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1.
Pharmaceutics ; 13(11)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34834310

RESUMO

Ceftriaxone has been a part of therapeutic regime for combating some of the most aggressive bacterial infections in the last few decades. However, increasing bacterial resistance towards ceftriaxone and other third generation cephalosporin antibiotics has raised serious clinical concerns especially due to their misuse in the COVID-19 era. Advancement in nanotechnology has converted nano-therapeutic vision into a plausible reality with better targeting and reduced drug consumption. Thus, in the present study, gold nanoparticles (GNPs) were synthesized by using ceftriaxone antibiotic that acts as a reducing as well as capping agent. Ceftriaxone-loaded GNPs (CGNPs) were initially characterized by UV-visible spectroscopy, DLS, Zeta potential, Electron microscopy and FT-IR. However, a TEM micrograph showed a uniform size of 21 ± 1 nm for the synthesized CGNPs. Further, both (CGNPs) and pure ceftriaxone were examined for their efficacy against Escherichia coli, Staphylococcus aureus, Salmonella abony and Klebsiella pneumoniae. CGNPs showed MIC50 as 1.39, 1.6, 1.1 and 0.9 µg/mL against E. coli, S. aureus, S. abony and K. pneumoniae, respectively. Interestingly, CGNPs showed two times better efficacy when compared with pure ceftriaxone against the tested bacterial strains. Restoring the potential of unresponsive or less efficient ceftriaxone via gold nanoformulations is the most alluring concept of the whole study. Moreover, applicability of the findings from bench to bedside needs further validation.

2.
Polymers (Basel) ; 13(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641026

RESUMO

Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.

3.
Folia Microbiol (Praha) ; 66(6): 897-916, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34699042

RESUMO

Recent advancement in manipulation techniques of gut microbiota either ex vivo or in situ has broadened its plausible applicability for treating various diseases including cardiovascular disease. Several reports suggested that altering gut microbiota composition is an effective way to deal with issues associated with managing cardiovascular diseases. However, actual translation of gut microbiota manipulation-based techniques into cardiovascular-therapeutic approach is still questionable. This review summarized the evidence on challenges, opportunities, recent development, and future prospects of gut microbiota manipulation for targeting cardiovascular diseases. Initially, issues associated with current cardiovascular diseases treatment strategy, association of gut microbiota with cardiovascular disease, and its influence on cardiovascular drugs were discussed, followed by applicability of gut microbiota manipulation as a cardiovascular disease intervention strategy along with its challenges and future prospects. Despite the fact that the gut microbiota is rugged, interventions like probiotics, prebiotics, synbiotics, fecal microbiota transplantation, fecal virome transplantation, antibiotics, diet changes, and exercises could manipulate it. Advanced techniques like administration of engineered bacteriophages and bacteria could also be employed. Intensive exploration revealed that if sufficiently controlled approach and proper monitoring were applied, gut microbiota could provide a compelling answer for cardiovascular therapy.


Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Probióticos , Simbióticos , Doenças Cardiovasculares/terapia , Transplante de Microbiota Fecal , Humanos , Prebióticos
4.
Pharmaceuticals (Basel) ; 14(9)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34577637

RESUMO

Alzheimer's disease (AD) is a progressive neurological disorder that affects 50 million people. Despite this, only two classes of medication have been approved by the FDA. Therefore, we have planned to develop therapeutics by multitarget approach. We have explored the library of 2029 natural product-like compounds for their multi-targeting potential against AD by inhibiting AChE, BChE (cholinergic pathway) MAO-A, and MOA-B (oxidative stress pathway) through in silico high-throughput screening and molecular dynamics simulation. Based on the binding energy of these target enzymes, approximately 189 compounds exhibited a score of less than -10 kcal/mol against all targets. However, none of the control inhibitors exhibited a binding affinity of less than -10 kcal/mol. Among these, the top 10 hits of compounds against all four targets were selected for ADME-T analysis. As a result, only F0850-4777 exhibited an acceptable range of physicochemical properties, drug-likeness, pharmacokinetics, and suitability for BBB permeation with high GI-A and non-toxic effects. The molecular dynamics study confirmed that F0850-4777 remained inside the binding cavity of targets in a stable conformation throughout the simulation and Prime-MM/GBSA study revealed that van der Waals' energy (ΔGvdW) and non-polar solvation or lipophilic energy (ΔGSol_Lipo) contribute favorably towards the formation of a stable protein-ligand complex. Thus, F0850-4777 could be a potential candidate against multiple targets of two pathophysiological pathways of AD and opens the doors for further confirmation through in vitro and in vivo systems.

5.
Curr Issues Mol Biol ; 43(2): 932-940, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34449548

RESUMO

Prostate cancer (PCa) is addressed as the second most common form of onco-threat worldwide and is usually considered as the major cause of mortality in men. Recent times have seen a surge in exploration of plant-derived components for alternative therapeutical interventions against different oncological malignancies. Dammarolic acid or Asiatic acid (AsA) is an aglycone asiaticoside that has been reported for its efficacy in several ailments including cancer. The current study aimed to investigate the anti-proliferative potency of AsA against human prostate cancer PC-3 cells. Purified AsA was diluted and PC-3 cells were exposed to 20, 40, and 80 µM concentration and incubated for 24 h. Post-exposure, PC-3 cells showcased a substantial loss of their viability at 20 µM (p < 0.05), moreover, this reduction in cell viability escalated proportionally with an increase in AsA at concentrations of 40 and 80 µM (p < 0.01; p < 0.001) respectively. AsA-impelled loss of cellular viability was also evident from the acridine orange-stained photomicrographs, which was also used to quantify the viable and apoptotic cells using Image J software. Additionally, quantification of ROS within PC-3 cells also exhibited an increase in DCF-DA-mediated fluorescence intensity post-exposure to AsA in a dose-dependent manner. AsA-induced apoptosis in PC-3 cells was shown to be associated with augmented activity of caspase-3 proportionally to the AsA concentrations. Thus, initially, this exploratory study explicated that AsA treatment leads to anti-proliferative effects in PC-3 cells by enhancing oxidative stress and inciting apoptosis en route to onset of nuclear fragmentation.


Assuntos
NF-kappa B/antagonistas & inibidores , Triterpenos Pentacíclicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Anti-Infecciosos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , NF-kappa B/metabolismo , Células PC-3 , Neoplasias da Próstata/metabolismo , Triterpenos/farmacologia
6.
Life (Basel) ; 11(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063122

RESUMO

OBJECTIVE: Brain tumors are the most challenging of all tumors and accounts for about 3% of all cancer allied deaths. The aim of the present review is to examine the brain tumor prevalence and treatment modalities available in the Kingdom of Saudi Arabia. It also provides a comprehensive analysis of the application of various nanotechnology-based products for brain cancer treatments along with their prospective future advancements. METHODS: A literature review was performed to identify and summarize the current status of brain cancer in Saudi Arabia and the scope of nanobiotechnology in its treatment. RESULTS: Depending upon the study population data analysis, gliomas, astrocytoma, meningioma, and metastatic cancer have a higher incidence rate in Saudi Arabia than in other countries, and are mostly treated in accordance with conventional treatment modalities for brain cancer. Due to the poor prognosis of cancer, it has an average survival rate of 2 years. Conventional therapy includes surgery, radiotherapy, chemotherapy, and a combination thereof, but these do not control the disease's recurrence. Among the various nanomaterials discussed, liposomes and polymeric nanoformulations have demonstrated encouraging outcomes for facilitated brain cancer treatment. CONCLUSIONS: Nanomaterials possess the capacity to overcome the shortcomings of conventional therapies. Polymer-based nanomaterials have shown encouraging outcomes against brain cancer when amalgamated with other nano-based therapies. Nonetheless, nanomaterials could be devised that possess minimal toxicity towards normal cells or that specifically target tumor cells. In addition, rigorous clinical investigations are warranted to prepare them as an efficient and safe modality for brain cancer therapy.

7.
Metab Brain Dis ; 36(5): 829-847, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33704660

RESUMO

Neurodegeneration-associated dementia disorders (NADDs), namely Alzheimer and Parkinson diseases, are developed by a significant portion of the elderly population globally. Extensive research has provided critical insights into the molecular basis of the pathological advancements of these diseases, but an efficient curative therapy seems elusive. A common attribute of NADDs is neuroinflammation due to a chronic inflammatory response within the central nervous system (CNS), which is primarily modulated by microglia. This response within the CNS is positively regulated by cytokines, chemokines, secondary messengers or cyclic nucleotides, and free radicals. Microglia mediated immune activation is regulated by a positive feedback loop in NADDs. The present review focuses on evaluating the crosstalk between inflammatory mediators and microglia, which aggravates both the clinical progression and extent of NADDs by forming a persistent chronic inflammatory milieu within the CNS. We also discuss the role of the human gut microbiota and its effect on NADDs as well as the suitability of targeting toll-like receptors for an immunotherapeutic intervention targeting the deflation of an inflamed milieu within the CNS.

8.
Molecules ; 26(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499241

RESUMO

The Food and Drug Administration (FDA) approved a new class of anti-diabetic medication (a sodium-glucose co-transporter 2 (SGLT2) inhibitor) in 2013. However, SGLT2 inhibitor drugs are under evaluation due to their associative side effects, such as urinary tract and genital infection, urinary discomfort, diabetic ketosis, and kidney problems. Even clinicians have difficulty in recommending it to diabetic patients due to the increased probability of urinary tract infection. In our study, we selected natural SGLT2 inhibitors, namely acerogenin B, formononetin, (-)-kurarinone, (+)-pteryxin, and quinidine, to explore their potential against an emerging uropathogenic bacterial therapeutic target, i.e., FimH. FimH plays a critical role in the colonization of uropathogenic bacteria on the urinary tract surface. Thus, FimH antagonists show promising effects against uropathogenic bacterial strains via their targeting of FimH's adherence mechanism with less chance of resistance. The molecular docking results showed that, among natural SGLT2 inhibitors, formononetin, (+)-pteryxin, and quinidine have a strong interaction with FimH proteins, with binding energy (∆G) and inhibition constant (ki) values of -5.65 kcal/mol and 71.95 µM, -5.50 kcal/mol and 92.97 µM, and -5.70 kcal/mol and 66.40 µM, respectively. These interactions were better than those of the positive control heptyl α-d-mannopyranoside and far better than those of the SGLT2 inhibitor drug canagliflozin. Furthermore, a 50 ns molecular dynamics simulation was conducted to optimize the interaction, and the resulting complexes were found to be stable. Physicochemical property assessments predicted little toxicity and good drug-likeness properties for these three compounds. Therefore, formononetin, (+)-pteryxin, and quinidine can be proposed as promising SGLT2 inhibitors drugs, with add-on FimH inhibition potential that might reduce the probability of uropathogenic side effects.


Assuntos
Adesinas de Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/prevenção & controle , Proteínas de Fímbrias/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Infecções Urinárias/prevenção & controle , Escherichia coli Uropatogênica/efeitos dos fármacos , Adesinas de Escherichia coli/química , Biologia Computacional , Simulação por Computador , Cumarínicos/química , Cumarínicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Infecções por Escherichia coli/etiologia , Proteínas de Fímbrias/química , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Simulação de Acoplamento Molecular , Quinidina/química , Quinidina/farmacologia , Transportador 2 de Glucose-Sódio/química , Inibidores do Transportador 2 de Sódio-Glicose/química , Infecções Urinárias/etiologia , Escherichia coli Uropatogênica/patogenicidade
9.
Pharmaceutics ; 12(11)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212921

RESUMO

Microneedles (MNs) are tiny needle like structures used in drug delivery through layers of the skin. They are non-invasive and are associated with significantly less or no pain at the site of administration to the skin. MNs are excellent in delivering both small and large molecules to the subjects in need thereof. There exist several strategies for drug delivery using MNs, wherein each strategy has its pros and cons. Research in this domain lead to product development and commercialization for clinical use. Additionally, several MN-based products are undergoing clinical trials to evaluate its safety, efficacy, and tolerability. The present review begins by providing bird's-eye view about the general characteristics of MNs followed by providing recent updates in the treatment of cancer using MNs. Particularly, we provide an overview of various aspects namely: anti-cancerous MNs that work based on sensor technology, MNs for treatment of breast cancer, skin carcinoma, prostate cancer, and MNs fabricated by additive manufacturing or 3 dimensional printing for treatment of cancer. Further, the review also provides limitations, safety concerns, and latest updates about the clinical trials on MNs for the treatment of cancer. Furthermore, we also provide a regulatory overview from the "United States Food and Drug Administration" about MNs.

10.
Nanomaterials (Basel) ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008104

RESUMO

The purpose of this study was to fabricate biostable inorganic silver nanoparticles (AgNPs) using fresh peel (aqueous) extract of Benincasa hispida. A fast, robust, and eco-friendly approach was used for the synthesis of AgNPs, where bioactive components of peel extract of B. hispida acted as reducing and stabilizing agents. Synthesized AgNPs were characterized using a UV-Vis spectrophotometer, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and electron microscopy. The synthesized nanoparticles exhibited maximum absorption at 418 nm under the typical AgNPs surface plasmon resonance band range. They depicted a mean size of 26 ± 2 nm with a spherical shape. Their therapeutic prospective was determined by evaluating their antimicrobial and anticancer potential. The bio-synthesized silver nanoparticles exhibited strong antimicrobial activity with minimum inhibitory concentration (MIC 50) values of 14.5, 8.6, 6.063, and 13.4 µg/mL against Staphylococcus aureus (ATCC 25923), Micrococcus luteus (ATCC 14593), Escherichia coli (ATCC 25922), and Klebsiella pneumonia (ATCC 13883), respectively. The biosynthesized AgNPs showed potent in vitro cytotoxicity against human cervical cancer cell line with a half maximal inhibitory concentration (IC50) value of 0.066 µg/mL; however, no cytotoxic effect was observed on normal human primary osteoblasts cell line. This study explored B. hispida extract and confirmed its effectiveness as a promising source in producing AgNPs that could be employed for several therapeutic applications.

11.
Pak J Pharm Sci ; 33(6(Supplementary)): 2847-2857, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33879446

RESUMO

Uropathogenic strains belonging to the Enterobacteriaceae family are considered one of factors for urinary tract infections, and type 1 pilus fimbrial adhesin (FimH) and beta lactamase CTX-M-15 play crucial roles in their pathogenesis and resistance. Thus, a promising approach is to explore dual-targeting therapeutic agents that act against both FimH and CTX-M-15. In the present study, active constituents of Nigella sativa were selected on the basis of significant activity against UTIs. Molecular docking was used to target active constituents of Nigella sativa to the active sites of FimH and CTX-M-15; these included thymoquinone, dithymoquinone, carvacrol, p-cymene, thymol, thymohydroquinone and longifolene. Dithymoquinone was found to be the most potent dual inhibitor, with binding energy of -7.01 and -5.38kcal/mol against CTX-M-15 and FimH, respectively; In addition, Dithymoquinone exhibited superior activity compared to positive controls avibactam and heptyl α-D-mannopyranoside. Further molecular dynamic simulation studies were carried out to assess the stability of dithymoquinone-target protein complexes via RMSD, Rg, SASA, hydrogen bond number, and RMSF analysis. Both protein-ligand complexes were conserved and attained equilibrium at around 2.0 to 2.5 ns during 10 ns runs. These results suggest that active constituents of Nigella sativa, particularly dithymoquinone, might represent a plausible therapeutic strategy against resistant uropathogenic bacteria.


Assuntos
Adesinas Bacterianas/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Nigella sativa/química , Infecções Urinárias/tratamento farmacológico , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana , Simulação de Acoplamento Molecular , Infecções Urinárias/microbiologia
12.
Int J Mol Sci ; 20(10)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109079

RESUMO

Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.


Assuntos
Anti-Infecciosos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Nanopartículas Metálicas , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óxido Nítrico/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Óxido de Zinco/química
13.
3 Biotech ; 9(3): 70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30800581

RESUMO

Cancer prevalence has increased at an alarming rate worldwide. Complexity, resistance mechanism and multiple compensatory survival pathways of cancer cells have abated the response of currently available cancer medications. Therefore, multi-target agents rather than single target might provide a better solution to these cancer therapy issues. In the present study, anti-PLK1 (Polo-like kinase 1) potential of the eight FDA-approved (2017) anti-cancer drugs have been explored using molecular docking approach. Out of all the tested drugs, brigatinib, niraparib and ribociclib showed better binding affinity towards the 'kinase domain' of PLK1. The Gibbs free binding energy (ΔG) and inhibition constant (K i) values for brigatinib, niraparib and ribociclib interaction with the kinase domain of PLK1 were '- 8.05 kcal/mol and 1.26 µM', '- 8.35 kcal/mol and 0.729 µM' and '- 7.29 kcal/mol and 4.52 µM', respectively. Interestingly, the docking results of these three drugs were better than the known PLK1 inhibitors (BI-2536 and rigosertib). The ΔG and K i values for BI-2536 and rigosertib interaction with the kinase domain of PLK1 were '- 6.8 kcal/mol and 10.38 µM' and '- 6.6 kcal/mol and 14.51 µM', respectively. Brigatinib, niraparib and ribociclib have been approved by FDA for the treatment of non-small cell lung cancer, ovarian/fallopian tube cancer and breast cancer, respectively. PLK1 is regarded as a potential cancer target, and it is specifically over-expressed in different types of cancer cells, including aforementioned cancers. Actually, the target enzymes for anti-cancer action of brigatinib, niraparib and ribociclib are tyrosine kinase, poly(ADP-ribose) polymerase and cyclin-dependent kinase 4/6, respectively. However, based on our outcomes, we could safely state that PLK1 might plausibly emerge as an add-on target for each of these three anti-cancer drugs. We strongly believe that this study would assist in the development of better dual-targeting cancer therapeutic agent in the near future.

14.
Biomed Pharmacother ; 107: 7-18, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30075371

RESUMO

Management of bacterial infections of central nervous system is a major challenge for the scientists all over the world. Despite the development of various potential drugs, the issue of central nervous system infections persists in the society. The main constraint is the delivery of drugs across the blood brain barrier and only a few drugs after meeting the stringent criteria could cross the blood brain barrier. On the other hand, certain bacterial pathogens could easily enter the brain by using several factors and mechanisms by crossing the blood brain barriers. Interestingly, in the recent past, gold nanoparticles have shown immense potential to overcome the issues associated with the treatment of central nervous system infections, especially due to their inherent ability to cross the blood brain barrier. Initially, the present review summarized the recent updates on the pathogenesis and factors involved in neurological bacterial infections, including the mechanism used by bacterial pathogens to cross the blood brain barriers. Thereafter, the emphasis of the review was on providing current information on gold nanoparticles pertinent to their applicability for the treatment of neurological infections. After discussing the background of neurological bacterial infections, the characteristic features, antibacterial properties, mechanisms of antibacterial action and ability to cross the blood brain barrier of gold nanoparticles have been summarized. Some of the features of gold nanoparticles that make them an ideal candidate for brain delivery are biocompatibity, stability, ability to get synthesized in different sizes with facile methods, surface affinity towards various functional groups, spontaneous crossing of blood brain barrier without applying any external field and most importantly, easy non-invasive tracing by CT imaging. The current updates on the development of gold nanoparticles based therapeutic strategies for the prevention and treatment of central nervous system infections have been discussed in the present study. However, further investigation would be required to translate these preclinical outcomes into clinical applications. Nevertheless, we could safely state that the information gathered and discussed in the present review would benefit the scientists working in the field of neuro-nanotechnology.


Assuntos
Infecções Bacterianas/terapia , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/patologia , Ouro/química , Nanopartículas Metálicas/química , Animais , Antibacterianos/uso terapêutico , Barreira Hematoencefálica/patologia , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade
15.
3 Biotech ; 8(8): 361, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30105186

RESUMO

Diabetes is a deteriorating metabolic ailment which negatively affects different organs; however, its prime target is insulin secreting pancreatic ß-cells. Although, different medications have been affirmed for diabetes management and numerous drugs are undergoing clinical trials, no significant breakthrough has yet been achieved. Available drugs either show some side effects or provide only short-term alleviation. The rationales behind the failure of current anti-diabetic treatment strategy are association of complex patho-physiologies and participation of various organs. Consequently, there is a critical need to search for multi-effect drugs that might impede various patho-physiological mechanisms related to diabetes. Fortunately, one natural compound could act on several diabetes linked targets. Thus, natural compounds might be regarded as a viable alternative choice to improve the progression as well as side effects of diabetes. Despite the fact that immense literatures are available on natural compounds indicating promising outcomes against diabetes, more systematic studies are still needed to establish them as effective anti-diabetic agents. Till date, we are unable to access all the information regarding modes of action, toxicity risks and physicochemical properties of anti-diabetic natural compounds on one platform. Hence, anti-diabetic natural compounds database (ADNCD) has been created to categorize each anti-diabetic natural compound on the basis of their mode of action and to provide compendious information of their physicochemical properties and toxicity risks. In short, ADNCD has imperative information for the researchers working in the field of diabetes drug development.

16.
Life Sci ; 209: 430-434, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30138593

RESUMO

Silver nanoparticles (AgNPs) have been used in various medicinal and commercial products because of their exceptional anti-microbial and anti-odor properties. On the other hand, increased commercialization of AgNPs containing products has led to its release into the environment. Thus, studies are needed to assess their impact on the environment as well as on human body. Several reports have shown that AgNPs could cause some serious neurotoxic effects. Most of these studies have been performed using chemically synthesized AgNPs. In contrast, green nanoparticles are usually considered safer than their chemically synthesized counterparts. Accordingly, in this research work, we have assessed the effect of AgNPs synthesized from aqueous-leaf-extract of Mentha piperita on one of the most important neurological enzymes i.e. acetylcholinesterase (AChE) to predict its neurotoxicity. M. piperita synthesized AgNPs were subjected to characterization by UV-visible-spectrometry, Scanning Electron-Microscopy as well as Transmission Electron-Microscopy. Here, the size of the AgNPs was found to be 35 nm with spherical shape. These AgNPs showed concentration-dependent inhibitory-effect on the AChE enzyme-activity displaying an IC50 of 150 nM. Further, kinetic analysis showed mixed type of inhibition, which means that AgNPs were capable of binding to both the free enzyme (AChE) and to the enzyme-substrate (AChE-acetylcholine) complex. These results suggest that even green synthesized AgNPs might cause neurotoxicity via inhibiting AChE activity. However, more studies are needed to elucidate the exact mechanism of neurotoxicity by AgNPs. Nevertheless, we could safely state that the present study provides relevant preliminary information regarding neurotoxicity of green synthesized AgNPs.


Assuntos
Acetilcolinesterase/química , Inibidores Enzimáticos/farmacologia , Mentha piperita/química , Nanopartículas Metálicas/administração & dosagem , Extratos Vegetais/farmacologia , Folhas de Planta/química , Prata/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Humanos , Cinética , Nanopartículas Metálicas/química , Extratos Vegetais/isolamento & purificação , Prata/isolamento & purificação
17.
Curr Drug Metab ; 19(8): 704-713, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29512457

RESUMO

BACKGROUND: Alzheimer's disease (AD) is recognized as progressive multifaceted and multi-factorial neurodegenerative disorder which causes dementia among elderly people. Although, researchers in this field have put considerable efforts for the investigation of novel and appropriate therapeutic measures towards the cure of AD, unfortunately, no effective prevention therapy for this disease is available till date. In fact, various aspects involved in the onset and progression of AD are still disputed or uncovered. However, to achieve definite and direct cure of AD, researcher's attention has been drawn towards exploration of new therapeutics targets. In this review, we have discussed the current progress of various aspects of pathophysiological mechanisms behind AD, together with recent investigational therapeutic approaches and present tools with an emphasis on Multi Target Directed Drugs approach. METHOD: We have scrutinized numerous peer-reviewed research articles to assemble and discuss significant research findings and success achieved in the last decade pertinent to the application of Multi-Target Directed Drugs in the treatment of AD. RESULTS: The main emphasis of the review was to understand the various aspects of pathophysiological mechanisms involved in AD, along with the recent developments on potential AD targets and application of Multi-Target Directed Drugs approach against AD. In addition, a brief overview of major drawbacks of conventional anti-AD drugs has also been included. We found that several strategies including in silico approach could be used for multi-target drug designing against AD. However, various synthetic/natural compounds and nano-formulations have the ability to be developed as multi-target drugs for AD. CONCLUSION: The present review comprises imperative information regarding AD pathology and disease process along with recent researches going on to develop treatment strategies against AD. Thus, this review might be helpful for physician, neurologist and scientist in understanding the diverse roots of AD for designing primary cure skills and scaffold of pharmacological treatment to manage AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Nootrópicos/farmacologia , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Cognição/efeitos dos fármacos , Simulação por Computador , Desenho de Fármacos , Humanos , Terapia de Alvo Molecular/métodos , Nootrópicos/uso terapêutico , Resultado do Tratamento
18.
Curr Drug Metab ; 19(12): 1002-1011, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29600757

RESUMO

BACKGROUND: Liver ailments including alcoholic liver disease (ALD), still remain the main reason for morbidity & mortality worldwide. In fact, ALD is a multifactorial disease with complex pathophysiology which is linked to several types of liver damages including steatohepatitis, fibrosis and cirrhosis. METHODS: This review emphasizes on 30 herbal medicinal plants with their extracts studied for protective effect against ALD and current scientific evidence of ALD cure by thirty Indian Materia Medica including Tilia Platyphyllos, Amomum subulatum, Carica papaya, Pogostemon patchouli, Commelina benghalensis, Bacopamonnieri, Pecan nut, Allium cepa, Beta Vulgaris, Adina cordifolia, Ocimum gratissimum, Vernonia amygdalina, Sida veronicaefolia, Chenopodium album, Korean red ginseng, Elephantopus scaber, Tecomella undulata, Prunus armeniaca, Sea tangle (Laminaria japonica), Emblica officinalis, Saccharum officinarum, Cocculus hirsutus, Cassia roxburghii, Zhi-Zi-Da- Huang, Phyllanthus amarus, Aegle marmelos, Agrimonia eupatoria, Flaveria trinervia, Curcuma longa and Garcinia indica. RESULTS: Reduction in oxidative stress, improvement in inflammation, reduction in degeneration of fat and necrosis are some of the mechanisms of action of these medicinal plants observed in alcohol induced in-vivo and in-vitro liver injury models. CONCLUSION: Accordingly, this review provides several evidences which show that these medicinal plants could be used for the treatment and prevention of ALD.


Assuntos
Hepatopatias Alcoólicas/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Substâncias Protetoras/uso terapêutico , Animais
19.
Curr Drug Metab ; 18(9): 842-852, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28595531

RESUMO

BACKGROUND: Drug repurposing is an innovative approach as it provides new indications for already approved and established drugs. Due to high failure rates and cost involved in traditional drug development procedures, many pharmaceutical companies are primarily focusing on drug repurposing strategy. In Alzheimer disease (AD), existing therapeutic agents only provide symptomatic benefits and does not play a role in disease modification, therefore, an alternative strategy of repurposing can be used to inhibit neurodegeneracy process and other pathological complications. This review discusses the beneficial effects of available licensed drug compounds which can be used as repurposed drugs for the treatment of AD. Moreover, it includes a brief overview of current treatment strategies, including therapies based on nanotechnology and their limitations. METHODS: We attempted an organized scan of peer-reviewed research articles pertinent to licensed drugs that showed beneficial effects in Alzheimer's pathology. Our search includes in vitro studies, epidemiological data and clinical trials. In fact, we have collected, scrutinized, analyzed and discussed all the data that suggested the plausible application of repurposed drugs for the treatment of AD. RESULTS: Cholinesterase inhibitors and N-methyl-D-Aspartate receptor antagonist are available options to improve the cognitive functions of Alzheimer's patients. These drugs only help in balancing disturbed level of neurotransmitters and are not helpful in disease modification. On the other hand, the nanotechnological based approach has promised to solve some challenges, but has certain limitations such as biocompatibility issues, therefore, it requires an extensive amount of research work. As our main emphasis was on repurposed drugs, we have performed an extensive review of articles to identify compounds that have been approved by the United States Food and Drug Administration for the treatment of diseases other than Alzheimer's but might have an impact on AD modification based on clinical evidences. Amyloid clearance, tau pathology and anti-inflammatory mechanisms are potential factors that are taken into consideration for disease modification. In addition, the role of bioinformatics and in silico drug repurposing strategy is crucial in the field of drug research, and plays a significant role in the identification of potential repurposed drugs. Thus, we have also mentioned several drug repurposing computational tools that are robust and can predict reliable results based on available gene expression data. DISCUSSION: The major advantage of repurposing strategy is the identification of drug compounds with known mechanism of action, toxicology information and pharmacodynamics profiles; hence, less time is required for devising AD modification treatment. There are some issues as well with this method, which can be resolved by extending our research in this domain. CONCLUSION: AD is incurable, and there is an urgent need to find new treatments, as it is affecting the number of families and society overall. The drug repurposing approach is gaining attention in the pharmaceutical world, as it can substantially reduce the time and cost required to advance any treatment to the stage of clinical trials..


Assuntos
Doença de Alzheimer/tratamento farmacológico , Reposicionamento de Medicamentos , Animais , Biologia Computacional , Humanos , Resultado do Tratamento
20.
J Cell Biochem ; 118(9): 2802-2808, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28181300

RESUMO

Multidrug-resistance due to "ß lactamases having the expanded spectrum" (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX-M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug-resistance in ESBL producing strains. Here, two CTX-M-15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of "cefotaxime loaded gold-nanoparticles." Bromelain was used for both reduction and capping in the process of synthesis of gold-nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV-Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth-dilution method for the estimation of the antibacterial-activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802-2808, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Cefotaxima , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Ouro , Klebsiella pneumoniae/crescimento & desenvolvimento , Nanopartículas Metálicas/química , Cefotaxima/química , Cefotaxima/farmacologia , Ouro/química , Ouro/farmacologia
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