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1.
J Ethnopharmacol ; 315: 116685, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37236382

RESUMO

ETHANOPHARMACOLOGICAL RELEVANCE: Acalypha indica Linn. is a weed, used traditionally for different skin diseases such as eczema and dermatitis in various parts of India. There are no previous in vivo studies reported on the antipsoriatic potential of this medicinal plant. AIM: The aim of this study was to investigate antipsoriatic activity of coconut oil dispersion of aerial portion of Acalypha indica Linn. Few lipid-soluble phytoconstituents of this plant were subjected to molecular docking studies on different targets to determine phytoconstituent responsible for antipsoriatic activity. METHODS: Virgin coconut oil dispersion of aerial portion of the plant was prepared by mixing three parts of coconut oil and one part of powdered aerial portion. The acute dermal toxicity was determined according to OECD guidelines. Mouse tail model was used to evaluate the antipsoriatic activity. Molecular docking of phytoconstituents was carried out using Biovia Discovery Studio. RESULTS: In acute dermal toxicity study,the coconut oil dispersion was found to be safe up to the dose of 20000 mg/kg. The dispersion exhibited significant antipsoriatic activity (p < 0.01) at the dose of 250 mg/kg; at 500 mg/kg dose, the activity was similar that of 250 mg/kg dose. In the docking study of the phytoconstituents, 2-methyl anthraquinone was found to be responsible for antipsoriatic activity. CONCLUSION: This study provides new evidence of Acalypha indica Linn as antipsoriatic plant and justifies its traditional use. Computational studies also endorse the results obtained via acute dermal toxicity study and mouse tail model for evaluation of antipsoriatic potential.


Assuntos
Acalypha , Fármacos Dermatológicos , Psoríase , Camundongos , Animais , Roedores , Óleo de Coco , Simulação de Acoplamento Molecular , Psoríase/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Fármacos Dermatológicos/farmacologia
2.
J Basic Clin Physiol Pharmacol ; 34(5): 603-615, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34161695

RESUMO

OBJECTIVES: Vascular dementia (VaD), being strongly associated with metabolic conditions is a major health concern around the world. Diabetes is a major risk factor for the development of VaD. This study investigates the efficacy of quercetin and folacin in diabetes induced vascular endothelium dysfunction and related dementia. METHODS: Single dose streptozotocin (STZ) (50 mg/kg i.p) was administered to albino Wistar rats (male, 200-250 g) by dissolving in citrate buffer. Morris water maze (MWM) and attentional set shifting tests were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), mitochondrial enzyme complex (I, II, and IV), inflammatory markers (interleukin-IL-6, IL-10, tumor necrosis factor-TNF-α, and myeloperoxidase-MPO), and acetylcholinesterase activity-AChE were also assessed. Quercetin (30 mg kg-1/60 mg kg-1) and folacin (30 mg kg-1/60 mg kg-1) were used as the treatment drugs. Donepezil (0.5 mg kg-1) was used as a positive control. RESULTS: STZ administered rats showed reduction in learning, memory, reversal learning, executive functioning, impairment in endothelial function, increase in brains' oxidative stress; inflammation; AChE activity, and decrease in mitochondrial complex (I, II, and IV) activity. Administration of quercetin and folacin in two different doses, significantly attenuated the STZ induced diabetes induced impairments in the behavioral, endothelial, and biochemical parameters. CONCLUSIONS: STZ administration caused diabetes and VaD which was attenuated by the administration of quercetin and folacin. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced VaD conditions.

3.
Recent Pat Nanotechnol ; 17(1): 15-17, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34303337

RESUMO

BACKGROUND: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. METHODS: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. RESULTS: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/subunit protein vaccines, peptide vaccines, virus-like particles, etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into patent clinical trials. CONCLUSION: Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Patentes como Assunto , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Sintéticas
4.
Dermatol Ther ; 35(11): e15830, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36106409

RESUMO

Skin disease treatment is a complex and time-consuming process due to the complex etiology, numerous side effects of conventional therapies, and difficulties in determining primary causes of the disease. Superficial wounds are often easy to treat. However, treatment of severe wounds caused by burn is challenging for clinicians. Optimum therapeutic benefits are based on the site-specific delivery of medicaments at the right time for a prolonged duration. Systemic toxicity and frequent dosing are the major challenges associated with the use of conventional therapeutics. Hydrogels are material of choice for drug delivery because of their high biocompatibility and ability to hold and release therapeutic agents. The number of hydrogels available for use in cosmetology and dermatology continues to grow during the past 1-2 decades. However, new hydrogel materials with high biocompatibility, antibacterial properties, and the ability to stimulate skin regeneration processes are in high demand. These are three-dimensional networks, which absorb a large amount of biological fluids and water. Hydrogels can be used as a biosensor, carrier systems for cells, drug delivery carriers especially for topical applications and in contact lenses. Hydrogels are highly porous carriers containing about 90% water. Stimuli-responsive hydrogels cause a change in network structure that is completely reversible in nature. The present review describes the applications of hydrogels in pharmaceutical formulations with a special emphasis on the treatment of dermatologic conditions such as acne, psoriasis, and mycosis.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Composição de Medicamentos , Antibacterianos/uso terapêutico , Água
5.
Acta Neurobiol Exp (Wars) ; 82(1): 35-51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35451422

RESUMO

Hyperserotonemia, during the early developmental phase, generates behavioral and biochemical phenotypes associated with autism spectrum disorder (ASD) in rats. Phosphodiesterase­1 (PDE1) inhibitors are known to provide benefits in various brain conditions. We investigated the role of a selective PDE1 inhibitor, vinpocetine on ASD­related behavioral phenotypes (social behavioral deficits, repetitive behavior, anxiety, and hyperlocomotion) in a developmental hyperserotonemia (DHS) rat model. Also, effects on biochemical markers related with neuronal function brain derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (pCREB), inflammation interleukins (IL­6 and IL­10) and tumor necrosis factor-alpha (TNF­α), and oxidative stress (TBARS and GSH) were studied in important brain areas (frontal cortex, cerebellum, hippocampus, and striatum). Administration of 5­methoxytryptamine (5­MT) to rats prenatally (gestational day 12) and in early developmental stages postnatal day (PND 0 - PND 20), resulted in impaired behavior and brain biochemistry. Administration of vinpocetine daily (10 and 20 mg/kg) to 5­MT rats from PND 21 to PND 48 resulted in an improvement of behavioral deficits. Also, vinpocetine administration significantly increased the levels of BDNF, ratio of pCREB/ CREB, IL­10, and GSH, and significantly decreased TNF­α, IL­6, and TBARS levels in different brain areas. Finally, our correlation analysis indicated that behavioral outcomes were significantly associated with the biochemical outcome. Vinpocetine, a selective PDE1 inhibitor, rectified important behavioral phenotypes related with ASD, possibly by improving markers of neuronal function, brain inflammation, and brain oxidative stress. Thus, PDE1 could be a potential target for pharmacological interventions and furthering our understanding of ASD pathogenesis.


Assuntos
Transtorno do Espectro Autista , Animais , Biomarcadores , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Inflamação/tratamento farmacológico , Interleucina-10/efeitos adversos , Interleucina-6 , Estresse Oxidativo , Inibidores de Fosfodiesterase/efeitos adversos , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico , Fator de Necrose Tumoral alfa/efeitos adversos , Alcaloides de Vinca
6.
Int J Mol Sci ; 23(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35269998

RESUMO

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70-80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Nanomedicina/métodos
7.
Autism Res ; 14(11): 2270-2286, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34415116

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal-valproic acid (pre-VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-α) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre-VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre-VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB/CREB, IL-10, and GSH along with significant decrease in TNF-α, IL-6, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre-VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD. LAY SUMMARY: ASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens-up a new line of enquiry for ASD treatment.


Assuntos
Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Animais , Comportamento Animal , Biomarcadores , Modelos Animais de Doenças , Proteína Duplacortina , Feminino , Inflamação , Estresse Oxidativo , Gravidez , Ratos , Ratos Wistar , Ácido Valproico , Alcaloides de Vinca
8.
J Pharm Pharmacol ; 73(11): 1460-1469, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34459916

RESUMO

OBJECTIVES: Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder, presenting with a variety of aetiological and phenotypical features. Inhibiting the enzyme phosphodiesterase-3 (PDE3) with cilostazol is known to produce beneficial effects in several brain disorders. The pharmacological outcome of cilostazol administration was investigated in prenatal valproic acid (VPA)-induced ASD deficits in albino Wistar rats. METHODS: Cilostazol was administered in two doses (30/60 mg/kg) to male rats born of females administered with VPA on gestational day 12. Behavioural assays on locomotion (open field), social interaction, repetitive behaviour (y-maze) and anxiety (elevated plus maze) were performed in all groups. Further, biochemical assessments of markers associated with neuronal function (BDNF, pCREB), inflammation (TNF-α, IL-6, IL-10) and oxidative stress were carried out in frontal cortex, hippocampus, striatum and cerebellum. KEY FINDINGS: The cilostazol regimen, attenuated prenatal VPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety. Further, biochemical markers such as BDNF, pCREB, IL-10 and GSH were found to be significantly increased contrary to markers such as TNF-α, IL-6 and TBARS in the assessed brain regions. CONCLUSIONS: Cilostazol rectified core behavioural traits while producing significant changes to biochemistry in the brain, suggesting benefits of cilostazol administration in experimental models of ASD.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cilostazol/uso terapêutico , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Anticonvulsivantes/efeitos adversos , Ansiedade/prevenção & controle , Transtorno do Espectro Autista/induzido quimicamente , Biomarcadores/metabolismo , Encéfalo/metabolismo , Cilostazol/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/prevenção & controle , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Ratos Wistar , Comportamento Social , Ácido Valproico/efeitos adversos
9.
Front Chem ; 9: 573748, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307293

RESUMO

Hydrogels possess a unique three-dimensional, cross-linked network of polymers capable of absorbing large amounts of water and biological fluids without dissolving. Nanohydrogels (NGs) or nanogels are composed of diverse types of polymers of synthetic or natural origin. Their combination is bound by a chemical covalent bond or is physically cross-linked with non-covalent bonds like electrostatic interactions, hydrophobic interactions, and hydrogen bonding. Its remarkable ability to absorb water or other fluids is mainly attributed to hydrophilic groups like hydroxyl, amide, and sulphate, etc. Natural biomolecules such as protein- or peptide-based nanohydrogels are an important category of hydrogels which possess high biocompatibility and metabolic degradability. The preparation of protein nanohydrogels and the subsequent encapsulation process generally involve use of environment friendly solvents and can be fabricated using different proteins, such as fibroins, albumin, collagen, elastin, gelatin, and lipoprotein, etc. involving emulsion, electrospray, and desolvation methods to name a few. Nanohydrogels are excellent biomaterials with broad applications in the areas of regenerative medicine, tissue engineering, and drug delivery due to certain advantages like biodegradability, biocompatibility, tunable mechanical strength, molecular binding abilities, and customizable responses to certain stimuli like ionic concentration, pH, and temperature. The present review aims to provide an insightful analysis of protein/peptide nanohydrogels including their preparation, biophysiochemical aspects, and applications in diverse disciplines like in drug delivery, immunotherapy, intracellular delivery, nutraceutical delivery, cell adhesion, and wound dressing. Naturally occurring structural proteins that are being explored in protein nanohydrogels, along with their unique properties, are also discussed briefly. Further, the review also covers the advantages, limitations, overview of clinical potential, toxicity aspects, stability issues, and future perspectives of protein nanohydrogels.

10.
Front Chem ; 9: 580118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981670

RESUMO

Nanotechnology has made a great impact on the pharmaceutical, biotechnology, food, and cosmetics industries. More than 40% of the approved drugs are lipophilic and have poor solubility. This is the major rate-limiting step that influences the release profile and bioavailability of drugs. Several approaches have been reported to administer lipophilic drugs with improved solubility and bioavailability. Nanotechnology plays a crucial role in the targeted delivery of poorly soluble drugs. Nanotechnology-based drug delivery systems can be classified as solid lipid nanoparticulate drug delivery systems, emulsion-based nanodrug delivery systems, vesicular drug delivery systems, etc. Nanotechnology presents a new frontier in research and development to conquer the limitations coupled with the conventional drug delivery systems through the formation of specific functionalized particles. This review presents a bird's eye view on various aspects of lipid nanoparticles as carriers of bioactive molecules that is, synthesis, characterization, advantage, disadvantage, toxicity, and application in the medical field. Update on recent development in terms of patents and clinical trials of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) have also been discussed in this article.

11.
Clin Exp Pharmacol Physiol ; 48(4): 614-625, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33480092

RESUMO

Hyperserotonemia, in the early developmental phase, generates a variety of behavioural and biochemical phenotypes associated with autism spectrum disorder (ASD) in rats. Papaverine is known to provide benefits in various brain conditions. We investigated the role of a selective phosphodiesterase-10A (PDE10A) inhibitor, papaverine on ASD related behavioural phenotypes (social behaviour deficits, repetitive behaviour, anxiety and hyperlocomotion) in developmental hyperserotonemia (DHS) rat model. Also, effects on important biochemical markers related with neuronal function (brain-derived neurotrophic factor (BDNF)-neuronal survival and phosphorylated-cAMP response element binding protein (pCREB)-neuronal transcription factor), brain inflammation (interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α) and brain oxidative stress (TBARS and GSH) were studied in important brain areas (frontal cortex, cerebellum, hippocampus and striatum). Administration of a non-selective serotonin receptor agonist, such as 5-methoxytryptamine (5-MT) to rats prenatally (gestational day 12 - day of parturition) and during early stages (postnatal day (PND) 0 -PND20) of development, resulted in impaired behaviour and brain biochemistry. Administration of papaverine (15/30 mg/kg ip) to 5-MT administered rats from PND21 to PND48, resulted in improvement of behavioural deficits. Also, papaverine administration significantly increased the levels of BDNF, pCREB/CREB, IL-10, GSH and significantly decreased TNF-α, IL-6 and TBARS levels in different brain areas. Papaverine, in both doses rectified important behavioural phenotypes related with ASD, the higher dose (30 mg/kg ip) showed significantly greater improvement than 15 mg/kg ip, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE10A could be a probable target for pharmacological interventions and furthering our understanding of ASD pathogenesis.


Assuntos
Transtorno do Espectro Autista , Papaverina , Animais , Comportamento Animal/efeitos dos fármacos , Neurônios , Estresse Oxidativo/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Ratos
12.
Eur J Pharmacol ; 890: 173663, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33127361

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Phosphodiesterase-10A (PDE10A) inhibition has shown to provide benefits in various brain conditions. We investigated the role of a PDE10A inhibitor, papaverine on core phenotypes in prenatal-valproic acid (Pre-VPA) model of ASD. In order to identify probable mechanisms involved, the effects on several protein markers of neuronal function such as, neurogenesis-DCX, neuronal survival-BDNF, synaptic transmission-synapsin-IIa, neuronal transcription factor-pCREB, neuronal inflammation (IL-6, IL-10 and TNF-α) and neuronal oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, hippocampus and striatum. Pre-VPA induced impairments in social behaviour, presence of repetitive behaviour, hyper-locomotion, anxiety, and diminished nociception were studied in male Albino Wistar rats. Administration of papaverine to Pre-VPA animals resulted in improvements of social behaviour, corrected repetitive behaviour, anxiety, locomotor, and nociceptive changes. Also, papaverine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB, IL-10 and GSH along with significant decrease in TNF-α, IL-6 and TBARS in different brain areas of Pre-VPA group. Finally, high association between behavioural parameters and biochemical parameters was observed upon Pearson's correlation analysis. Papaverine, administration rectified core behavioural phenotype of ASD, possibly by altering protein markers associated with neuronal survival, neurogenesis, neuronal transcription factor, neuronal transmission, neuronal inflammation, and neuronal oxidative stress. Implicating PDE10A as a possible target for furthering our understanding of ASD phenotypes.


Assuntos
Transtorno do Espectro Autista/prevenção & controle , Papaverina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Interação Social/efeitos dos fármacos , Ácido Valproico/toxicidade , Animais , Anticonvulsivantes/toxicidade , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/psicologia , Relação Dose-Resposta a Droga , Proteína Duplacortina , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Papaverina/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Ratos Wistar
13.
Curr Drug Res Rev ; 13(1): 59-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32787770

RESUMO

BACKGROUND/OBJECTIVE: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. METHODS: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. RESULTS: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. CONCLUSION: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.


Assuntos
Asma/tratamento farmacológico , Camellia sinensis/química , Antagonistas de Leucotrienos/farmacologia , Extratos Vegetais/farmacologia , Animais , Antiasmáticos/isolamento & purificação , Antiasmáticos/farmacocinética , Antiasmáticos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Área Sob a Curva , Preparações de Ação Retardada , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Cobaias , Histamina/imunologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Antagonistas de Leucotrienos/isolamento & purificação , Antagonistas de Leucotrienos/farmacocinética , Masculino , Mastócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacocinética , Folhas de Planta
15.
Med Hypotheses ; 142: 109838, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32442677

RESUMO

Psoriasis is a chronic relapsing inflammatory and hyperproliferative skin disease affecting quality of life. It affects an estimated 8 million Americans and more than 125 million people worldwide. The estimated cost to treat psoriasis in USA is over 13 billion US dollars per year. Treatment of psoriasis may include topical steroid-sparing agent, topical corticosteroids, phototherapy or biologics. Tacrolimus has 10-fold greater immunosuppressive activity than the ciclosporin A which has been recommended for effective treatment of psoriasis. However, it has been widely investigated using conventional formulation approaches which limit its clinical outcomes. It has poor cutaneous bioavailability when administered topically using conventional delivery approach, thus it has poor efficacy against the psoriasis. Low aqueous solubility and high degradation of Tacrolimus make it difficult to formulate as a liquid preparation. Moreover, Tacrolimus has narrow therapeutic index and thus it is essential to prevent its possible toxic effects when a modified release dosage form is administered. The present hypothesis aims to put forward to incorporate Tacrolimus into a novel lipid based nanocarrier system, which would be further loaded into a hydrogel base and evaluated for its target specific topic delivery. Due to the structural similarity of the lipid nanocarriers and skin, these vesicles would target the skin tissues effectively and treat psoriasis with minimum or no side effects. Thus, the proposed formulation would be a considerable value addition to the current therapeutic approaches used for psoriasis management.


Assuntos
Psoríase , Tacrolimo , Administração Cutânea , Humanos , Imunossupressores/uso terapêutico , Lipossomos , Psoríase/tratamento farmacológico , Qualidade de Vida , Tacrolimo/uso terapêutico
16.
Recent Pat Drug Deliv Formul ; 13(3): 174-183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544718

RESUMO

Antibiotic resistance is becoming one of the major obstacles to treatment success in various pathological conditions. Development process of a new antimicrobial agent is slow and difficult, whereas bacterial resistance is decreasing the arsenal of existing antibiotics. Therefore, there is a need to develop novel antibiotic formulations to combat the resistance of existing antibiotics. Nanoparticles are investigated as novel antibiotic formulation, but are often inefficient in practical applications. Nanotechnology presents a new frontier to overcome the issue of antibiotic resistance through the development of functionalized particles. Balance of physicochemical characteristics such as small particle size and high drug loading capacity along with improved stability are the challenges associated with large scale manufacturing of nanoantibiotic formulations. In the last 1-2 decades, a gradual increase in patents on nanoantibiotic formulations has been noted to address the resistance issues of antibiotic. The aim of this review is to consolidate recently-investigated nanoantibiotic formulations to combat antibiotic resistance.


Assuntos
Antibacterianos/administração & dosagem , Nanopartículas , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Nanotecnologia , Tamanho da Partícula , Patentes como Assunto
17.
Curr Alzheimer Res ; 16(13): 1216-1229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481003

RESUMO

Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on ß-amyloid plaques and tau pathology in Alzheimer's disease.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Glicoproteínas de Membrana/metabolismo , Emaranhados Neurofibrilares/metabolismo , Receptores Imunológicos/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , Emaranhados Neurofibrilares/patologia
18.
Cent Nerv Syst Agents Med Chem ; 19(3): 154-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31429696

RESUMO

Berberine (a protoberberine isoquinoline alkaloid) has shown promising pharmacological activities, including analgesic, anti-inflammatory, anticancer, antidiabetic, anti-hyperlipidemic, cardioprotective, memory enhancement, antidepressant, antioxidant, anti-nociceptive, antimicrobial, anti- HIV and cholesterol-lowering effects. It is used in the treatment of the neurodegenerative disorder. It has strong evidence to serve as a potent phytoconstituent in the treatment of various neurodegenerative disorders such as AD. It limits the extracellular amyloid plaques and intracellular neurofibrillary tangles. It has also lipid-glucose lowering ability, hence can be used as a protective agent in atherosclerosis and AD. However, more detailed investigations along with safety assessment of berberine are warranted to clarify its role in limiting various risk factors and AD-related pathologies. This review highlights the pharmacological basis to control oxidative stress, neuroinflammation and protective effect of berberine in AD, which will benefit to the biological scientists in understanding and exploring the new vistas of berberine in combating Alzheimer's disease.


Assuntos
Alcaloides/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Berberina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Alcaloides/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Berberina/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia
19.
Interv Med Appl Sci ; 11(1): 38-54, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32148902

RESUMO

Since the development of first lipid-based nanocarrier system, about 15% of the present pharmaceutical market uses nanomedicines to achieve medical benefits. Nanotechnology is an advanced area to meliorate the delivery of compounds for improved medical diagnosis and curing disease. Nanomedicines are gaining significant interest due to the ultra small size and large surface area to mass ratio. In this review, we discuss the potential of nanotechnology in delivering of active moieties for the disease therapy including their toxicity evidences. This communication will help the formulation scientists in understanding and exploring the new aspects of nanotechnology in the field of nanomedicine.

20.
Recent Pat Drug Deliv Formul ; 12(4): 267-276, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30539707

RESUMO

AIM AND BACKGROUND: The rationale of this study is that, treatment of asthmatic Guinea pig with combined administration of Montelukast sodium and Green Tea Extract (GTE) as a single capsule will mitigate the inflammatory injury in the airways and weaken the asthmatic response. Recent patents for the treatment of asthma researched a polyphenolic alternatives for antiasthmatic combination therapy, especially for those patients who remains unresponsive or poorly responsive for current asthma therapy (US7232585B2). Synergistic activity of green tea polyphenols and therapeutic, prophylatic agents are also reported in some recent patents (US20120172423A1, US20150320696A1). The present work is therefore aimed, to study the effect of Montelukast Sodium capsules coformulated with GTE on oxidative stress markers including Malondialdehyde (MDA), Glutathione (GSH) in different organs and Oxygen Radical Absorbance Capacity (ORAC) assay in plasma. MATERIALS AND METHODS: Guinea pigs were placed in histamine chamber and exposed to an aerosol challenge of 0.2% w/v histamine dihydrochloride in distilled water using pressurized air driven nebulizer at a pressure of 0.05 MPa-0.106 MPa for one week. After that, they were divided in to four groups of three each; control, asthmatic control, asthmatic treated with marketed preparation and asthmatic received developed capsules. After oral administration of formulations for three days, pigs were scarificed and oxidative stress markers level including cytoarchitectural manifestation in tissues was studied. RESULTS: In comparison with the healthy control group, MDA level of the asthmatic animal liver and lung was found to be elevated as 0.059 ± 0.031(p < 0.002) and 0.802 ± 0.310 (p < 0.005) respectively, whereas GSH level was declined as 13.223 ± 1.485 (p < 0.0001) in liver and 3.037 ± 0.282 (p < 0.0004) in lung tissues. TAC of asthmatic animal plasma was low as 2.132 ± 0.986 mM Trolox Eq/L (p < 0.009). The level of these biomarkers reverts back towards normal after treatment with marketed and developed formulation, although treatment with developed formulation was more efficacious since it was coformulated with GTE, which acts as an adjuvant for the management of inflammatory disease like asthma. CONCLUSION: It is contemplated that, use of GTE as an adjuvant to anti leukotriene drug played a significant role in asthma management by reducing oxidant injury. Since, studies in animals do not directly translate to human biology, further multi-control studies with better sampled patient population and more number of patients are needed.


Assuntos
Acetatos/uso terapêutico , Asma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Quinolinas/uso terapêutico , Chá/química , Acetatos/administração & dosagem , Administração Oral , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Asma/induzido quimicamente , Doença Crônica/tratamento farmacológico , Ciclopropanos , Combinação de Medicamentos , Feminino , Glutationa/metabolismo , Cobaias , Histamina , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Malondialdeído/metabolismo , Capacidade de Absorbância de Radicais de Oxigênio , Patentes como Assunto , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Quinolinas/administração & dosagem , Sulfetos
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