RESUMO
Neurological disorders pose a huge worldwide challenge to the healthcare system, necessitating innovative strategies for targeted drug delivery to the central nervous system. Alzheimer's disease (AD) is an untreatable neurodegenerative condition characterized by dementia and alterations in a patient's physiological and mental states. Since ancient times, medicinal plants have been an important source of bioactive phytochemicals with immense therapeutic potential. This review investigates new and safer alternatives for prevention and treatment of disease related to inevitable side effects associated with synthetic compounds. This review examines how nanotechnology can help in enhancing the delivery of neuroprotective phytochemicals in AD. Nevertheless, despite their remarkable neuroprotective properties, these natural products often have poor therapeutic efficacy due to low bioavailability, limited solubility and imperfect blood brain barrier (BBB) penetration. Nanotechnology produces personalized drug delivery systems which are necessary for solving such problems. In overcoming these challenges, nanotechnology might be employed as a way forward whereby customized medication delivery systems would be established as a result. The use of nanocarriers in the design and application of important phytochemicals is highlighted by this review, which indicate potential for revolutionizing neuroprotective drug delivery. We also explore the complications and possibilities of using nanocarriers to supply nutraceuticals and improve patients' standard of living, and preclinical as well as clinical investigations displaying that these techniques are effective in mitigating neurodegenerative diseases. In order to fight brain diseases and improve patient's health, scientists and doctors can employ nanotechnology with its possible therapeutic interventions.
Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Compostos Fitoquímicos , Humanos , Doença de Alzheimer/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/administração & dosagem , Animais , Nanopartículas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Nanotecnologia/métodos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismoRESUMO
This study aimed to investigate the effects of prenatal docosahexaenoic acid (DHA) supplementation on pregnancy outcomes through a systematic review and meta-analysis. We hypothesized that prenatal DHA intake through supplements will improve pregnancy outcomes. Detailed literature search was performed using online databases such as PubMed, EMBASE, and Google Scholar till November 2022, to identify the randomized controlled trials (RCT) with maternal intake of DHA supplementation during the latter half of pregnancy compared to the placebo/control. Based on the inclusion and exclusion criteria, nine RCTs involving 5710 subjects were included. This meta-analysis showed that DHA supplementation (450-800 mg/day) was associated with a significantly higher birth weight of infants (Inverse variance [IV]: 101.71 [57.36-146.06] at 95% CI, P = .00001, I2 = 0%), and fewer low birth weights (LBWs) (Mantel-Haenszel [M-H]: 0.53 [0.33-0.86] at 95% CI, P = .01, I2 = 72%), with lesser but statistically insignificant pre-term births (PTB) (M-H: -0.02 [-0.04 to 0.00] at 95% CI, P = .07, I2 = 0%) compared to the placebo. However, the DHA supplementation has no effect on gestational length (IV: -2.26 [-9.64 to 5.12] at 95% CI, P = .55, I2 = 100%) compared to the placebo. In conclusion, the outcomes of this meta-analysis showed that prenatal DHA supplementation (450-800 mg/day) may reduce the risk of preterm births and increase infant birth weight.
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Peso ao Nascer , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Resultado da Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Recém-Nascido de Baixo Peso , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Purpose: Proteins and peptides have secured a place as excellent therapeutic moieties on account of their high selectivity and efficacy. However due to oral absorption limitations, current formulations are mostly delivered parenterally. Oral delivery of peptides and proteins (PPs) can be considered the need of the hour due to the immense benefits of this route. This review aims to critically examine and summarize the innovations and mechanisms involved in oral delivery of peptide and protein drugs. Methods: Comprehensive literature search was undertaken, spanning the early development to the current state of the art, using online search tools (PubMed, Google Scholar, ScienceDirect and Scopus). Results: Research in oral delivery of proteins and peptides has a rich history and the development of biologics has encouraged additional research effort in recent decades. Enzyme hydrolysis and inadequate permeation into intestinal mucosa are the major causes that result in limited oral absorption of biologics. Pharmaceutical and technological strategies including use of absorption enhancers, enzyme inhibition, chemical modification (PEGylation, pro-drug approach, peptidomimetics, glycosylation), particulate delivery (polymeric nanoparticles, liposomes, micelles, microspheres), site-specific delivery in the gastrointestinal tract (GIT), membrane transporters, novel approaches (self-nanoemulsifying drug delivery systems, Eligen technology, Peptelligence, self-assembling bubble carrier approach, luminal unfolding microneedle injector, microneedles) and lymphatic targeting, are discussed. Limitations of these strategies and possible innovations for improving oral bioavailability of protein and peptide drugs are discussed. Conclusion: This review underlines the application of oral route for peptide and protein delivery, which can direct the formulation scientist for better exploitation of this route.
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Statin-associated diabetes (SAD) is an issue that has come to light after a series of recent clinical trials that has led to the issue of a black box warning for statins by the US FDA. However, the benefit of statin outweighs its risk. Nevertheless, experiments have been conducted to identify the mechanism by which statins aggravate the risk of diabetes only in a select population who bear the risk factors of obesity, sedentary lifestyle, hypertension, and other associated risk factors of lifestyle disorders. In this study, the possibility of utilization of a phyto-molecule, sesamol, for its ability to combat statin-associated diabetes using atorvastatin as the agent of choice has been explored. MMP assay and western blot was conducted to investigate the effects of atorvastatin on apoptotic cascade with sesamol as a protective agent was conducted in MIN-6 cells. Effect of the combination was tested in L6 cells with 2-NBDG uptake assay and as well as western blot for GLUT-4. A diet-induced hypercholesterolemia model was developed in an in vivo model animals and treated with atorvastatin and sesamol with histopathological analysis being carried out to evaluate the apoptotic markers and GLUT-4 presence. It was found that sesamol can combat pancreatic beta cell apoptosis via the internal apoptotic pathway activated by atorvastatin. With regards to muscle cells, sesamol could improve the GLUT-4 vesical production, but not improve glucose uptake which is inhibited by atorvastatin. These findings are further confirmed by animal studies. These findings indicate that sesamol can serve as a prototype molecule for further development and investigation of similar compounds to tackle SAD.
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Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.
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Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/terapia , Pé Diabético/diagnóstico , CicatrizaçãoRESUMO
The post-treatment status of breast cancer survivors has become a concern because of the toxicity induced by chemotherapeutic agents in the brain tissues resulting in cognitive deficits, which is generally referred as chemobrain. The aim of this study was to assess the effect of a proprietary ayurvedic formulation Mulmina Mango against chemotherapy-induced cognitive impairment (CICI). Mammary carcinoma was induced by subcutaneously inoculating 4T1 cells into the mammary fat pad of the animals. Intraperitoneal administration of Cyclophosphamide, Methotrexate, 5-Fluorouracil (CMF) regimen was carried out once a week for three weeks. Treatment of Mulmina began one week before chemotherapy and continued till the end of the chemotherapy cycle. After three cycles of chemotherapy, cognitive decline was assessed by Morris water maze task followed by assessment of locomotor activity by open-field test. Tumor progression was evaluated by measurement of tumor volume. Oxidative and neuroinflammatory markers were also evaluated from the isolated brain samples. CMF treatment resulted in a considerable reduction in tumour volume. We found chemotherapy negatively affected behavioral and biochemical parameters in animals and Mulmina treatment ameliorated these cognitive impairments by restoring antioxidant and maintaining cytokine levels. The combination of phytochemicals in Mulmina proved its possible ability to alleviate CICI without affecting chemotherapeutic efficiency and could pave the way for identifying treatment strategies to combat chemobrain.
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Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Mangifera/química , Ayurveda , Compostos Fitoquímicos/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/metabolismo , Disfunção Cognitiva/diagnóstico , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologiaRESUMO
[This corrects the article DOI: 10.3892/br.2020.1377.].
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BACKGROUND: Dementia is a neurodegenerative disorder majorly evidenced by cognitive impairment. Although there are many types of dementia, the common underlying etiological factors in all the types are neuro-inflammation or aging induced apoptosis. ß-caryophyllene, a cannabinoid type-2 receptor agonist, has been reported to have promising neuroprotective effects in cerebral ischemia and neuro-inflammation. OBJECTIVE: In the present study, we evaluated the effects of ß-caryophyllene against animal models of dementia whose etiology mimicked neuro-inflammation and aging. METHODS: Two doses (50 and 100 mg/kg of body weight) of ß-caryophyllene given orally were tested against AlCl3-induced dementia in male Sprague Dawley (SD) rats using the Morris water maze test. Subsequently, the effect of the drug was assessed for episodic memory in female SD rats using novel object recognition task in doxorubicin-induced neuro-inflammation and chemobrain model. Moreover, its effects were evaluated in D-galactose-induced mitochondrial dysfunction leading to dementia. RESULTS: ß-caryophyllene, at both doses, showed significant improvement in memory when assessed using parameters like target quadrant entries, escape latency and path efficiency in the Morris water maze test for spatial memory. In the doxorubicin-induced chemobrain model, ß-caryophyllene at 100 mg/kg significantly elevated acetylcholinesterase and catalase levels and lowered lipid peroxidation compared to the disease control. In the novel object recognition task, ß-caryophyllene at 100 mg/kg significantly improved recognition index and discrimination index in the treated animals compared to the disease control, with a significant increase in catalase and a decrease in lipid peroxidation in both hippocampus and frontal cortex. However, in the D-galactose-induced mitochondrial dysfunction model, ß-caryophyllene failed to show positive effects when spatial memory was assessed. It also failed to improve D-galactose-induced diminished mitochondrial complex I and II activities. CONCLUSION: Hence, we conclude that ß-caryophyllene at 100 mg/kg protects against dementia induced by neuro-inflammation with no effect on neuronal aging induced by mitochondrial dysfunction.
Assuntos
Envelhecimento/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Demência/metabolismo , Doenças Mitocondriais/metabolismo , Doenças Neuroinflamatórias/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Cloreto de Alumínio/metabolismo , Animais , Modelos Animais de Doenças , Galactose/metabolismo , Hipocampo/efeitos dos fármacos , Peroxidação de Lipídeos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The aim of the present study was to evaluate a marketed formulation against chemotherapy-induced cognitive dysfunction. The formulation, Mulmina™, contains natural compounds which are known to help in improving function as well as in preventing cognitive decline. All of the phytoconstituents in the formulation have been tested individually but this is the first study where such a formulation has been evaluated against chemotherapy-induced cognitive decline (CICD) in a mouse model. CICD was induced by cyclophosphamide (50 mg/kg), methotrexate (5 mg/kg), and 5-fluorouracil (5 mg/kg) (CMF), administered intraperitonially. CMF was administered in three cycles, with one injection per week for three weeks. The decline in cognition of the mice was evaluated by a test of locomotor activity (Open Field Test) followed by a test for spatial memory (Morris Water Maze). Biochemical parameters evaluated include brain cytokine levels and BDNF levels via ELISA. Hematological counts were also performed to evaluate any changes in blood profile using a veterinary blood cell counter. Levels of oxidative stress markers with respect to catalase activity and lipid peroxidation were also evaluated in the brain using UV-spectrophotometric analysis. Mulmina™ was able to show significant improvement in cognitive function post chemotherapy when compared to the untreated animals. Apart from improvement in spatial memory, there was also an improvement in biochemical parameters. The particular combination of phytochemicals in Mulmina™ proved themselves successful in alleviating the CICD in this preliminary study and pave a path for future studies which can establish the solid grounds with respect to molecular and pharmacological basis for the mechanism of action of Mulmina™.
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BACKGROUND: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition. METHODS: Sesamol-PLGA (SM-PLGA) nanosuspension was developed using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections. RESULTS: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed. CONCLUSION: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.
Assuntos
Benzodioxóis/uso terapêutico , Pé Diabético/tratamento farmacológico , Nanopartículas/química , Fenóis/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Cicatrização/efeitos dos fármacos , Animais , Benzodioxóis/sangue , Benzodioxóis/farmacocinética , Benzodioxóis/farmacologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Pé Diabético/sangue , Pé Diabético/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Liberação Controlada de Fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Teste de Tolerância a Glucose , Proteínas de Choque Térmico HSP27/metabolismo , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Fenóis/sangue , Fenóis/farmacocinética , Fenóis/farmacologia , Fator de Crescimento Derivado de Plaquetas , Álcool de Polivinil/química , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Estreptozocina/farmacologia , Suspensões , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.
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COVID-19 , Surtos de Doenças , Quarentena , COVID-19/epidemiologia , COVID-19/terapia , COVID-19/transmissão , China/epidemiologia , HumanosRESUMO
BACKGROUND: The aim of the study was to investigate the effects of morin on skin breaking strength, hydroxyproline, lysyl oxidase, DNA and RNA content of experimentally inflicted wounds in rats. METHODS: This study was performed on albino rats of either sex at the Central Animal Research Facility (CARF), Manipal University. RESULTS: Morin showed significant wound contraction on day 7 as compared to control with mean closure of 47.44±6.07% in excision wound model. Granulation tissue breaking strength was significantly increased (p<0.05) in the morin treated group with 180.2±7.94 g when compared to control at 151.2±6.99 g. There was a significant increase in hydroxyproline content with the morin treated group when compared to control with 3.41±0.33 µg/mg of granulation tissue. Similarly, the wound parameters were improved with the morin treated group in dexamethasone delayed healing. CONCLUSIONS: Our results suggest that morin treatment accelerates the healing process delayed by concurrent use of steroids.