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1.
Metabolites ; 13(10)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37887429

RESUMO

South Africa is rich in diverse medicinal plants, and it is reported to have over 35% of the global Helichrysum species, many of which are utilized in traditional medicine. Various phytochemical studies have offered valuable insights into the chemistry of Helichrysum plants, hinting at bioactive components that define the medicinal properties of the plant. However, there are still knowledge gaps regarding the size and diversity of the Helichrysum chemical space. As such, continuous efforts are needed to comprehensively characterize the phytochemistry of Helichrysum, which will subsequently contribute to the discovery and exploration of Helichrysum-derived natural products for drug discovery. Thus, reported herein is a computational metabolomics work to comprehensively characterize the metabolic landscape of the medicinal herb Helichrysum splendidum, which is less studied. Metabolites were methanol-extracted and analyzed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Spectral data were mined using molecular networking (MN) strategies. The results revealed that the metabolic map of H. splendidum is chemically diverse, with chemical superclasses that include organic polymers, benzenoids, lipid and lipid-like molecules, alkaloids, and derivatives, phenylpropanoids and polyketides. These results point to a vastly rich chemistry with potential bioactivities, and the latter was demonstrated through computationally assessing the binding of selected metabolites with CDK-2 and CCNB1 anti-cancer targets. Molecular docking results showed that flavonoids (luteolin, dihydroquercetin, and isorhamnetin) and terpenoids (tiliroside and silybin) interact strongly with the CDK-2 and CCNB1 targets. Thus, this work suggests that these flavonoid and terpenoid compounds from H. splendidum are potentially anti-cancer agents through their ability to interact with these proteins involved in cancer pathways and progression. As such, these actionable insights are a necessary step for further exploration and translational studies for H. splendidum-derived compounds for drug discovery.

2.
Am J Cancer Res ; 13(7): 2773-2789, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37559981

RESUMO

Cancer is one of the most common and widely diagnosed diseases worldwide. With an increase in prevalence and incidence, many studies in cancer biology have been looking at the role pro-cancer proteins play. One of these proteins is the Really Interesting New Gene (RING), which has been studied extensively due to its structure and functions such as apoptosis, neddylation, and its role in ubiquitination. The RING domain is a cysteine-rich domain known to bind Cysteine and Histidine residues. It also binds two zinc ions that help stabilize the protein in various patterns, often with a 'cross-brace' topology. Different RING finger proteins have been studied and found to have suitable targets for developing anti-cancer therapeutics. These identified candidate proteins include Parkin, COP1, MDM2, BARD1, BRCA-1, PIRH2, c-CBL, SIAH1, RBX1 and RNF8. Inhibiting these candidate proteins provides opportunities for shutting down pathways associated with tumour development and metastasis.

3.
Plants (Basel) ; 12(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36678982

RESUMO

Plants undergo metabolic perturbations under various abiotic stress conditions; due to their sessile nature, the metabolic network of plants requires continuous reconfigurations in response to environmental stimuli to maintain homeostasis and combat stress. The comprehensive analysis of these metabolic features will thus give an overview of plant metabolic responses and strategies applied to mitigate the deleterious effects of stress conditions at a biochemical level. In recent years, the adoption of metabolomics studies has gained significant attention due to the growing technological advances in analytical biochemistry (plant metabolomics). The complexity of the plant biochemical landscape requires sophisticated, advanced analytical methods. As such, technological advancements in the field of metabolomics have been realized, aided much by the development and refinement of separatory techniques, including liquid and gas chromatography (LC and GC), often hyphenated to state-of-the-art detection instruments such as mass spectrometry (MS) or nuclear resonance magnetic (NMR) spectroscopy. Significant advances and developments in these techniques are briefly highlighted in this review. The enormous progress made thus far also comes with the dawn of the Internet of Things (IoT) and technology housed in machine learning (ML)-based computational tools for data acquisition, mining, and analysis in the 4IR era allowing for broader metabolic coverage and biological interpretation of the cellular status of plants under varying environmental conditions. Thus, scientists can paint a holistic and comprehensive roadmap and predictive models for metabolite-guided crop improvement. The current review outlines the application of metabolomics and related technological advances in elucidating plant responses to abiotic stress, mainly focusing on heavy metal toxicity and subsequent osmotic stress tolerance.

4.
Toxicol Rep ; 9: 1920-1928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518449

RESUMO

Background: The focus on traditional and complementary medicine for supplementation and treatment of diseases is high. Aspalathus linearis commonly known as Rooibos showed several beneficial effects, this led to the standardized production of a pharmaceutical grade green rooibos extract (Afriplex TM GRT) with enhanced polyphenolic content. The aim of this study was to assess toxicity of Afriplex TM GRT in HepG2/C3A cells and Sprague Dawley rats. Methods: Afriplex GRT TM (0.1, 1, 10, 100, or 1000 µg/mL) in DMSO was added to the media to the final 0.01% DMSO for treatment of HepG2/C3A for 1, 24 and 48 hrs followed by MTT and ATP assays. Sprague Dawley rats were grouped to Control, Afriplex TM GRT treated (10, 100 and 300 mg/kg); and acute (24hrs tetrachloromethane (CCl 4) injected hepatotoxicity control). Serum biochemistry, histology and Western blot analysis on liver were performed. Results: Afriplex TM GRT significantly reduced cell viability at 100 and 1000µg/mL after 48 hrs. Acute CCl 4 treatment significantly increased serum alanine aminotransferase in rats. The highest extract treatment of 300 mg/kg significantly elevated aspartate amino transferase. There was severe macro vesicular in the CCl 4 group whereas mild to moderate micro vesicular steatosis was seen in the 300 mg/kg Afriplex TM GRT treated group. Highest extract treatment significantly reduced NFkB expression on Western blot analysis. Conclusion: The beneficial effects of pharmaceutical grade Afriplex GRT TM are concentration and dosage based. Afriplex GRT TM exerts its beneficial effects via NFkB as demonstrated by the dose dependent reduction of NFkB on Western blot analysis. More work need to be done to explore the exact mechanism that occurs in the NFkB pathway.

5.
Am J Transl Res ; 14(9): 6150-6162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247303

RESUMO

BACKGROUND: Targeting protein-protein interactions (PPIs) linked to protein quality control (PQC) pathways as potential anti-cancer drug targets have unanimously widened biological insights and the therapeutic potential of PPIs as smart-drug discovery tools in cancer. PPIs between disease-relevant proteins associated with protein homeostasis in PQC pathways have been linked to improved mechanistic understanding associated with conformational abnormalities and impairment, cellular proteotoxicity, induced apoptosis, and pathogenesis in different types of cancers. In this context, PPIs between small nuclear ribonucleoprotein polypeptide G (SNRPG) and heat shock protein 70.14 (Hsp70.14) have attracted attention as potential smart drug discovery tools in cancer diagnostics and therapeutics. Validated evidence of high-quality biological data has shown the presence of the two proteins in different types of cancers including breast cancer. The links between SNRPG and Hsp70.14 in cancer-cell networks remain elusive, overlooked, and uncharacterized. METHODOLOGY: In this study, we explored the interaction between the two oncogenic proteins using the MST-based assays. RESULTS: The results revealed a low KD in the nanomolar concentration range of 2.4673 × 10-7 demonstrating a great affinity for SNRPG binding to Hsp70.14. CONCLUSIONS: The results suggest a possible involvement between the two proteins in hostile tumour microenvironments. Furthermore, these findings offer a different therapeutic perspective that could pave the way for the creation of novel small molecule inhibitors as drugs for the treatment of cancer.

6.
Microorganisms ; 10(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36013946

RESUMO

Crops aimed at feeding an exponentially growing population are often exposed to a variety of harsh environmental factors. Although plants have evolved ways of adjusting their metabolism and some have also been engineered to tolerate stressful environments, there is still a shortage of food supply. An alternative approach is to explore the possibility of using rhizosphere microorganisms in the mitigation of abiotic stress and hopefully improve food production. Several studies have shown that rhizobacteria and mycorrhizae organisms can help improve stress tolerance by enhancing plant growth; stimulating the production of phytohormones, siderophores, and solubilizing phosphates; lowering ethylene levels; and upregulating the expression of dehydration response and antioxidant genes. This article shows the secretion of secondary metabolites as an additional mechanism employed by microorganisms against abiotic stress. The understanding of these mechanisms will help improve the efficacy of plant-growth-promoting microorganisms.

7.
Biology (Basel) ; 11(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36009783

RESUMO

The United Nations (UN) estimate that the global population will reach 10 billion people by 2050. These projections have placed the agroeconomic industry under immense pressure to meet the growing demand for food and maintain global food security. However, factors associated with climate variability and the emergence of virulent plant pathogens and pests pose a considerable threat to meeting these demands. Advanced crop improvement strategies are required to circumvent the deleterious effects of biotic and abiotic stress and improve yields. Metabolomics is an emerging field in the omics pipeline and systems biology concerned with the quantitative and qualitative analysis of metabolites from a biological specimen under specified conditions. In the past few decades, metabolomics techniques have been extensively used to decipher and describe the metabolic networks associated with plant growth and development and the response and adaptation to biotic and abiotic stress. In recent years, metabolomics technologies, particularly plant metabolomics, have expanded to screening metabolic biomarkers for enhanced performance in yield and stress tolerance for metabolomics-assisted breeding. This review explores the recent advances in the application of metabolomics in agricultural biotechnology for biomarker discovery and the identification of new metabolites for crop improvement. We describe the basic plant metabolomics workflow, the essential analytical techniques, and the power of these combined analytical techniques with chemometrics and chemoinformatics tools. Furthermore, there are mentions of integrated omics systems for metabolomics-assisted breeding and of current applications.

8.
Adv Pharm Bull ; 12(2): 283-297, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35620337

RESUMO

Human schistosomiasis is a disease that mostly plagues the destitute of various tropical and sub-tropical countries, particularly in sub-Saharan Africa (SSA) and South America. It has significant effects on various health and economic-related matters. Globally, the burden of schistosomiasis has been controlled with a single chemotherapeutic drug, praziquantel (PZQ), which has recently demonstrated several clinical issues, including its inability to destroy juvenile schistosome worms and drug resistance because of its extensive use. The use of organometallic moieties in biological and medicinal chemistry has developed greatly and has led to their use in various anti-cancer and anti-infectious agents. The abundance of a range of organometallic compounds that can cause damage to the parasite has received tremendous feedback, with many already at clinical trials. The distinct redox biology of the schistosome parasite is a vulnerable element to the survival of the worm and has steered attempts toward the use of redox-directed bioorganometallic compounds. Disruption of the schistosome redox homeostasis through organometallic ions provides a novel drug target that could be used in overcoming the drawbacks of the mainstream drug and one that could possibly bypass the emergence of drug resistance.

9.
Adv Pharm Bull ; 12(2): 366-374, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35620338

RESUMO

Purpose: Universal stress protein (USP) from Schistosoma mansoni, designated as G4LZI3, waspreviously hypothesised as a druggable target and vaccine candidate for human schistosomiasis.The purpose of this study is to characterize a purified recombinant G4LZI3 preliminarily forsubsequent structural characterization, which will provide baseline structural data for futurefunctional studies for the discovery, design and development of new schistosomal drugs for thetreatment, control and elimination of schistosomiasis. Methods: Restriction digest analysis of a GenScript-synthesised codon-optimised G4LZI3gene construct was carried out to ascertain its integrity and size. Thereafter, the pQE30-G4LZI3 construct was transformed into an M15 bacterial expression host. Transformed cellswere induced with isopropyl ß-D-thiogalactoside for recombinant protein expression of anappreciable amount of pQE30-G4LZI3, which was subsequently purified with fast proteinliquid chromatography (FPLC) and a size exclusion chromatographic purification scheme.Preliminary biophysical characterization of the 6X His-tagged G4LZI3 was done to determineits secondary structure characteristics and protein stability. Results: A molecular weight protein of 20.3 kDa was confirmed subsequent to restriction digestanalysis, while heterologous protein expression yielded a highly soluble and considerableamount of histidine-tagged G4LZI3 protein, which was successfully purified to homogeneity.Biophysical characterization indicated that the protein was well folded, heat-stable, had thefunctional groups and secondary structure composition required and was thus amenable tofurther structural characterization and determination. Conclusion: Biophysical characterization of purified G4LZI3 showed that further structuralstudies can be embarked upon on the use of G4LZI3 as a druggable target and possibly avaccine target against schistosomiasis via vaccinomics.

10.
Am J Transl Res ; 13(11): 12775-12785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956492

RESUMO

Regulatory core-splicing proteins are now becoming highly promising therapeutic targets for the development of anti-cancer drugs. SNRPG and RBBP6 are two good examples of regulatory core-splicing proteins involved in tumorigenesis and tumor development whose multi-functional role is primarily mediated by protein-protein interactions. Over the years, skepticism abutting from the two onco-proteins has been mounting. Suggestive evidence using yeast 2-hybrid technique observed possible involvement between SNRPG and the RING finger domain of RBBP6. However, the putative interaction remains elusive and yet to be characterized. In this study, we developed the first MST-based assay to confirm the interaction between SNRPG and the RING finger domain of RBBP6. The results demonstrated a strong binding affinity between SNRPG and the RING finger domain of RBBP6 with a KD in the low nanomolar concentration range of 3.1596 nM. The results are congruent with previous findings suggesting possible involvement between the two proteins in cancer-cell networks, thereby providing a new mechanistic insight into the interaction between SNRPG and the RING finger domain of RBBP6. The interaction is therapeutically relevant and represents a great milestone in the anti-cancer drug discovery space. Identification of small molecule inhibitors to modulate the binding affinity between the two proteins would therefore be a major breakthrough in the development of new PPI-focused anti-cancer drugs.

11.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639223

RESUMO

Universal stress proteins (USPs) were originally discovered in Escherichia coli over two decades ago and since then their presence has been detected in various organisms that include plants, archaea, metazoans, and bacteria. As their name suggests, they function in a series of various cellular responses in both abiotic and biotic stressful conditions such as oxidative stress, exposure to DNA damaging agents, nutrient starvation, high temperature and acidic stress, among others. Although a highly conserved group of proteins, the molecular and biochemical aspects of their functions are largely evasive. This is concerning, as it was observed that USPs act as essential contributors to the survival/persistence of various infectious pathogens. Their ubiquitous nature in various organisms, as well as their augmentation during conditions of stress, is a clear indication of their direct or indirect importance in providing resilience against such conditions. This paper seeks to clarify what has already been reported in the literature on the proposed mechanism of action of USPs in pathogenic organisms.


Assuntos
Bactérias/patogenicidade , Infecções Bacterianas/complicações , Fibrose Cística/patologia , Proteínas de Choque Térmico/metabolismo , Parasitos/patogenicidade , Esquistossomose/complicações , Animais , Fibrose Cística/etiologia , Fibrose Cística/metabolismo , Humanos , Schistosoma/patogenicidade
12.
Vaccines (Basel) ; 9(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34358178

RESUMO

Proteins hardly function in isolation; they form complexes with other proteins or molecules to mediate cell signaling and control cellular processes in various organisms. Protein interactions control mechanisms that lead to normal and/or disease states. The use of competitive small molecule inhibitors to disrupt disease-relevant protein-protein interactions (PPIs) holds great promise for the development of new drugs. Schistosome invasion of the human host involves a variety of cross-species protein interactions. The pathogen expresses specific proteins that not only facilitate the breach of physical and biochemical barriers present in skin, but also evade the immune system and digestion of human hemoglobin, allowing for survival in the host for years. However, only a small number of specific protein interactions between the host and parasite have been functionally characterized; thus, in-depth understanding of the molecular mechanisms of these interactions is a key component in the development of new treatment methods. Efforts are now focused on developing a schistosomiasis vaccine, as a proposed better strategy used either alone or in combination with Praziquantel to control and eliminate this disease. This review will highlight protein interactions in schistosomes that can be targeted by specific PPI inhibitors for the design of an alternative treatment to Praziquantel.

13.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281269

RESUMO

The host-parasite schistosome relationship relies heavily on the interplay between the strategies imposed by the schistosome worm and the defense mechanisms the host uses to counter the line of attack of the parasite. The ultimate goal of the schistosome parasite entails five important steps: evade elimination tactics, survive within the human host, develop into adult forms, propagate in large numbers, and transmit from one host to the next. The aim of the parasitized host on the other hand is either to cure or limit infection. Therefore, it is a battle between two conflicting aspirations. From the host's standpoint, infection accompanies a plethora of immunological consequences; some are set in place to defend the host, while most end up promoting chronic disease, which ultimately crosses paths with oxidative stress and cancer. Understanding these networks provides attractive opportunities for anti-schistosome therapeutic development. Hence, this review discusses the mechanisms by which schistosomes modulate the human immune response with ultimate links to oxidative stress and genetic instability.


Assuntos
Citocinas/metabolismo , Interações Hospedeiro-Parasita/imunologia , Esquistossomose/imunologia , Esquistossomose/metabolismo , Animais , Linfócitos B Reguladores/imunologia , Basófilos/imunologia , Células Dendríticas/imunologia , Eosinófilos/imunologia , Humanos , Macrófagos/imunologia , Mastócitos/imunologia , MicroRNAs/imunologia , Modelos Imunológicos , Estresse Oxidativo , Schistosoma/imunologia , Schistosoma/patogenicidade , Esquistossomose/parasitologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia
14.
Curr Drug Discov Technol ; 18(5): e01102020186453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33001015

RESUMO

BACKGROUND: For decades, Praziquantel has been the undisputed drug of choice for all schistosome infections, but rising concerns due to the unelucidated mechanism of action of the drug and unavoidable reports of emerging drug resistant strains has necessitated the need for alternative treatment drug. Moreover, current apprehension has been reinforced by total dependence on the drug for treatment hence, the search for novel and effective anti-schistosomal drugs. METHODS: This study made use of bioinformatic tools to determine the structural binding of the Universal G4LZI3 Stress Protein (USP) in complex with ten polyphenol compounds, thereby highlighting the effectiveness of these recently identified 'lead' molecules in the design of novel therapeutics targeted against schistosomiasis. Upregulation of the G4LZI3 USP throughout the schistosome multifaceted developmental cycle sparks interest in its potential role as a druggable target. The integration of in silico tools provides an atomistic perspective into the binding of potential inhibitors to target proteins. This study therefore, implemented the use of Molecular Dynamic (MD) simulations to provide functional and structural insight into key conformational changes upon binding of G4- ZLI3 to these key phenolic compounds. RESULTS: Post-MD analyses revealed unique structural and conformational changes in the G4LZI3 protein in complex with curcumin and catechin respectively. These systems exhibited the highest binding energies, while the major interacting residues conserved in all the complexes provides a route map for structure-based drug design of novel compounds with enhanced inhibitory potency against the G4LZI3 protein. CONCLUSION: This study suggests an alternative approach for the development of anti-schistosomal drugs using natural compounds.


Assuntos
Proteínas de Choque Térmico , Esquistossomose , Desenho de Fármacos , Humanos , Simulação de Dinâmica Molecular
15.
Curr Drug Discov Technol ; 18(4): 473-484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32767945

RESUMO

Schistosome infection is regarded as one of the most important and neglected tropical diseases associated with poor sanitation. Like other living organisms, schistosomes employ multiple biological processes, of which some are regulated by a post-translational modification called Adenosine Diphosphate-ribosylation (ADP-ribosylation), catalyzed by ADP-ribosyltransferases. ADP-ribosylation is the addition of ADP-ribose moieties from Nicotinamide Adenine Dinucleotide (NAD+) to various targets, which include proteins and nucleotides. It is crucial in biological processes such as DNA repair, apoptosis, carbohydrate metabolism and catabolism. In the absence of a vaccine against schistosomiasis, this becomes a promising pathway in the identification of drug targets against various forms of this infection. The tegument of the worm is an encouraging immunogenic target for anti-schistosomal vaccine development. Vaccinology, molecular modeling and target-based drug discovery strategies have been used for years in drug discovery and for vaccine development. In this paper, we outline ADP-ribosylation and other different approaches to drug discovery and vaccine development against schistosomiasis.


Assuntos
ADP-Ribosilação/imunologia , Anti-Helmínticos/farmacologia , Doenças Negligenciadas/terapia , Schistosoma/imunologia , Esquistossomose/terapia , ADP-Ribosilação/efeitos dos fármacos , Animais , Anti-Helmínticos/uso terapêutico , Antígenos de Helmintos/imunologia , Descoberta de Drogas/métodos , Humanos , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/parasitologia , Schistosoma/efeitos dos fármacos , Esquistossomose/imunologia , Esquistossomose/parasitologia , Desenvolvimento de Vacinas/métodos
16.
J Diabetes Metab Disord ; 19(1): 469-481, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32550199

RESUMO

BACKGROUND: Gongronema latifolium leaf is used traditionally to treat diabetes and other diseases. The present study aimed to provide the modulatory effect of G. latifolium on hyperglycemia, inhibitory effect of redox imbalance and inflammation in alloxan-induced nephropathy in Wistar rats. METHODS: Alloxan monohydrate was used to induce diabetes by an intraperitoneal injection of (150 mg/kg). Three diabetic groups were administered aqueous leaf extract of G. latifolium at 6.36, 12.72 and 25.44 mg/kg bodyweight (BW) respectively; a group was administered with metformin (5 mg/kg BW), while the other two were served as positive and negative control. Thereafter, fasting blood glucose, antioxidant enzymes, malondialdehyde (MDA) level, interleukin 2 and 6 were determined. RESULTS: G. latifolium leaf significantly (p < 0.05) reduced the alloxan-induced increases in blood glucose, MDA, interleukin 2 and interleukin 6 level and increased the alloxan-induced decreases in superoxide dismutase, catalase, glutathione peroxidase, glutathione reduced and glutathione transferase activity. All these changes compared with those of metformin-treated diabetic rats. CONCLUSION: The data from this study suggest that G. latifolium modulates glucose homeostasis as well as inhibiting redox imbalance and inflammation in diabetic rats, which may be attributed to the effects of its phytochemical constituents such as saponins, flavonoids and alkaloids. It also indicated that inhibition of inflammatory cytokines and redox imbalance are likely mechanisms by which G. latifolium leaf exert its antidiabetic action.

17.
J Evid Based Integr Med ; 25: 2515690X20916123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32423242

RESUMO

Artocarpus heterophyllus Lam (Moraceae) stem bark has been used locally in managing diabetes mellitus with sparse scientific information. This study investigates the in vitro antioxidant potential of polyphenolic-rich extract of A heterophyllus stem bark as well as its antidiabetic activity in streptozotocin-induced diabetic rats. Fifty male Wistar rats were used with the induction of diabetes by a single intraperitoneal injection of streptozotocin (45 mg/kg body weight) and were orally administered 400 mg/kg free and bound phenols of A heterophyllus stem bark. The animals were sacrificed on the 28th day of the experiment using the cervical dislocation method; antihyperglycemia and anti-inflammatory parameters were subsequently assessed. The polyphenolic extracts demonstrated antioxidant potentials (such as hydrogen peroxide and diphenyl-1-picrylhydrazyl), as well as strong inhibitory activity against amylase and glucosidase. There was a significant (P < .05) increase in glycogen, insulin concentration, pancreatic ß-cell scores (HOMA-ß), antioxidant enzymes and hexokinase activities, as well as glucose transporter concentration in diabetic animals administered the extracts and metformin. Also, a significant (P < .05) reduction in fasting blood glucose, lipid peroxidation, glucose-6-phosphatase, and all anti-inflammatory parameters were observed in diabetic rats administered the extracts and metformin. The extracts demonstrated antidiabetic potential, which may be useful in the management of diabetes mellitus.


Assuntos
Antioxidantes/farmacologia , Artocarpus , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Nigéria , Casca de Planta , Ratos , Ratos Wistar , Estreptozocina
18.
Pak J Pharm Sci ; 33(2): 523-529, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32276893

RESUMO

In this study, the effect of free and bound polyphenolic-rich extract of Syzygium cumini (Linn) Skeels leaf on antioxidant as well as α-amylase and α-glucosidase activities were determined using in vitro model. Polyphenolic-rich extract of Syzygium cumini (Linn) Skeels leaf was prepared accordingly and the capability of the extract to inhibit antioxidants as typified by ferric reducing power (FRAP) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) among other free radicals scavenging abilities were quantified spectrophotometrically, added to this, the activities of (α-amylase and α-glucosidase were also assessed. The bound phenolic extract exhibited more in vitro antioxidant properties as represented by their high radicals scavenging ability in all the free radicals evaluated. Also, the polyphenolic-rich extracts inhibited α-amylase and α-glucosidase, with bound phenolics showing significant (p<0.05) increase in a dose-dependent manner than free phenolics. Therefore, this study suggests the use of Syzygium cumini leaf as a nutraceutical in the management/ control of type II diabetes mellitus patients.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/enzimologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Syzygium , Animais , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Polifenóis/isolamento & purificação , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/metabolismo , Suínos , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
19.
Am J Transl Res ; 11(11): 6702-6716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814883

RESUMO

Small nuclear ribonucleoprotein polypeptide G (SNRPG), often referred to as Smith protein G (SmG), is an indispensable component in the biogenesis of spliceosomal uridyl-rich small nuclear ribonucleoprotein particles (U snRNPs; U1, U2, U4 and U5), which are precursors of both the major and minor spliceosome. SNRPG has attracted significant attention because of its implicated roles in tumorigenesis and tumor development. Suggestive evidence of its varying expression levels has been reported in different types of cancers, which include breast cancer, lung cancer, prostate cancer and colon cancer. The accumulating evidence suggests that the splicing machinery component plays a significant role in the initiation and progression of cancers. SNRPG has a wide interaction network, and its functions are predominantly mediated by protein-protein interactions (PPIs), making it a promising anti-cancer therapeutic target in PPI-focused drug technology. Understanding its roles in tumorigenesis and tumor development is an indispensable arsenal in the development of molecular-targeted therapies. Several antitumor drugs linked to splicing machinery components have been reported in different types of cancers and some have already entered the clinic. However, targeting SNRPG as a drug development tool has been an overlooked and underdeveloped strategy in cancer therapy. In this article, we present a comprehensive and perspective view on the oncogenic potential of SNRPG in PPI-focused drug discovery.

20.
Adv Pharm Bull ; 9(4): 510-520, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31857956

RESUMO

Chlorotoxin (CTX) is a minute 4 kDa protein made up of 36 amino acid residues, commonly known for its binding affinity to chloride channels and matrix metalloproteinase-2 (MMP-2) of glioma tumors of the spine and brain. This property and the possibility of conjugating this peptide to nanoparticles have enabled its diverse use in various biotechnological and biomedical applications for cancer treatment, such as in tumor imaging and radiotherapy. Because of the fascinating biological properties CTX possesses, elucidating its mechanism of action may hold promise for the development of new and effective therapeutic drugs, as well as more sensitive and highly specific cancer-screening kits. This article therefore reviews the currently known applications of CTX and suggests diverse ways in which it can be applied for the design of improved drugs and diagnostic tools for cancer.

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