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1.
Parkinsonism Relat Disord ; 115: 105799, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37633805

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the exact etiology of PD remains elusive, growing evidence suggests a complex interplay of genetic, environmental, and lifestyle factors in its development. Despite advances in pharmacological interventions, current treatments primarily focus on managing symptoms rather than altering the disease's underlying course. In recent years, natural phytocompounds have emerged as a promising avenue for PD management. Phytochemicals derived from plants, such as phenolic acids, flavones, phenols, flavonoids, polyphenols, saponins, terpenes, alkaloids, and amino acids, have been extensively studied for their potential neuroprotective effects. These bioactive compounds possess a wide range of therapeutic properties, including antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, which may counteract the neurodegenerative processes in PD. This comprehensive review delves into the pathophysiology of PD, with a specific focus on the roles of oxidative stress, mitochondrial dysfunction, and protein malfunction in disease pathogenesis. The review collates a wealth of evidence from preclinical studies and in vitro experiments, highlighting the potential of various phytochemicals in attenuating dopaminergic neuron degeneration, reducing α-synuclein aggregation, and modulating neuroinflammatory responses. Prominent among the natural compounds studied are curcumin, resveratrol, coenzyme Q10, and omega-3 fatty acids, which have demonstrated neuroprotective effects in experimental models of PD. Additionally, flavonoids like baicalein, luteolin, quercetin, and nobiletin, and alkaloids such as berberine and physostigmine, show promise in mitigating PD-associated pathologies. This review emphasizes the need for further research through controlled clinical trials to establish the safety and efficacy of these natural compounds in PD management. Although preclinical evidence is compelling, the translation of these findings into effective therapies for PD necessitates robust clinical investigation. Rigorous evaluation of pharmacokinetics, bioavailability, and potential drug interactions is imperative to pave the way for evidence-based treatment strategies. With the rising interest in natural alternatives and the potential for synergistic effects with conventional therapies, this review serves as a comprehensive resource for pharmaceutical industries, researchers, and clinicians seeking novel therapeutic approaches to combat PD. Harnessing the therapeutic potential of these natural phytocompounds may hold the key to improving the quality of life for PD patients and moving towards disease-modifying therapies in the future.


Assuntos
Alcaloides , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Qualidade de Vida , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Neurônios Dopaminérgicos/patologia , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Gerenciamento Clínico
2.
Front Pharmacol ; 14: 1276209, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38239204

RESUMO

Background: Ovarian cancer, colloquially termed the "silent killer" among gynecological malignancies, remains elusive due to its often-asymptomatic progression and diagnostic challenges. Central to its pathogenesis is the overactive PI3K/Akt/mTOR signaling pathway, responsible for various cellular functions, from proliferation to survival. Within this context, the phytochemical compounds mangiferin (derived from Mangifera indica) and curcumin (from Curcuma longa) stand out for their potential modulatory effects. However, their inherent bioavailability challenges necessitate innovative delivery systems to maximize therapeutic benefits. Objective: This study seeks to synergize the merits of nanotechnology with the therapeutic properties of mangiferin and curcumin, aiming to bolster their efficacy against ovarian cancer. Methods: Employing specific nanotechnological principles, we engineered exosomal and liposomal nano-carriers for mangiferin and curcumin, targeting the PI3K/Akt/mTOR pathway. Molecular docking techniques mapped the interactions of these phytochemicals with key proteins in the pathway, analyzing their binding efficiencies. Furthermore, molecular dynamics simulations, spanning 100 nanoseconds, verified these interactions, with additional computational methodologies further validating our findings. The rationale for the 100 nanoseconds time span lies in its sufficiency to observe meaningful protein-ligand interactions and conformational changes. Notably, liposomal technology provided an enhancement in drug delivery by protecting these compounds from degradation, allowing controlled release, and improving cellular uptake. Results: Our computational investigations demonstrated notable binding affinities of mangiferin and curcumin: PI3K at -11.20 kcal/mol, Akt at -15.16 kcal/mol, and mTOR at -10.24 kcal/mol. The adoption of exosome/liposome-mediated delivery significantly amplified the bioavailability and cellular uptake of these nano-formulated compounds, positioning them as potential stalwarts in ovarian cancer intervention. A brief explanation of exosome/liposome-mediated delivery involves the use of these vesicles to encapsulate and transport therapeutic agents directly to the target cells, enhancing drug delivery efficiency and minimizing side effects. Conclusion: Addressing ovarian cancer's intricacies, dominated by the erratic PI3K/Akt/mTOR signaling, mandates innovative therapeutic strategies. Our pioneering approach converges nanotechnological liposomal delivery with mangiferin and curcumin's natural efficacies. This confluence, validated by computational insights, heralds a paradigm shift in ovarian cancer treatment. As our findings underscore the collaborative potential of these phytochemicals, it beckons further exploration in translational studies and clinical applications, ensuring the best intersection of nature and technology for therapeutic advantage.

3.
Materials (Basel) ; 15(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36431686

RESUMO

Herein, zinc oxide nanoparticles (ZnO NPs) were greenly synthesized from Tridax procumbens aqueous leaf extract (TPE) and characterized physically (e.g., Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM)) and biologically (test of their anti-diabetic activity). Anti-diabetic activities of TPE and TPE-derived ZnO NPs have been carried out in a streptozotocin (STZ)­induced diabetic rat model. Diabetes mellitus (DM) was induced with a single intraperitoneal dosage of the glucose analogue STZ (55 mg/Kg) known to be particularly toxic to pancreatic insulin-producing beta-cells. TPE and TPE-derived ZnO NPs were administered orally, once every day for 21 days in diabetic rats, at 100 and 200 mg/Kg, respectively. The standard antidiabetic medication, glibenclamide, was used as a control at a dose of 10 mg/Kg. Various parameters were investigated, including bodyweight (bw) variations, glycemia, lipidaemia, glycated hemoglobin (HbA1c), and histopathological alterations in the rat's liver and pancreas. The TPE-mediated NPs were small, spherical, stable, and uniform. Compared to TPE and, to a lesser extent, glibenclamide, TPE-derived ZnO NPs lowered blood glucose levels considerably (p < 0.05) and in a dose-dependent manner while preventing body weight loss. Further, positive benefits for both the lipid profile and glycated hemoglobin were also noticed with TPE-derived ZnO NPs. The histopathological assessment revealed that synthesized TPE-derived ZnO NPs are safe, non-toxic, and biocompatible. At 200 mg/Kg/day, TPE-derived ZnO NPs had a more substantial hypoglycemic response than at 100 mg/Kg/day. Thus, in this first reported experimental setting, ZnO NPs biosynthesized from the leaf extract of Tridax procumbens exert more potent anti-diabetic activity than TPE and glibenclamide. We conclude that such a greenly prepared nanomaterial may be a promising alternative or complementary (adjuvant) therapy, at least to the current Indian's traditional medicine system. Translational findings are prompted in human populations to determine the efficacy of these NPs.

4.
J Trop Med ; 2022: 4952221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187457

RESUMO

Several medicinal plants have the potential to be a promising alternative pharmacological therapy for a variety of human illnesses. Many insects, including mosquitoes, are important vectors of deadly pathogens and parasites, which in the world's growing human and animal populations can cause serious epidemics and pandemics. Medicinal plants continue to provide a large library of phytochemicals, which can be used to replace chemically synthesized insecticides, and utilization of herbal product-based insecticides is one of the best and safest alternatives for mosquito control. Identifying new effective phyto-derived insecticides is important to counter increasing insect resistance to synthetic compounds and provide a safer environment. Solanum genus (Solanaceae family or nightshades) comprises more than 2500 species, which are widely used as food and traditional medicine. All research publications on insecticidal properties of Solanaceae plants and their phytoconstituents against mosquitoes and other insects published up to July 2020 were systematically analyzed through PubMed/MEDLINE, Scopus, EBSCO, Europe PMC, and Google Scholar databases, with focus on species containing active phytoconstituents that are biodegradable and environmentally safe. The current state of knowledge on larvicidal plants of Solanum species, type of extracts, target insect species, type of effects, name of inhibiting bioactive compounds, and their lethal doses (LC50 and LC90) were reviewed in this study. These studies provide valuable information about the activity of various species of Solanum and their phytochemical diversity, as well as a roadmap for optimizing select compounds for botanical repellents against a variety of vectors that cause debilitating and life-threatening human diseases.

5.
Pak J Pharm Sci ; 35(4(Special)): 1201-1208, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36218098

RESUMO

The aim of this study was to analyze gastrointestinal, respiratory and vascular pharmacological effects of 70% hydro-alcoholic extract of Calligonum polygonoides (Cp. Cr) in animal models. All the procedures were carried-out as per previous literature with slight modification where necessary. It was found that Cp. Cr affected significant relaxation of spontaneous and K+ (80 mM) induced contractions. The results showed a corresponding shift of calcium concentration response curves. Similarly Cp. Cr showed relaxant effect on trachea in carbachol (Cch) induced tracheal contractions. Moreover, contractions induced by phenylephrine (1µM) in quarantine rabbit aortic preparations causes Cp. Cr induced relaxation of aortal contractions. Verapamil was used as a standard calcium channel blocker. The findings of this study suggested vasodilator, bronchodilator and spasmolytic effects of Cp. Cr.


Assuntos
Parassimpatolíticos , Polygonaceae , Animais , Broncodilatadores/farmacologia , Cálcio , Bloqueadores dos Canais de Cálcio/farmacologia , Carbacol/farmacologia , Jejuno , Modelos Animais , Parassimpatolíticos/farmacologia , Fenilefrina/farmacologia , Extratos Vegetais/farmacologia , Coelhos , Traqueia , Vasodilatadores/farmacologia , Verapamil/farmacologia
6.
Drug Deliv ; 29(1): 2773-2783, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36036168

RESUMO

Based on the administration convenience, transmucosal buccal drug delivery allows special strength points over peroral routes for systemic delivery. It could achieve local or systemic effect and boost drugs' bioavailability for agents with first pass metabolism. The current study aimed to manufacture and optimize a lavender oil-based nanoemulsion loaded with zaleplon and incorporate it into fast-disintegrating tablets to promote its dissolution and oral bioavailability via oral mucosa. Zaleplon-loaded nanoemulsions were devised with various levels of lavender oil (10% to 25%), the surfactant Sorbeth-20 (35% to 65%), and the co-surfactant HCO-60 (20% to 40%); the extreme vertices mixture statistical design was adopted. The droplet size and drug-loading efficiency were the evaluated. The optimal formulation was transformed into self-nanoemulsified lyophilized tablets (ZP-LV-SNELTs), which were tested for their uniformity of content, friability, and disintegration time with in-vitro release. Finally, the pharmacokinetic parameters of the ZP-LV-SNELTs were determined and compared with those of marketed formulations. The optimal nanoemulsion had a droplet size of 87 nm and drug-loading capacity of 185 mg/mL. ZP-LV-SNELTs exhibited acceptable friability and weight uniformity and a short disintegration time. The in-vitro release of ZP-LV-SNELTs was 17 times faster than that of the marketed tablet. Moreover, the optimal ZP-LV-SNELTs increased the bioavailability of zaleplon in rabbits by 1.6-fold compared with the commercial tablets. Hence, this investigation revealed that ZP-LV-SNELTs delivered zaleplon with enhanced solubility, a fast release, and boosted bioavailability thru oral mucosa which provided a favorable route for drug administration which is suggested to be clinically investigated in future studies.


Assuntos
Sistemas de Liberação de Medicamentos , Tensoativos , Acetamidas , Administração Oral , Animais , Disponibilidade Biológica , Emulsões , Lavandula , Óleos Voláteis , Óleos de Plantas , Pirimidinas , Coelhos , Solubilidade , Comprimidos
7.
Molecules ; 27(14)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35889525

RESUMO

Oxidative stress is the key factor that strengthens free radical generation which stimulates lung inflammation. The aim was to explore antioxidant, bronchodilatory along with anti-asthmatic potential of folkloric plants and the aqueous methanolic crude extract of Ipomoea nil (In.Cr) seeds which may demonstrate as more potent, economically affordable, having an improved antioxidant profile and providing evidence as exclusive therapeutic agents in respiratory pharmacology. In vitro antioxidant temperament was executed by DPPH, TFC, TPC and HPLC in addition to enzyme inhibition (cholinesterase) analysis; a bronchodilator assay on rabbit's trachea as well as in vivo OVA-induced allergic asthmatic activity was performed on mice. In vitro analysis of 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) expressed as % inhibition 86.28 ± 0.25 with IC50 17.22 ± 0.56 mol/L, TPC 115.5 ± 1.02 mg GAE/g of dry sample, TFC 50.44 ± 1.06 mg QE/g dry weight of sample, inhibition in cholinesterase levels for acetyl and butyryl with IC50 (0.60 ± 0.67 and 1.5 ± 0.04 mol/L) in comparison with standard 0.06 ± 0.002 and 0.30 ± 0.003, respectively, while HPLC characterization of In.Cr confirmed the existence with identification as well as quantification of various polyphenolics and flavonoids i.e., gallic acid, vanillic acid, chlorogenic acid, quercetin, kaempferol and others. However, oral gavage of In.Cr at different doses in rabbits showed a better brochodilation profile as compared to carbachol and K+-induced bronchospasm. More significant (p < 0.01) reduction in OVA-induced allergic hyper-responses i.e., inflammatory cells grade, antibody IgE as well as altered IFN-α in airways were observed at three different doses of In.Cr. It can be concluded that sound mechanistic basis i.e., the existence of antioxidants: various phenolic and flavonoids, calcium antagonist(s) as well as enzymes' inhibition profile, validates folkloric consumptions of this traditionally used plant to treat ailments of respiration.


Assuntos
Antioxidantes , Ipomoea nil , Animais , Antioxidantes/análise , Colinesterases , Flavonoides/análise , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Folclore , Camundongos , Ovalbumina , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Coelhos
8.
Molecules ; 27(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35889240

RESUMO

Suaeda fruticosa Forssk. Ex J.F.Gmel is traditionally used for inflammatory and digestive disorders, as a carminative, and for diarrhea. This plant is widely distributed in Asia, Africa, and the Mediterranean region. Aqueous methanolic extract of S. fruticosa (Sf.Cr) was prepared and screened for phytoconstituents through qualitative and GC-MS analysis. Quantification of total phenolic and flavonoid contents was performed, while antioxidant capacity was determined by DPPH, CUPRAC, FRAP, and ABTS assays. The gastroprotective activity was assessed in an ethanol-induced ulcer model. Gastric secretory parameters and macroscopic ulcerated lesions were analyzed and scored for ulcer severity. After scoring, histopathology was performed, and gastric mucus contents were determined. Oral pre-treatment of Sf.Cr demonstrated significant gastroprotection. The gastric ulcer severity score and ulcer index were reduced while the %-inhibition of ulcer was increased dose-dependently. The Sf.Cr significantly elevated the pH of gastric juice, while a decrease in total acidity and gastric juice volume was observed. Histopathology demonstrated less oedema and neutrophil infiltration in gastric mucosa of rats pre-treated with the Sf.Cr in comparison to ethanol-intoxicated animals. Furthermore, the gastric mucus contents were increased as determined by alcian blue binding. Sf.Cr showed marked gastroprotective activity, which can be attributed to antioxidant, antisecretory, and cytoprotective effects.


Assuntos
Antiulcerosos , Chenopodiaceae , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antioxidantes/metabolismo , Etanol/metabolismo , Mucosa Gástrica , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Úlcera/tratamento farmacológico
9.
Molecules ; 27(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35684321

RESUMO

Rumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius's therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005−0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases.


Assuntos
Infarto do Miocárdio , Rumex , Animais , Cardiotoxicidade/tratamento farmacológico , Catecolaminas , Epinefrina , Infarto do Miocárdio/tratamento farmacológico , Necrose/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Coelhos , Vasodilatadores/farmacologia
10.
Curr Alzheimer Res ; 19(6): 420-439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692129

RESUMO

INTRODUCTION: Alzheimer's disease (AD) is a progressive, neurodegenerative disease that severely affects individuals' cognitive abilities, memory, and quality of life. It affects the elderly population, and there is no permanent prevention or cures available to date, treatments mainly aiming to alleviate the symptoms as and when they appear. Alternate therapeutic approaches are being researched constantly, and there is a growing focus on phytomedicine, herbal medicine, organic compounds, and ayurvedic compounds for the treatment of AD. METHODS: The current study aims to provide an extensive review of these plants against AD from the currently existing literature. Most relevant keywords like Alzheimer's Disease, phytomedicines, ethnic medicines, the role of phytomedicine in neuroprotection, common phytomedicines against AD, etc., were used to select the plants and their metabolites effective in treating AD. The study focuses on six plants: Panax ginseng, Ginkgo biloba, Bacopa monnieri, Withania somnifera, Curcuma longa, and Lavandula angustifolia. Their active components have been studied along with neuroprotective properties, and evidence of in-vitro, pre-clinical, and clinical studies conducted to prove their therapeutic potential against the disease have been presented. RESULTS: All plants envisaged in the study show potential for fighting against AD to varying degrees. Their compounds have shown therapeutic effects by reversing the neurological changes such as clearing Aß plaque and neurofibrillary tangle formation, and ameliorative effects against neurodegeneration through processes including improving concentration, memory, cognition and learning, higher working and cue memory, improved spatial memory, inhibition of NF-κB expression, inhibiting the release of pro-inflammatory cytokines, inhibition of AChE and lipid peroxidase enzymes, and reduction of interleukin levels and tumor necrosis factor-alpha. CONCLUSION: The present review is a comprehensive and up-to-date analysis supported by the evidentiary proofs from pre-clinical studies, meta-analyses, and review papers related to natural phytochemicals' impact on neurodegenerative disorders like AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Idoso , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , NF-kappa B , Fator de Necrose Tumoral alfa , Qualidade de Vida , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Peroxidases/uso terapêutico , Lipídeos
11.
Polymers (Basel) ; 14(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35054731

RESUMO

The novel itraconazole (ITZ) nail penetration enhancing self-emulsifying nanovesicles (ITZ-nPEVs) loaded in carboxymethyl fenugreek gum (CMFG) gel circumvent the systemic onychomycosis treatment. The ITZ-nPEVs were prepared by the thin film hydration technique, and the particle size (PS), zeta potential (ZP), drug content (DC), entrapment efficiency (% EE), deformity index (DI), viscosity, morphology, and physical stability of the ITZ-nPEVs were measured. In terms of nail hydration, transungual drug absorption, and antifungal efficacy against Candida albicans, the chosen ITZ-nPEVs, nPEV-loaded CMFG (CMFG-ITZ-nPEVs) gel, and the commercialized Itrostred gel were compared. The ITZ-nPEVs showed spherical structure with high DC, % EE, low PS and PDI and positive ZP of ITZ ranging from 95.36 to 93.89 mg/5 mL and 95.36-96.94%, 196.55-252.5 nm, 0.092-0.49, and +11.1 to +22.5 mV, respectively. Compared to the Itrostred gel, the novel ITZ-nPEVs exhibited hydration enhancement factor for 24 h (HE24) of 1.53 and 1.39 drug uptake enhancement factor into nail clippings. Moreover, zone of inhibitions for ITZ-nPEVs (27.0 ± 0.25 mm) and CMFG-ITZ-nPEVs (33.2 ± 0.09 mm) against Candida albicans were significantly greater than that of Itrostred gel (22.9 ± 0.44 mm). For clinical investigation on onychomycotic patients, a nail penetration enhancer containing ITZ-nPEV-loaded CMFG gel presents a highly promising approach.

12.
Front Pharmacol ; 12: 717757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489706

RESUMO

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

13.
Molecules ; 27(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35011342

RESUMO

Green synthesis of silver nanoparticles (AgNPs) was synthesized from fresh garlic extract coupled with isoniazid hydrazide (INH), a commonly used antibiotic to treat tuberculosis. A molecular docking study conducted with the selected compounds compared with anthranilate phosphoribosyltransferase (trpD) from Mycobacterium tuberculosis. The aqueous extract of garlic was prepared and mixed with silver nitrate (AgNO3) solution for the superfast synthesis of stable AgNPs. INH was then conjugated with AgNPs at different ratios (v/v) to obtain stable INH-AgNPs conjugates (AgNCs). The resulting AgNCs characterized by FTIR spectra revealed the ultrafast formation of AgNPs (<5 s) and perfectly conjugated with INH. The shifting of λmax to longer wavelength, as found from UV spectral analysis, confirmed the formation of AgNCs, among which ideal formulations (F7, F10, and F13) have been pre-selected. The zeta particle size (PS) and the zeta potential (ZP) of AgNPs were found to be 145.3 ± 2.1 nm and -33.1 mV, respectively. These data were significantly different compared to that of AgNCs (160 ± 2.7 nm and -14.4 mV for F7; 208.9 ± 2.9 nm and -19.8 mV for F10; and 281.3 ± 3.6 nm and -19.5 mV for F13), most probably due to INH conjugation. The results of XRD, SEM and EDX confirmed the formation of AgNCs. From UV spectral analysis, EE of INH as 51.6 ± 5.21, 53.6 ± 6.88, and 70.01 ± 7.11 %, for F7, F10, and F13, respectively. The stability of the three formulations was confirmed in various physiological conditions. Drug was released in a sustainable fashion. Besides, from the preferred 23 compounds, five compounds namely Sativoside R2, Degalactotigonin, Proto-desgalactotigonin, Eruboside B and Sativoside R1 showed a better docking score than trpD, and therefore may help in promoting anti-tubercular activity.


Assuntos
Alho/química , Hidrazinas/química , Isoniazida/síntese química , Isoniazida/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/química , Prata/química , Antituberculosos/química , Antituberculosos/farmacologia , Sítios de Ligação , Técnicas de Química Sintética , Estabilidade de Medicamentos , Química Verde , Isoniazida/química , Ligantes , Nanopartículas Metálicas/ultraestrutura , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Ligação Proteica , Análise Espectral , Relação Estrutura-Atividade
14.
Molecules ; 27(1)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35011465

RESUMO

Inflammation is a natural protective mechanism that occurs when the body's tissue homeostatic mechanisms are disrupted by biotic, physical, or chemical agents. The immune response generates pro-inflammatory mediators, but excessive output, such as chronic inflammation, contributes to many persistent diseases. Some phenolic compounds work in tandem with nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit pro-inflammatory mediators' activity or gene expression, including cyclooxygenase (COX). Various phenolic compounds can also act on transcription factors, such as nuclear factor-κB (NF-κB) or nuclear factor-erythroid factor 2-related factor 2 (Nrf-2), to up-or downregulate elements within the antioxidant response pathways. Phenolic compounds can inhibit enzymes associated with the development of human diseases and have been used to treat various common human ailments, including hypertension, metabolic problems, incendiary infections, and neurodegenerative diseases. The inhibition of the angiotensin-converting enzyme (ACE) by phenolic compounds has been used to treat hypertension. The inhibition of carbohydrate hydrolyzing enzyme represents a type 2 diabetes mellitus therapy, and cholinesterase inhibition has been applied to treat Alzheimer's disease (AD). Phenolic compounds have also demonstrated anti-inflammatory properties to treat skin diseases, rheumatoid arthritis, and inflammatory bowel disease. Plant extracts and phenolic compounds exert protective effects against oxidative stress and inflammation caused by airborne particulate matter, in addition to a range of anti-inflammatory, anticancer, anti-aging, antibacterial, and antiviral activities. Dietary polyphenols have been used to prevent and treat allergy-related diseases. The chemical and biological contributions of phenolic compounds to cardiovascular disease have also been described. This review summarizes the recent progress delineating the multifunctional roles of phenolic compounds, including their anti-inflammatory properties and the molecular pathways through which they exert anti-inflammatory effects on metabolic disorders. This study also discusses current issues and potential prospects for the therapeutic application of phenolic compounds to various human diseases.


Assuntos
Fenóis/química , Fenóis/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Disponibilidade Biológica , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Gerenciamento Clínico , Avaliação Pré-Clínica de Medicamentos , Avaliação do Impacto na Saúde , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Fenóis/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Relação Estrutura-Atividade
15.
Molecules ; 27(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35011482

RESUMO

Plumeria rubra (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of P. rubra in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of P. rubra were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, P. rubra displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. P. rubra has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.


Assuntos
Apocynaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Cardiotônicos/química , Cardiotônicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Coelhos , Vasodilatadores/química , Vasodilatadores/farmacologia
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