RESUMO
One of the essential organs and protective barricades, the skin, needs to be taken care of early. Skin is affected by several intrinsic and extrinsic factors, and despite their morphological and pathological differences, they have many molecular similarities. As of today, various mechanisms and theories have been recommended for aging, such as cellular anility, reduced proliferative tendency, reduction in length of telomere, mutations in DNA, theory of free radical generation, and many others. In today's society, skin health is often considered an important indicator of health, which has led to an increased demand for anti-aging products. However, numerous conventional cosmetics and phytocompounds (curcumin, Vitamin E, resveratrol) utilized in anti-aging products have inimical physical and chemical attributes, including insufficient chemical stability and inadequate skin penetration bound their effectuality after topical administration. So recently, new novel nanotechnological approaches for preventing skin aging, such as liposomes, niosomes, solid lipid nanoparticles, transferosomes, ethosomes, nanostructured lipid carriers, and carbon nanotubes, are being used. Hence, the field of cosmeceutical nanomaterials is rapidly evolving, and we can look forward to seeing a variety of innovative nanotechnology-based cosmetic products be a game-changer for this multi-million anti-aging cosmetic industry.
Assuntos
Cosméticos , Nanopartículas , Nanotubos de Carbono , Envelhecimento da Pele , Cosméticos/farmacologia , Cosméticos/uso terapêutico , Humanos , Lipossomos , Nanotecnologia , Pele/metabolismoRESUMO
Zika virus was declared a national emergency by WHO (World Health Organization) in 2016 when its widespread outbreaks and life-threatening complications were reported, especially in newborns and adults. Numerous studies reported that neuroinflammation is one of the significant root-causes behind its major neurological complications like microcephaly and Guillain-Barré syndrome (GBS). In this hypothesis, we propose Transient Receptor Potential Vanilloid 1 channel (TRPV1) as a major culprit in triggering positive inflammatory loop, ultimately leading to sustained neuroinflammation, one of the key clinical findings in Zika induced microcephalic and GBS patients. Opening of TRPV1 channel also leads to calcium influx and oxidative stress that ultimately results in cellular apoptosis (like Schwann cell in GBS and developing fetal nerve cells in microcephaly), ultimately leading to these complications. Currently, no specific cure exists for these complications. Most of the antiviral candidates are under clinical trials. Though there is no direct research on TRPV1 as a cause of Zika virus's neurological complications, but similarity in mechanisms is undeniable. Thus, exploring pathobiological involvement of TRPV1 channels and various TRPV1 modulators in these complications can possibly prove to be an effective futuristic therapeutic strategy for treatment and management of these life-threatening complications.
Assuntos
Microcefalia , Doenças do Sistema Nervoso , Infecção por Zika virus , Zika virus , Cálcio/metabolismo , Capsaicina , Humanos , Recém-Nascido , Doenças do Sistema Nervoso/tratamento farmacológico , Neurônios/metabolismo , Canais de Cátion TRPV , Zika virus/metabolismo , Infecção por Zika virus/complicações , Infecção por Zika virus/tratamento farmacológicoRESUMO
Atypical antipsychotics (AAPs) have the tendency of inducing severe metabolic alterations like obesity, diabetes mellitus, insulin resistance, dyslipidemia and cardiovascular complications. These alterations have been attributed to altered hypothalamic appetite regulation, energy sensing, insulin/leptin signaling, inflammatory reactions and active reward anticipation. Line of evidence suggests that transient receptor potential vanilloid type 1 and 3 (TRPV1 and TRPV3) channels are emerging targets in treatment of obesity, diabetes mellitus and could modulate feed intake. The present study was aimed to investigate the putative role TRPV1/TRPV3 in olanzapine-induced metabolic alterations in mice. Female BALB/c mice were treated with olanzapine for six weeks to induce metabolic alterations. Non-selective TRPV1/TRPV3 antagonist (ruthenium red) and selective TRPV1 (capsazepine) and TRPV3 antagonists (2,2-diphenyltetrahydrofuran or DPTHF) were used to investigate the involvement of TRPV1/TRPV3 in chronic olanzapine-induced metabolic alterations. These metabolic alterations were differentially reversed by ruthenium red and capsazepine, while DPTHF didn't show any significant effect. Olanzapine treatment also altered the mRNA expression of hypothalamic appetite-regulating and nutrient-sensing factors, inflammatory genes and TRPV1/TRPV3, which were reversed with ruthenium red and capsazepine treatment. Furthermore, olanzapine treatment also increased expression of TRPV1/TRPV3 in nucleus accumbens (NAc), TRPV3 expression in ventral tegmental area (VTA), which were reversed by the respective antagonists. However, DPTHF treatment showed reduced feed intake in olanzapine treated mice, which might be due to TRPV3 specific antagonism and reduced hedonic feed intake. In conclusion, our results suggested the putative role TRPV1 in hypothalamic dysregulations and TRPV3 in the mesolimbic pathway; both regulate feeding in olanzapine treated mice.
Assuntos
Regulação do Apetite/efeitos dos fármacos , Inflamação/metabolismo , Olanzapina/farmacologia , Canais de Cátion TRPV/metabolismo , Animais , Capsaicina/administração & dosagem , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Corantes/administração & dosagem , Corantes/farmacologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Furanos/administração & dosagem , Furanos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Teste de Tolerância a Glucose , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Hipotálamo/efeitos dos fármacos , Inflamação/genética , Metformina/administração & dosagem , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Atividade Motora , Rutênio Vermelho/administração & dosagem , Rutênio Vermelho/farmacologia , Fármacos do Sistema Sensorial/administração & dosagem , Fármacos do Sistema Sensorial/farmacologia , Canais de Cátion TRPV/genéticaRESUMO
The present research work was designed to examine the neuroprotective effect of ethanolic extract of Solanum virginianum Linn. (SV) in chronic construction injury (CCI) of sciatic nerve-induced neuropathic pain in rats. The extract was initially standardized by high-performance thin-layer chromatography using solasodine as a biomarker and was then subjected to assess the degree of mechanical allodynia, thermal allodynia, mechanical hyperalgesia, thermal hyperalgesia and biochemical evaluations. Administration of SV (100 and 200 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) as a reference standard significantly debilitated hyperalgesia and allodynia and notably restored the altered antioxidant level and pro-inflammatory cytokine (IL-1ß and TNF-α) expression in a dose-dependent manner. Further, to appraise the mechanistic approach of solasodine, docking simulation studies were done on the 3D structure of the voltage-gated N-type calcium channel (Cav 2.2), R-type calcium channel (Cav 2.3) and sodium channel (Nav 1.7), and the results revealed that solasodine properly positioned into Phe 19, Leu 32, Met 51 and Met 71 (FLMM pocket) of Cav 2.2 and Cav 2.3 and being a competitor of Ca2+/N-lobe it may inactivate these calcium channels but did not bind into the desired binding pocket of Nav 1.7. Thus, the study confirmed the role of solasodine as a major biomarker for the observed neuroprotective nature of Solanum virginianum.
Assuntos
Analgésicos/farmacologia , Hiperalgesia/prevenção & controle , Simulação de Acoplamento Molecular , Neuralgia/prevenção & controle , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neuropatia Ciática/tratamento farmacológico , Alcaloides de Solanáceas/farmacologia , Solanum , Analgésicos/isolamento & purificação , Analgésicos/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Sítios de Ligação , Ligação Competitiva , Canais de Cálcio Tipo N/efeitos dos fármacos , Canais de Cálcio Tipo N/metabolismo , Modelos Animais de Doenças , Etanol/química , Feminino , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Ligação Proteica , Ratos Wistar , Neuropatia Ciática/metabolismo , Neuropatia Ciática/fisiopatologia , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/metabolismo , Solanum/química , Solventes/químicaRESUMO
Diabetes mellitus is a serious debilitating epidemic affecting all social strata, imposing huge health, social and economic burdens. Diabetic neuropathic pain, an important microvascular complication of diabetes mellitus, characterized by allodynia and hyperalgesia, is recognized as one of the most difficult types of pain to treat. The development of tolerance, inadequate relief and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. Reactive oxygen/nitrogen species, cytokines and matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diabetic neuropathy. The present study was designed to explore the effect of naringenin, a citrus flavonoid, on streptozotocin induced diabetic neuropathic pain in Wistar rats. After 8 weeks of diabetes induction, rats developed neuropathy which was evident from marked hyperalgesia and allodynia associated with enhanced oxidative-nitrosative stress, release of inflammatory mediators (TNF-α, TGF-1ß), MMP-9 activation and decreased motor nerve conduction velocity. Treatment with naringenin (25, 50, 100 mg kg-1) for 4 weeks starting from the 5th week of streptozotocin injection significantly attenuated behavioral, biochemical and molecular changes, along with alterations in motor nerve conduction velocity in a dose-dependent manner. Moreover, diabetic rats treated with insulin-naringenin combination produced a more pronounced effect as compared to individual drugs. The major finding of the study is that insulin alone corrected the hyperglycemia and partially reversed the pain response in diabetic rats. However, combination with naringenin not only attenuated the diabetic condition but also reversed neuropathic pain through modulation of oxidative-nitrosative stress, inflammatory cytokine release and MMP inhibition in the diabetic rats. Modulation of MMP-9 by a natural flavonoid like naringenin seems to be a novel approach to target diabetic neuropathic pain.
Assuntos
Analgésicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Flavanonas/uso terapêutico , Neuralgia/tratamento farmacológico , Analgésicos/administração & dosagem , Animais , Citocinas/metabolismo , Diabetes Mellitus Experimental , Relação Dose-Resposta a Droga , Flavanonas/administração & dosagem , Metaloproteinase 9 da Matriz/metabolismo , Estresse Oxidativo , Medição da Dor , Fitoterapia , Distribuição Aleatória , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with symptoms ranging from lack of social interaction and communication deficits to rigid, repetitive, and stereotypic behavior. It has also been associated with comorbidities such as anxiety, aggression, epilepsy, deficit in sensory processing, as well as ADHD (attention deficit hyperactivity disorder). Apart from several behavioral and cognitive complications arising as a result of central nervous system dysfunction, there are various physiological comorbidities such as immune system deregulation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and gastrointestinal complications which can worsen existing behavioral complications. There are no available treatments for these physiological comorbidities. The prevalence of gastrointestinal complications in ASD ranges from 9% to 70% and it correlates with behaviors consistent with the autistic endophenotype indicating that these are one of the major comorbidities associated with ASD. A strong connection of gut-brain cross talk occurs as a result of gut dysbiosis responsible for excessive production of short-chain fatty acids such as propanoic acid (PPA) by abnormal gut flora in ASD patients. This worsens behavioral, neurochemical, and mitochondrial dysfunction occurring in ASD. These physiological comorbidities are responsible for the generation of free radical species that cause immune system dysfunction leading to synthesis of various pro-inflammatory cytokines and chemokines. This in turn causes activation of microglia. Dietary phytochemicals are thought to be safer and useful as an alternative neurotherapeutic moiety. These compounds provide neuroprotection by modulating signaling pathways such as Nrf2, NF-κB, MAPK pathway or Sirtuin-FoxO pathway. There has been recent evidence in scientific literature regarding the modulation of gut-brain cross talk responsible for behavioral, biochemical, and mitochondrial dysfunction as well as cellular and behavioral sensory alterations by dietary phytochemicals such as curcumin, resveratrol, naringenin, and sulforaphane. These dietary phytochemicals can be formulated in novel brain-targeted delivery systems which overcome their limitation of low oral bioavailability and short half-life leading to prolonged action. Till date, not much work has been done on the development of brain-targeted neurotherapeutics for ASD. In this chapter we discuss plausible mechanisms and evidence from our own and other scientific research for the utilization of curcumin, resveratrol, naringenin, and sulforaphane as neurotherapeutics for ASD.
Assuntos
Transtorno do Espectro Autista/dietoterapia , Transtorno do Espectro Autista/fisiopatologia , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/uso terapêutico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/fisiopatologia , HumanosRESUMO
Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.
Assuntos
Antipsicóticos/uso terapêutico , Berberina/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Olanzapina/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Antipsicóticos/efeitos adversos , Berberina/efeitos adversos , Temperatura Corporal , Peso Corporal , Citocinas/metabolismo , Ingestão de Líquidos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/sangue , Grelina/metabolismo , Hipotálamo/metabolismo , Leptina/sangue , Leptina/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Neuropeptídeos/metabolismo , Obesidade , RNA Mensageiro , Transdução de Sinais , Canais de Cátion TRPV/genética , Resultado do TratamentoRESUMO
AIM: Neuroinflammatory response triggered by the stimulation of matrix metalloproteinases plays a pivotal role in the development of autistic phenotype. MMPs stimulate inflammatory cytokines release along with mitochondrial deficits that ultimately lead to neuronal dysfunction and precipitate autistic symptoms. The aim of the present study was to explore the neuropsychopharmacotherapeutic efficacy of curcumin in the experimental paradigm of autism spectrum disorders. MATERIALS AND METHODS: 1M propanoic acid (4µl) was infused over 10min into the anterior portion of the caudoputamen to induce autistic behavior in rats. Curcumin (50, 100 and 200mg/kg) was administered per orally starting from 2nd day of surgery and continued up to 28th day. Rats were tested for various neurobehavioural paradigms like social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning and memory as well as for repetitive and pervasive behavior. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-α and MMP-9 were also carried out. KEY FINDINGS: Intracerebroventricular injection of propanoic acid produced neurological, sensory, behavioral, biochemical and molecular deficits which were assessed as endophenotype of autism spectrum disorders. Regular treatment with curcumin for four weeks significantly and dose dependently restored neurological, behavioral, biochemical and molecular changes associated with autistic phenotype in rats. SIGNIFICANCE: The major finding of the study is that curcumin restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-α and MMP-9 in PPA-induced autism in rats. Therefore, curcumin can be developed as a potential neuropsychopharmacotherapeutic adjunct for autism spectrum disorders (ASD).
Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Fármacos do Sistema Nervoso Central/uso terapêutico , Curcumina/uso terapêutico , Psicotrópicos/uso terapêutico , Animais , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/psicologia , Comportamento Animal/efeitos dos fármacos , Núcleo Caudado , Injeções Intraventriculares , Relações Interpessoais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Propionatos , Putamen , Ratos , Ratos Sprague-Dawley , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Chronic unpredictable stressors can produce a situation similar to clinical depression and such animal models can be used for the preclinical evaluation of antidepressants. Nitric oxide, a secondary messenger molecule, has been implicated in neurotransmission, synaptic plasticity, learning, aggression and depression. Vaccinium myrtillus (bilberry) extract is a potent inhibitor of reactive oxygen/nitrogen species and cytokine production. The present study investigated the role of nitric oxide in the antidepressant action of Vaccinium myrtillus in unpredictable chronic mild stress-induced depression in mice. Animals were subjected to different stress paradigms daily for a period of 21 days to induce depressive-like behavior. Pretreatment with L-arginine significantly reversed the protective effect of bilberry (500 mg/kg) on chronic stress-induced behavioral (immobility period, sucrose preference) and biochemical (lipid peroxidation and nitrite levels; endogenous antioxidant activities) in stressed mice. Furthermore, L-NAME (10 mg/kg) pretreatment with a sub-effective dose of bilberry (250 mg/kg) significantly potentiated the protective effect of bilberry extract. The study revealed that modulation of the nitric oxide pathway might be involved in antidepressant-like effects of Vaccinium myrtillus in stressed mice.
Assuntos
Antocianinas/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Estresse Fisiológico , Vaccinium myrtillus/química , Animais , Antocianinas/administração & dosagem , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Arginina/efeitos adversos , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos , Masculino , Camundongos , Atividade Motora , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Fitoterapia , Extratos Vegetais , Espécies Reativas de Oxigênio/metabolismoRESUMO
Small-fiber painful peripheral neuropathy is one of the long-term complications of alcohol for which there is no reliable successful therapy available. The precise mechanisms by which chronic alcohol consumption produces peripheral nerve fiber damage and loss remain unclear. Emerging data from clinical and preclinical studies suggest that increased oxidative-nitrodative stress mediated release of proinflammatory cytokines from damaged neural tissues may play a central role in the pathogenesis of alcoholic neuropathy. The present study investigated the effect of both the isoforms of vitamin E (α-tocopherol and tocotrienol) against chronic alcohol-induced peripheral neuropathy in rats. Ethanol treated rats showed a significant decrease in paw-withdrawal threshold in both Randall-Selitto and von-Frey hair tests along with a significant reduction in tail flick latency in the tail-immersion test. A decreased pain threshold was associated with significant alterations in oxidative-nitrodative stress markers and an increase in proinflammatory cytokines (TNF-α and IL-1ß). The 4-week treatment with tocotrienol significantly ameliorated behavioral, biochemical and molecular alterations in alcohol treated rats. However, α-tocopherol failed to produce any protective effect. The results of the present study suggest that oxidative-nitrodative stress mediated cytokine signaling may be responsible for alcohol-induced peripheral neurotoxicity and tocotrienol treatment might be beneficial in chronic alcoholics exhibiting neuropathy.
Assuntos
Neuropatia Alcoólica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Tocotrienóis/farmacologia , alfa-Tocoferol/farmacologia , Animais , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos , Masculino , Medição da Dor , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. Diabetic neuropathic pain is amongst the most difficult types of pain to treat mainly due to the lack of understanding of its etiology and inadequate relief with available drug therapy. The present study targeted oxidative stress mediated nerve damage in diabetic rats using an aqueous extract of Emblica officinalis, a potent natural antioxidant. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test (thermal hyperalgesia) and decreased paw withdrawal threshold in both Randall-Selitto (mechanical hyperalgesia) and von-Frey hair test (mechanical allodynia). A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress, nitrite levels and cytokines (TNF-α, IL-1ß and TGF-ß1) both in the serum and sciatic nerve of diabetic rats. Treatment with the Emblica officinalis aqueous extract (250, 500 and 1000 mg/kg/day) significantly attenuated all the behavioral, biochemical and molecular alterations in a dose-dependent manner. The major finding of the study is that insulin alone corrected the hyperglycemia and partially reversed the pain response in diabetic rats. However, combination with Emblica officinalis extract not only attenuated the diabetic condition but also reversed neuropathic pain through modulation of oxidative-nitrosative stress in diabetic rats.
Assuntos
Antioxidantes/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Neuralgia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Phyllanthus emblica , Fitoterapia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/metabolismo , Relação Dose-Resposta a Droga , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Neuralgia/etiologia , Neuralgia/metabolismo , Nitritos/metabolismo , Nitrosação/efeitos dos fármacos , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismoRESUMO
INTRODUCTION: Depression is one of the most prevalent and life-threatening forms of mental illness associated with significant disability and mortality. About 21% of the world's population is affected by depression. AREAS COVERED: The various pathological factors involved in depression are: monoamine hypothesis, neurotransmitter receptor hypothesis, neurotrophic factor hypothesis, hypothalamic-pituitary-adrenal (HPA) dysregulation, oxidative stress, cytokine hypothesis and NO pathway. Recent drug therapies used to treat depression include: selective serotonin re-uptake inhibitors, norepinephrine and dopamine re-uptake inhibitors and several herbal drugs. The present review focuses on recently unraveled pathogenetic hypotheses and therapeutics of mental depression. Moreover, various evaluation models for antidepressants are discussed. EXPERT OPINION: Stress can be considered as a major contributor to the development of depressive disorder due to the dysregulation of HPA axis. Cytokine effects on behavior are believed to be related in part to their effects on neurotransmitter and neuropeptide function, synaptic plasticity and neuroendocrine function. Although there are multiple pathways that are involved in the pathogenesis of depression, the current antidepressants mainly target monoaminergic pathway. However, the therapeutic potential of other pathways is still under investigation. Drugs targeting NO, cytokines and the kynurenine acid pathway might be the drugs of choice in near future.
Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Animais , Antidepressivos/efeitos adversos , Ensaios Clínicos como Assunto , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Cinurenina/metabolismo , Masculino , Terapia de Alvo Molecular , Óxido Nítrico/metabolismo , Transdução de SinaisRESUMO
Probiotics produce a beneficial impact on the host by improving the endogenous flora. It has been advocated that nonpathogenic bacteria like Lactobacillus and Bifidobacterium may undergo antagonistic interactions with other bacterial strains and can be used to control pathogenic bacteria. Novel modes of therapeutic and prophylactic interventions are based on their consumption either alone or in combination with prebiotics. Usefulness of probiotics has been implicated in allergies, cancer, AIDS, and respiratory and urinary tract infections. In this review we have listed various findings suggesting their benefits in alleviating symptoms associated with aging, fatigue, and autism. Newer claims indicating their role in reducing the risks of osteoporosis, obesity, and possibly type 2 diabetes are also discussed. Considering the wide array of such activities, the present review comprehensively elaborates upon the proposed benefits of probiotics. The concept of synbiotics, a combination of probiotics and prebiotics beneficially affecting the survival and implantation of such live organisms, is also discussed. Available probiotic strains, their commercial preparations, and newer approaches to improve the efficacy and overcome limitations of the therapy are also discussed in relation to the future of probiotic therapy. Considering that the purported claims about disease risk reduction are tentative, the review also encompasses various aspects regarding the safety of probiotics and their possible future role in disease prevention.
Assuntos
Enteropatias/terapia , Probióticos/uso terapêutico , Infecções Bacterianas/terapia , Bifidobacterium , Humanos , Lactobacillus , Probióticos/efeitos adversosRESUMO
Curcumin is a yellow-colored plant polyphenol with a long history of medicinal use in ayurvedic, Chinese and Japanese medicine. Studies have reported the cyclooxygenase COX-2-inhibitory activity of this polyphenol; however, none of the studies have established its antiinflammatory activity in the rat cotton pellet granuloma pouch model, which mimics subchronic inflammation in humans. The present study was conducted to evaluate the effect of curcumin in the cotton pellet granuloma pouch model. Furthermore, the interaction of curcumin with standard anti-inflammatory drugs at subeffective doses was studied to evaluate its potential role as adjuvant therapy. Administration of curcumin (240 mg/kg i.p.), aspirin (160 mg/kg i.p.) or rofecoxib (5 mg/kg i.p.) for 6 days in the cotton pellet granuloma pouch test exhibited significant anti-inflammatory activity, as demonstrated by a decrease in both dry and wet weights of the cotton pellet as compared to the control animals. Lower doses of curcumin (120 mg/kg i.p.), aspirin (80 mg/kg i.p.) or rofecoxib (2.5 mg/kg i.p.) were ineffective. However, the combination of a subeffective dose of curcumin (120 mg/kg i.p.) with submaximal doses of aspirin (80 mg/kg i.p.) or rofecoxib (2.5 mg/kg i.p.) produced a synergistic effect. Furthermore, there was marked increase in tumor necrosis factor-alpha (TNF-alpha) levels (estimated by enzyme-linked immunosorbent assay, ELISA) in the serum of the animals implanted with cotton pellets presenting marked inflammatory events. Daily administration of curcumin, aspirin or rofecoxib decreased the levels of TNF-alpha, further demonstrating anti-inflammatory activity. Curcumin in combination with aspirin or rofecoxib caused a further decrease in serum TNF-alpha levels. In conclusion, the results of the present study demonstrate an anti-inflammatory effect for curcumin in the cotton pellet granuloma pouch test, possibly acting through COX enzyme inhibition, and further inhibiting the generation of inflammatory mediators such as TNF-alpha. These results point toward the usefulness of curcumin as adjuvant drug therapy along with standard anti-inflammatory drugs.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Granuloma/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Aspirina/farmacologia , Curcumina/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Ensaio de Imunoadsorção Enzimática , Lactonas/administração & dosagem , Lactonas/farmacologia , Masculino , Medicina Tradicional , Ratos , Ratos Wistar , Sulfonas/administração & dosagem , Sulfonas/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Peripheral neuropathy is one of the common complications of diabetes mellitus. It is frequently associated with debilitating pain. The present study was designed to investigate effect of Lycopene, a carotenoid found in tomatoes, on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. After 4-weeks of STZ injection, diabetic mice exhibited a significant thermal hyperalgesia cold allodynia, hyperglycemia and loss of body weights as compared with control rats. Chronic treatment of lycopene for 4 weeks significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of antioxidant such as lycopene as an adjuvant therapy in the treatment of diabetic neuropathy.
Assuntos
Antioxidantes/farmacologia , Carotenoides/farmacologia , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Animais , Temperatura Baixa , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/tratamento farmacológico , Temperatura Alta , Licopeno , Masculino , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Diabetic neuropathic pain, an important microvascular complication of diabetes mellitus is recognized as one of the most difficult types of pain to treat. The development of tolerance, inadequate relief and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of lycopene and its effect on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) release in streptozotocin induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia alongwith increased plasma glucose and decreased body weights as compared with control mice. Lycopene (1, 2 and 4 mg/kg body weight; per oral) treatment, from the 4th to 8th week after streptozotocin injection, significantly attenuated thermal hyperalgesia and the hot-plate latencies. Lycopene also inhibited the TNF-alpha and NO release in a dose dependent manner. These results indicate an antinociceptive activity of lycopene possibly through its inhibitory action on NO and TNF-alpha release and point towards its potential to attenuate diabetic neuropathic pain.
Assuntos
Analgésicos não Narcóticos/uso terapêutico , Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Analgésicos não Narcóticos/farmacologia , Animais , Antioxidantes/farmacologia , Glicemia/análise , Carotenoides/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/etiologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Tolerância a Medicamentos , Temperatura Alta/efeitos adversos , Hiperalgesia/etiologia , Licopeno , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Animais , Óxido Nítrico/metabolismo , Estresse Oxidativo , Distribuição Aleatória , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Emerging epidemiological data indicates that diabetes is a potential predisposing factor for neuropsychiatric deficits as stroke, cerebrovascular diseases, diabetic encephalopathy, depression and anxiety. Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. Curcumin, a well-established phenolic antioxidant and anti-inflammatory molecule, is capable of playing an important role against amyloid and dendritic pathology and thus has neuroprotective properties. The aim of the present study was to explore the effect of curcumin (60 mg/kg; p.o.) on cognitive functions, oxidative stress and inflammation in diabetic rats. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 80% in the cerebral cortex of diabetic rats. There was 107% and 121% rise in thiobarbituric acid reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Reduced glutathione level and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in cerebral cortex and hippocampus were increased by 112% and 94% respectively. Serum TNF-alpha, a marker for inflammation, was found to increase by 1100% in diabetic rats. Chronic treatment with curcumin (60 mg/kg; p.o.) significantly attenuated cognitive deficit, cholinergic dysfunction, oxidative stress and inflammation in diabetic rats. The results emphasize the involvement of cholinergic dysfunction, oxidative stress and inflammation in the development of cognitive impairment in diabetic animals and point towards the potential of curcumin as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.
Assuntos
Encefalopatias Metabólicas/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Curcumina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encefalopatias Metabólicas/etiologia , Encefalopatias Metabólicas/fisiopatologia , Catalase/metabolismo , Córtex Cerebral/metabolismo , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Glutationa/metabolismo , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Nitritos/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that enhanced oxidative stress caused by oxygen-centered free radicals may contribute to the pathogenesis of cisplatin-induced acute renal failure. 6-Gingerol is claimed to be a potent antioxidant. The present study was performed to explore the renoprotective potential of 6-gingerol on cisplatin-induced oxidative stress and renal dysfunction. METHODS: 6-Gingerol in dosages of 12.5, 25, 50 mg/kg was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. RESULTS: A single dose of cisplatin resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. 6-Gingerol treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. CONCLUSIONS: The present study demonstrates the renoprotective potential of 6-gingerol against cisplatin-induced oxidative stress and renal dysfunction in rats. Hence, 6-gingerol has a potential to be used as therapeutic adjuvant in cisplatin nephrotoxicity.