti-bacterial activity, which can be considered an alternative anti-bacterial agent. It also displayed that the zone of inhibition was significantly high in gram-negative bacteria (E. coli) than gram-positive bacteria (S. aureus). Green synthesised AgCNPs showed highly significant anti-bacterial activity, which indicates that this formulation can be very promising for treating psoriasis.


Assuntos
Nanopartículas Metálicas , Prata , Capsaicina/farmacologia , Escherichia coli , Humanos , Staphylococcus aureus
2.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445392

RESUMO

Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells' suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.


Assuntos
Antígenos de Bactérias/efeitos adversos , Capsaicina/farmacologia , Neoplasias Bucais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipopolissacarídeos/efeitos adversos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/microbiologia , Ácidos Teicoicos/efeitos adversos
3.
Biomolecules ; 11(8)2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34439832

RESUMO

Two histamine receptor subtypes (HR), namely H1R and H4R, are involved in the transmission of histamine-induced itch as key components. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. The aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo as well as via Ca2+ imaging of murine sensory dorsal root ganglia (DRG) neurons in vitro. TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch, whereas TRPA1 inhibition reduced H4R- but not H1R-induced itch. TRPV1 and TRPA1 inhibition resulted in a reduced Ca2+ influx into sensory neurons in vitro. In conclusion, these results indicate that both channels, TRPV1 and TRPA1, are involved in the transmission of histamine-induced pruritus.


Assuntos
Cálcio/metabolismo , Gânglios Espinais/metabolismo , Prurido/genética , Células Receptoras Sensoriais/metabolismo , Canal de Cátion TRPA1/genética , Canais de Cátion TRPV/genética , Acetanilidas/farmacologia , Animais , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Feminino , Gânglios Espinais/efeitos dos fármacos , Expressão Gênica , Histamina/administração & dosagem , Masculino , Metilistaminas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Imagem Molecular , Cultura Primária de Células , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Prurido/metabolismo , Purinas/farmacologia , Rutênio Vermelho/farmacologia , Células Receptoras Sensoriais/efeitos dos fármacos , Transdução de Sinais , Canal de Cátion TRPA1/antagonistas & inibidores , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
4.
J Nutr Sci Vitaminol (Tokyo) ; 67(3): 196-200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193679

RESUMO

Taste is a chemical sensation that primarily detects nutrients present in food, and maintenance of taste sensations is important for ensuring that older people have a balanced nutritional diet. While several reports have suggested that taste sensitivity changes with age, the molecular mechanisms underlying this phenomenon are still unclear. Previous studies on the matter have focused mainly on the relationship between aging and taste detection of specific basic taste-inducing substances, and other than for these basic substances, understanding of how aging affects the detection of taste is limited. Therefore, to understand the effect that aging has on the taste detection of some familiar substances found in our daily meals, namely capsaicin and catechin, we investigated age-related changes in taste preferences to capsaicin and catechin in young and old C57BL/6J mice using a 48-h two-bottle preference test. For the capsaicin stimuli, the mice showed avoidance behavior in a concentration-dependent manner. However, we observed that there was no significant difference in the preference ratio for capsaicin between young and old mice. For the catechin stimuli, although both age groups showed avoidance behavior in a concentration-dependent manner, the preference ratio in old mice showed significantly higher values than those in young mice. This suggests that catechin sensitivity is declined due to aging. Thus, we observed that catechin sensitivity decreases with age, but capsaicin sensitivity does not.


Assuntos
Catequina , Paladar , Envelhecimento , Animais , Capsaicina/farmacologia , Preferências Alimentares , Camundongos , Camundongos Endogâmicos C57BL
5.
Life Sci ; 283: 119842, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34298038

RESUMO

AIMS: Ischemic stroke occurs when there is a sudden blockage of cerebral blood flow. This condition is a major cause of mortality, especially in low-income countries, and its incidence is dramatically increasing. Therapeutic strategies against stroke are therefore required. The present study explored the effects of dihydrocapsaicin on neuronal loss, brain infarct volume, and antioxidants in a rat model of permanent occlusion of the right middle cerebral artery (Rt.MCAO). MAIN METHODS: Male Wistar rats received dihydrocapsaicin intraperitoneally for 7 days after permanent occlusion of their right middle cerebral artery (Rt.MCAO). Then, the brain infarct volume, neuronal density, and antioxidant and anti-apoptotic activities in the cortex and hippocampus were determined at the end of the study. KEY FINDING: Dihydrocapsaicin treatment was found to significantly improve neuronal density, decrease infarct volume, reduce MDA elevation, improve CAT and SOD activities, decrease the density ratio of Bax and caspase-3, and increase the density ratio of Bcl-XL to ß-actin in the cerebral cortex and hippocampus. SIGNIFICANCE: The present study suggests that dihydrocapsaicin effectively mitigates cerebral ischemia-induced pathological changes in vivo, partly via antioxidant and anti-apoptotic pathways.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Isquemia Encefálica , Capsaicina/análogos & derivados , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Capsaicina/farmacologia , Caspase 3/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Wistar , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
6.
Cell Physiol Biochem ; 55(4): 428-448, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34242501

RESUMO

BACKGROUND/AIMS: Nociceptors detect noxious capsaicin (CAPS) via the transient receptor potential vanilloid 1 (TRPV1) ion channel, but coding mechanisms for relaying CAPS concentration [CAPS] remain obscure. Prolonged (up to 1h.) exposure to CAPS is used clinically to desensitise sensory fibres for treatment of neuropathic pain, but its signalling has typically been studied in cultures of dissociated sensory neurons employing low cell numbers and very short exposure times. Thus, it was pertinent to examine responses to longer CAPS exposures in large populations of adult neurons. METHODS: Confocal fluorescence microscopy was used to monitor the simultaneous excitation by CAPS of neuronal populations in intact L3/4 dorsal root ganglia (DRG) explants from adult pirt-GCaMP3 mice that express a cytoplasmic, genetically-encoded Ca2+ sensor in almost all primary sensory neurons. Peak analysis was performed using GraphPad Prism 9 to deconstruct the heterogenous and complex fluorescence signals observed into informative, readily-comparable measurements: number of signals, their lag time, maximum intensity relative to baseline (Max.) and duration. RESULTS: Exposure for 5 min. to CAPS activated plasmalemmal TRPV1 and led to increased fluorescence due to Ca2+ entry into DRG neurons (DRGNs), as it was prevented by capsazepine or removal of extracellular Ca2+. Increasing [CAPS] (0.3, 1 and 10 µM, respectively) evoked signals from more neurons (123, 275 and 390 from 5 DRG) with shorter average lag (6.4 ± 0.4, 3.3 ± 0.2 and 1.9 ± 0.1 min.) and longer duration (1.4 ± 0.2, 2.9 ± 0.2 and 4.8 ± 0.3 min.). Whilst raising [CAPS] produced a modest augmentation of Max. for individual neurons, those with large increases were selectively expedited; this contributed to a faster onset and higher peak of cumulative fluorescence for an enlarged responding neuronal population. CAPS caused many cells to fluctuate between high and low levels of fluorescence, with consecutive pulses increasing Max. and duration especially when exposure was extended from 5 to 20 min. Such signal facilitation counteracted tachyphylaxis, observed upon repeated exposure to 1 µM CAPS, preserving the cumulative fluorescence over time (signal density) in the population. CONCLUSION: Individual neurons within DRG differed extensively in the dynamics of response to CAPS, but systematic changes elicited by elevating [CAPS] increased signal density in a graded manner, unveiling a possible mechanism for population coding of responses to noxious chemicals. Signal density is sustained during prolonged and repeated exposure to CAPS, despite profound tachyphylaxis in some neurons, by signal facilitation in others. This may explain the burning sensation that persists for several hours when CAPS is used clinically.


Assuntos
Cálcio/metabolismo , Capsaicina/farmacologia , Gânglios Espinais/metabolismo , Nociceptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Animais , Feminino , Gânglios Espinais/citologia , Masculino , Camundongos , Camundongos Transgênicos , Nociceptores/citologia , Transdução de Sinais/genética , Canais de Cátion TRPV/genética
7.
J Int Soc Sports Nutr ; 18(1): 50, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154603

RESUMO

BACKGROUND: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men. METHODS: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). RESULTS: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05). CONCLUSION: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.


Assuntos
Capsaicina/análogos & derivados , Mediadores da Inflamação/sangue , Força Muscular/efeitos dos fármacos , Treinamento de Força/métodos , Adulto , Desempenho Atlético , Composição Corporal/efeitos dos fármacos , Água Corporal/efeitos dos fármacos , Água Corporal/metabolismo , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Método Duplo-Cego , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
8.
J Food Sci ; 86(7): 3195-3204, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34146398

RESUMO

Effect of capsaicinoids in hot pepper powder (HP) contains various chemical compounds, including capsaicin and dihydrocapsaicin, which are the main ingredients of the spicy taste. To evaluate the effect of HP on the microbial community in kimchi fermentation, kimchi [kimchi-HP, kimchi-HPE and kimchi-HPER made by adding HP, HP alcohol extract (HPE) and HPE residues (HPER)] was fermented at 4°C for 28 days. The pH and titratable acidity of the samples and the number of bacteria changed with fermentation time. Kimchi-HPER had significantly higher total viable and lactic acid bacteria (LAB) than other samples after 28 days of fermentation. The capsaicinoids content did not differ before and after fermentation, whereas the major free sugar content decreased, and the mannitol content increased. The principal component analysis (PCA) biplots showed similar patterns between kimchi-HP and -HPE. It was confirmed that Leuconostoc and Weissella were related to the initial fermentation, and Lactobacillus was involved in late fermentation. Kimchi-HP and kimchi-HPE increased the ratio of Lactobacillus sakei and decreased that of Leuconostoc mesenteroides compared to kimchi-HPER. Overall, these results revealed that capsaicinoids contained in HP affected Lactobacillus proliferation and mannitol increase during kimchi fermentation.


Assuntos
Bactérias/efeitos dos fármacos , Brassica rapa/microbiologia , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Capsicum/química , Alimentos e Bebidas Fermentados/análise , Açúcares/análise , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Fermentação , Microbiologia de Alimentos , Pós/química
9.
Exp Brain Res ; 239(8): 2375-2397, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34101000

RESUMO

A previous study has indicated that during the state of central sensitization induced by the intradermic injection of capsaicin, there is a gradual facilitation of the dorsal horn neuronal responses produced by stimulation of the high-threshold articular afferents that is counteracted by a concurrent increase of descending inhibitory actions. Since these changes occurred without significantly affecting the responses produced by stimulation of the low-threshold articular afferents, it was suggested that the capsaicin-induced descending inhibition included a preferential presynaptic modulation of the synaptic efficacy of the slow conducting nociceptive joint afferents (Ramírez-Morales et al., Exp Brain Res 237:1629-1641, 2019). The present study was aimed to investigate more directly the contribution of presynaptic mechanisms in this descending control. We found that in the barbiturate anesthetized cat, stimulation of the high-threshold myelinated afferents in the posterior articular nerve (PAN) produces primary afferent hyperpolarization (PAH) in the slow conducting (25-35 m/s) and primary afferent depolarization (PAD) in the fast conducting (40-50 m/s) articular fibers. During the state of central sensitization induced by capsaicin, there is a supraspinally mediated shift of the autogenic PAH to PAD that takes place in the slow conducting fibers, basically without affecting the autogenic PAD generated in the fast conducting afferents. It is suggested that the change of presynaptic facilitation to presynaptic inhibition induced by capsaicin on the slow articular afferents is part of an homeostatic process aimed to keep the nociceptive-induced neuronal activity within manageable limits while preserving the proprioceptive information required for proper control of movement.


Assuntos
Nociceptividade , Células do Corno Posterior , Animais , Capsaicina/farmacologia , Gatos , Estimulação Elétrica , Neurônios Aferentes , Nociceptores , Propriocepção , Medula Espinal
10.
Am J Physiol Renal Physiol ; 321(2): F195-F206, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34151591

RESUMO

The spontaneously hypertensive rat (SHR), a genetic model of high blood pressure, has also been studied as a potential model of overactive bladder. In vivo studies have confirmed the presence of surrogate markers of overactive bladder, including detrusor overactivity, increased urinary frequency, decreased bladder capacity and voided volume (VV), and afferent hypersensitivity to bladder irritation. However, these observations were during awake cystometry using implanted bladder catheters tethered to an infusion pump and artificially filled. We conducted experiments in awake unrestrained untethered age-matched female SHRs and Wistar rats to quantify naïve consumption and voiding behavior and the effect of capsaicin desensitization on consumption and voiding behavior. Food and water consumption, body weight, voiding frequency, and VV were recorded. Rats were placed in metabolism cages for 24 h, up to twice a week, from 17 to 37 wk of age. Compared with Wistar rats, SHRs exhibited decrease in VV and did not exhibit diurnal variation in VV between light and dark periods, suggesting that SHRs may have bladder hypersensitivity. Furthermore, SHRs may also have smaller bladder capacities, as they consumed less water, voided less volume (regardless of light cycle), and had equal urinary frequencies compared with age-matched Wistar rats. We detected no change in SHR voiding behavior following capsaicin desensitization, which was in contrast to a prior awake in vivo cystometry study describing increased VV and micturition interval in SHRs and suggests that C-fiber activity may not contribute to bladder hypersensitivity in SHRs.NEW & NOTEWORTHY We characterized the long-term (20 wk) voiding, defecation, and consumption behavior of age-matched spontaneously hypertensive and Wistar rats without the influence of anesthesia or catheters. Spontaneously hypertensive rats exhibited bladder hypersensitiviy that persisted for the 20-wk duration and was unaffected by capsacin desensitization.


Assuntos
Ritmo Circadiano/fisiologia , Hipertensão/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Micção/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Capsaicina/farmacologia , Ritmo Circadiano/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Micção/efeitos dos fármacos
11.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074030

RESUMO

The ability of organisms to quickly sense and transduce signals of environmental stresses is critical for their survival. Ca2+ is a versatile intracellular messenger involved in sensing a wide variety of stresses and regulating the subsequent cellular responses. So far, our understanding for calcium signaling was mostly obtained from ex vivo tissues and cultured cell lines, and the in vivo spatiotemporal dynamics of stress-triggered calcium signaling in a vertebrate remains to be characterized. Here, we describe the generation and characterization of a transgenic zebrafish line with ubiquitous expression of GCaMP6s, a genetically encoded calcium indicator (GECI). We developed a method to investigate the spatiotemporal patterns of Ca2+ events induced by heat stress. Exposure to heat stress elicited immediate and transient calcium signaling in developing zebrafish. Cells extensively distributed in the integument of the head and body trunk were the first batch of responders and different cell populations demonstrated distinct response patterns upon heat stress. Activity of the heat stress-induced calcium signaling peaked at 30 s and swiftly decreased to near the basal level at 120 s after the beginning of exposure. Inhibition of the heat-induced calcium signaling by LaCl3 and capsazepine and treatment with the inhibitors for CaMKII (Ca²2/calmodulin-dependent protein kinase II) and HSF1 (Heat shock factor 1) all significantly depressed the enhanced heat shock response (HSR). Together, we delineated the spatiotemporal dynamics of heat-induced calcium signaling and confirmed functions of the Ca2+-CaMKII-HSF1 pathway in regulating the HSR in zebrafish.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Calmodulina/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Resposta ao Choque Térmico/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Sinalização do Cálcio/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Calmodulina/genética , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Proteínas de Fluorescência Verde/genética , Fatores de Transcrição de Choque Térmico/antagonistas & inibidores , Fatores de Transcrição de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico/fisiologia , Hibridização In Situ , Lantânio/farmacologia , Microscopia de Fluorescência , Análise Espaço-Temporal , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/metabolismo
12.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066927

RESUMO

Anandamide (AEA) is one of the best characterized members of the endocannabinoid family and its involvement in many pathophysiological processes has been well documented in vertebrates and invertebrates. Here, we report the biochemical and functional characterization of key elements of the endocannabinoid system in hemocytes isolated from the Mediterranean mussel Mytilus galloprovincialis. We also show the effects of exogenous AEA, as well as of capsaicin, on the cell ability to migrate and to activate the respiratory burst, upon in vitro stimulation of phagocytosis. Interestingly, our findings show that both AEA and capsaicin suppress the hemocyte response and that the use of selective antagonists of CB2 and TRPV1 receptors revert their inhibitory effects. Overall, present data support previous evidence on the presence of endocannabinoid signaling in mollusks and advance our knowledge about the evolutionary origins of this endogenous system and its role in the innate response of mollusks.


Assuntos
Endocanabinoides/metabolismo , Mytilus/imunologia , Sequência de Aminoácidos , Animais , Ácidos Araquidônicos/farmacologia , Capsaicina/farmacologia , Endocanabinoides/farmacologia , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Mytilus/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Filogenia , Alcamidas Poli-Insaturadas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Canabinoides/química , Receptores de Canabinoides/genética , Receptores de Canabinoides/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
13.
J Biol Chem ; 297(1): 100806, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022223

RESUMO

Sensing noxiously high temperatures is crucial for living organisms to avoid heat-induced injury. The TRPV1 channel has long been known as a sensor for noxious heat. However, the mechanism of how this channel is activated by heat remains elusive. Here we found that a series of polyols including sucrose, sorbitol, and hyaluronan significantly elevate the heat activation threshold temperature of TRPV1. The modulatory effects of these polyols were only observed when they were perfused extracellularly. Interestingly, mutation of residues E601 and E649 in the outer pore region of TRPV1 largely abolished the effects of these polyols. We further observed that intraplantar injection of polyols into the hind paws of rats reduced their heat-induced pain response. Our observations not only suggest that the extracellular regions of TRPV1 are critical for the modulation of heat activation by polyols, but also indicate a potential role of polyols in reducing heat-induced pain sensation.


Assuntos
Temperatura Alta , Polímeros/farmacologia , Canais de Cátion TRPV/metabolismo , Sequência de Aminoácidos , Animais , Capsaicina/farmacologia , Espaço Extracelular/química , Feminino , Células HEK293 , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Polímeros/química , Prótons , Ratos Wistar , Canais de Cátion TRPV/química
14.
Biomolecules ; 11(3)2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804191

RESUMO

(1) Background: Capsaicin is the main capsaicinoid of the Capsicum genus and it is responsible for the pungent taste. Medical uses of the fruits of chili peppers date from the ancient time until nowadays. Most of all, they are used topically as analgesic in anti-inflammatory diseases as rheumatism, arthritis and in diabetic neuropathy. Reports state that the Capsicum genus, among other plant genera, is a good source of antimicrobial and antifungal compounds. The aim of this study was the preparation of a pharmaceutical Carbopol-based formulation containing capsaicin and the evaluation of its in vitro release and antimicrobial and antifungal properties. (2) Methods: It was first stabilized with an extraction method from the Capsicum annuum fruits with 98% ethanol and then the identification and determination of Capsaicin in this extract was realized by HPLC. (3) Results and Conclusions: Rheological analyses revealed that the selected formulation exhibited a pseudo-plastic behavior. In vitro release studies of capsaicin from a Carbopol-based formulation reported that approximately 50% of capsaicin was release within 52 h. Additionally, the Carbopol-based formulation significantly increased the antimicrobial effects of capsaicin towards all tested bacteria and fungi strains.


Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Resinas Acrílicas/química , Administração Tópica , Bactérias/efeitos dos fármacos , Etanol/química , Fungos/efeitos dos fármacos , Géis/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Viscosidade
15.
Biochem Biophys Res Commun ; 556: 156-162, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839411

RESUMO

The transient receptor potential vanilloid 1 (TRPV1) channel is a polymodal receptor in sensory nerves and involved in pain sensation. TRPV1 has at least three distinct activation modes that are selectively induced by different stimuli capsaicin, noxious heat, and protons. Although many mode-selective TRPV1 antagonists have been developed for their anticipated analgesic effects, there have been few successful reports because of adverse effects due to burn injuries and hyperthermia. Eugenol is a vanilloid that has been used as an analgesic in the dental treatment, and its TRPV1 activation ability has been reported. However, our knowledge about the underlying mechanisms of the antagonistic effects of eugenol on TRPV1 activation induced by three different modes is limited. Here, we show that eugenol dose-dependently inhibited the capsaicin-activated inward currents of mouse TRPV1 expressed in human embryonic kidney 293 (HEK293) cells. Under low pH conditions, low concentrations of eugenol only enhanced the proton-induced TRPV1 currents, whereas high eugenol concentrations initially potentiated but then immediately abrogated TRPV1 currents. Finally, eugenol had no modulatory effects on heat-activated TRPV1 in electrophysiological and Fura-2-based Ca2+ imaging experiments. Our results demonstrate that eugenol is a mode-selective antagonist of TRPV1 and can be evaluated as a lead compound of analgesics targeting TRPV1 without serious side effects.


Assuntos
Eugenol/farmacologia , Temperatura Alta , Prótons , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo , Animais , Ligação Competitiva/efeitos dos fármacos , Cálcio/metabolismo , Capsaicina/antagonistas & inibidores , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Condutividade Elétrica , Eugenol/administração & dosagem , Células HEK293 , Humanos , Camundongos
16.
ACS Appl Mater Interfaces ; 13(14): 16019-16035, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33819006

RESUMO

Recent research studies have shown that the low survival rate of liver cancer is due to drug resistance and metastasis. In the tumor microenvironment (TME), activated hepatic stellate cells (aHSCs) have been proven to favor the development of liver cancer. Hence, the combination therapy dual-targeting aHSCs and tumor cells might be an effective strategy for treatment of liver cancer. In this study, the novel multifunctional liposomes (CAPS-CUR/GA&Gal-Lip) were prepared for co-delivery of curcumin (CUR) and capsaicin (CAPS), in which glycyrrhetinic acid (GA) and galactose (Gal) were chosen as targeting ligands to modify the liposomes (Lip) for dual-targeting liver cancer. To mimic TME, a novel HSCs+HepG2 (human hepatoma cell line) cocultured model was established for the antitumor effect in vitro. The results showed that, compared to HepG2 cells alone, the cocultured model promoted drug resistance and migration by upregulating the expression of P-glycoprotein (P-gp) and Vimentin, which were effectively inhibited by CAPS-CUR/GA&Gal-Lip. The efficacy of the in vivo antitumor was evaluated by three mice models: subcutaneous H22 (mouse hepatoma cell line) tumor-bearing mice, H22+m-HSC (mouse hepatic stellate cell) tumor-bearing mice, and orthotopic H22 cells-bearing mice. The results showed that CAPS-CUR/GA&Gal-Lip exhibited lesser extracellular matrix (ECM) deposition, lesser tumor angiogenesis, and superior antitumor effect compared with the no- and/or Gal-modified Lip, which was attributed to the simultaneous blocking of the activation of HSCs and inhibition of the metastasis of tumor cells. The dual-targeting method using Lip is thus a potential strategy for liver cancer treatment.


Assuntos
Capsaicina/administração & dosagem , Curcumina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Lipossomos , Neoplasias Hepáticas Experimentais/prevenção & controle , Neoplasias Hepáticas/tratamento farmacológico , Metástase Neoplásica/prevenção & controle , Animais , Capsaicina/farmacologia , Curcumina/farmacologia , Feminino , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/patologia
17.
Biomolecules ; 11(4)2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920609

RESUMO

Spirulina platensis is a "super-food" and has attracted researchers' attention due to its anti-inflammatory, antioxidant, and analgesic properties. Herein, we investigated the antinociceptive effects of Spirulina in different rodent behavior models of inflammatory pain. Male Swiss mice were treated with Spirulina (3-300 mg/kg, p.o.), indomethacin (10 mg/kg, p.o.), or vehicle (0.9% NaCl 10 mL/kg). Behavioral tests were performed with administration of acetic acid (0.6%, i.p.), formalin 2.7% (formaldehyde 1%, i.pl.), menthol (1.2 µmol/paw, i.pl.), cinnamaldehyde (10 nmol/paw, i.pl.), capsaicin (1.6 µg/paw, i.pl.), glutamate (20 µmol/paw, i.pl.), or naloxone (1 mg/kg, i.p.). The animals were also exposed to the rotarod and open field test to determine possible effects of Spirulina on locomotion and motor coordination. The quantitative phytochemical assays exhibited that Spirulina contains significant concentrations of total phenols and flavonoid contents, as well as it showed a powerful antioxidant effect with the highest scavenging activity. Oral administration of Spirulina completely inhibited the abdominal contortions induced by acetic acid (ED50 = 20.51 mg/kg). Spirulina treatment showed significant inhibition of formalin-induced nociceptive behavior during the inflammatory phase, and the opioid-selective antagonist markedly blocked this effect. Furthermore, our data indicate that the mechanisms underlying Spirulina analgesia appear to be related to its ability to modulate TRMP8 and TRPA1, but not by TRPV1 or glutamatergic system. Spirulina represents an orally active and safe natural analgesic that exhibits great therapeutic potential for managing inflammatory pain disorders.


Assuntos
Analgésicos/farmacologia , Antagonistas de Entorpecentes/farmacologia , Dor Nociceptiva/tratamento farmacológico , Extratos Vegetais/farmacologia , Spirulina/química , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPM/metabolismo , Analgésicos/uso terapêutico , Animais , Capsaicina/farmacologia , Masculino , Camundongos , Naloxona/farmacologia , Nociceptividade/efeitos dos fármacos , Extratos Vegetais/uso terapêutico
18.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806052

RESUMO

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.


Assuntos
Canal de Cátion TRPA1/fisiologia , Canais de Cátion TRPV/fisiologia , Paladar , Animais , Peptídeo Relacionado com Gene de Calcitonina/química , Capsaicina/farmacologia , Cátions , Humanos , Camundongos , Neurônios/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Polimorfismo de Nucleotídeo Único , Ratos , República da Coreia , Células Receptoras Sensoriais/metabolismo , Especiarias , Substância P/metabolismo , Canal de Cátion TRPA1/química , Canais de Cátion TRPV/química , Papilas Gustativas/metabolismo , Nervo Trigêmeo/metabolismo
19.
Molecules ; 26(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800110

RESUMO

Chronic neuropathic pain, particularly peripheral pain, is a cause of great concern for diabetic patients. Current treatments include numerous agents such as capsaicinoids, a known deterrent of neuropathic pain despite the inconvenience associated with local side effects. In this context, the current work aims to elucidate the potential mechanisms involved in cytotoxicity by capsaicin and proposes an efficient formulation of capsaicin in alginate microcapsules, which significantly reduces side effects from capsaicin topical administration. For this, human dermal fibroblast cells were treated with alginate-microencapsulated capsaicin extracts and screened for potential cytotoxic effects produced by the treatment. Cell viability and morphology were examined, as well as oxidative stress status and anti-inflammatory potential. Our results show that the alginate encapsulated formulation of capsaicin exerted lower cytotoxic effects on human dermal fibroblasts as measured by cell viability and reactive oxygen species (ROS) production. Furthermore, the expression profiles of inflammatory cytokines were significantly altered by the treatment as compared with the control culture.


Assuntos
Alginatos/química , Capsaicina/administração & dosagem , Capsaicina/efeitos adversos , Cápsulas/administração & dosagem , Pele/efeitos dos fármacos , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Capsaicina/química , Capsaicina/farmacologia , Cápsulas/química , Cápsulas/farmacologia , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Pele/citologia
20.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806699

RESUMO

Nociceptors sense hazards via plasmalemmal cation channels, including transient receptor potential vanilloid 1 (TRPV1). Nerve growth factor (NGF) sensitises TRPV1 to capsaicin (CAPS), modulates nociceptor excitability and induces thermal hyperalgesia, but cellular mechanisms remain unclear. Confocal microscopy was used to image changes in intracellular Ca2+ concentration ([Ca2+]i) across neuronal populations in dorsal root ganglia (DRG) explants from pirt-GCaMP3 adult mice, which express a fluorescent reporter in their sensory neurons. Raised [Ca2+]i was detected in 84 neurons of three DRG explants exposed to NGF (100 ng/mL) and most (96%) of these were also excited by 1 µM CAPS. NGF elevated [Ca2+]i in about one-third of the neurons stimulated by 1 µM CAPS, whether applied before or after the latter. In neurons excitable by NGF, CAPS-evoked [Ca2+]i signals appeared significantly sooner (e.g., respective lags of 1.0 ± 0.1 and 1.9 ± 0.1 min), were much (>30%) brighter and lasted longer (6.6 ± 0.4 vs. 3.9 ± 0.2 min) relative to those non-responsive to the neurotrophin. CAPS tachyphylaxis lowered signal intensity by ~60% but was largely prevented by NGF. Increasing CAPS from 1 to 10 µM nearly doubled the number of cells activated but only modestly increased the amount co-activated by NGF. In conclusion, a sub-population of the CAPS-sensitive neurons in adult mouse DRG that can be excited by NGF is more sensitive to CAPS, responds with stronger signals and is further sensitised by transient exposure to the neurotrophin.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Capsaicina/farmacologia , Gânglios Espinais/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Neurônios/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Animais , Feminino , Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Masculino , Camundongos , Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Nociceptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo
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