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Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N'-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = -8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19.
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FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-ß. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.
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Antineoplásicos , Leucemia Mieloide Aguda , Oxindóis , Tirosina Quinase 3 Semelhante a fms , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Oxindóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Relação Estrutura-AtividadeRESUMO
AIMS: There is a considerable debate on the impact of qat chewing on dental and oral health. Thereby, this study aimed at assessing the dental caries among qat chewers (QC) and non-qat chewers (NQC) who attend outpatient dental clinics, College of Dentistry, Jazan, Saudi Arabia. MATERIALS AND METHODS: A sample of 100 QC and 100 NQC were recruited amongst those attended dental clinics, college of dentistry, Jazan University during the 2018-2019 academic year. Their dental health was assessed by three pre-calibrated male interns using DMFT index. The Care Index, Restorative Index and Treatment Index were calculated. Comparisons between both subgroups were done using independent t test. Multiple linear regression analyses were further conducted to stand on the independent determinants of the oral health among this population. RESULTS: QC were unintentionally older (36.55 ± 8.74 years) than NQC (32.96 ± 8.49 years; P = 0.004). Fifty-six percent of QC reported brushing their teeth compared to only 35% (P = 0.001). NQC with university and postgraduate educational levels were more than QC. The mean Decayed [5.91 (5.16)] and DMFT [9.15 (5.87)] were higher among QC compared to NQC [3.73 (3.62) and 6.7 (4.58); P = 0.001 and 0.001, respectively]. The other indices were not different between both subgroups. The multiple linear regression revealed that qat chewing and age, individually or together, as independent determinants for the dental decay, missing, DMFT and TI. CONCLUSION: Qat chewing habit has a detrimental impact on dental health. It is associated with higher dental caries and missing teeth, and a lower treatment index.
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Cárie Dentária , Humanos , Masculino , Cárie Dentária/epidemiologia , Cárie Dentária/etiologia , Arábia Saudita/epidemiologia , Universidades , MastigaçãoRESUMO
Marine organisms are considered a cache of biologically active metabolites with pharmaceutical, functional, and nutraceutical properties. Among these, marine bioactive peptides (MBAs) present in diverse marine species (fish, sponges, cyanobacteria, fungi, ascidians, seaweeds, & mollusks) have acquired attention owing to their broad-spectrum health-promoting benefits. Nowadays, scientists are keener exploring marine bioactive peptides precisely due to their unique structural and biological properties. These MBAs have reported ameliorating potential against different diseases like hypertension, diabetes, obesity, HIV, cancer, oxidation, and inflammation. Furthermore, MBAs isolated from various marine organisms may also have a beneficial role in the cosmetic, nutraceutical, and food industries. Few marine peptides and their derivative are approved for commercial use, while many MBAs are in various pre-clinical and clinical trials. This review mainly focuses on the diversity of marine bioactive peptides in marine organisms and their production procedures, such as chemical and enzymatic hydrolysis. Moreover, MBAs' therapeutic and biological potential has also been critically discussed herein, along with their status in drug discovery, pre-clinical and clinical trials.
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Organismos Aquáticos , Peptídeos , Animais , Organismos Aquáticos/química , Descoberta de Drogas , Fungos , Humanos , Moluscos , Peptídeos/químicaRESUMO
Over the past decade, the gut microbiota has emerged as an important frontier in understanding the human body's homeostasis and the development of diseases. Gut flora in human beings regulates various metabolic functionalities, including enzymes, amino acid synthesis, bio-transformation of bile acid, fermentation of non-digestible carbohydrates (NDCs), generation of indoles and polyamines (PAs), and production of short-chain fatty acids (SCFAs). Among all the metabolites produced by gut microbiota, SCFAs, the final product of fermentation of dietary fibers by gut microbiota, receive lots of attention from scientists due to their pharmacological and physiological characteristics. However, the molecular mechanisms underlying the role of SCFAs in the interaction between diet, gut microbiota, and host energy metabolism is still needed in-depth research. This review highlights the recent biotechnological advances in applying SCFAs as important metabolites to treat various diseases and maintain colonic health.
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Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Dieta , Fibras na Dieta , Metabolismo Energético/fisiologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , HumanosRESUMO
The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase(Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.
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Molécula L1 de Adesão de Célula Nervosa , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Camundongos , Animais , Feminino , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Fumarato de Quetiapina/farmacologia , Fumarato de Quetiapina/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Mesencéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Fatores de Transcrição/metabolismo , Diferenciação Celular/genética , Trifosfato de Adenosina/metabolismo , Receptores Dopaminérgicos/metabolismoRESUMO
Cancer is the leading cause of death and has remained a big challenge for the scientific community. Because of the growing concerns, new therapeutic regimens are highly demanded to decrease the global burden. Despite advancements in chemotherapy, drug resistance is still a major hurdle to successful treatment. The primary challenge should be identifying and developing appropriate therapeutics for cancer patients to improve their survival. Multiple pathways are dysregulated in cancers, including disturbance in cellular metabolism, cell cycle, apoptosis, or epigenetic alterations. Over the last two decades, natural products have been a major research interest due to their therapeutic potential in various ailments. Natural compounds seem to be an alternative option for cancer management. Natural substances derived from plants and marine sources have been shown to have anti-cancer activity in preclinical settings. They might be proved as a sword to kill cancerous cells. The present review attempted to consolidate the available information on natural compounds derived from plants and marine sources and their anti-cancer potential underlying EMT mechanisms.
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Produtos Biológicos , Neoplasias , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Apoptose , Ciclo CelularRESUMO
Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea (2) was prepared and reacted with various hydrazonoyl halides 3a-h, α-haloketones 5a-d, 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a-h, 3-phenyl-4-arylthiazoles 6a-d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC50 = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.
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Antineoplásicos , Tiadiazóis , Anticonvulsivantes , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Harmina , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Feniltioureia , Piridinas/farmacologia , Relação Estrutura-Atividade , Tiadiazóis/química , Tiazóis/químicaRESUMO
This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.
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Antidepressivos , Depressão , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antioxidantes/farmacologia , Comportamento Animal , Carotenoides , Catalase/farmacologia , Depressão/tratamento farmacológico , Depressão/etiologia , Modelos Animais de Doenças , Glutationa/farmacologia , Camundongos , Estresse Psicológico/tratamento farmacológico , Sacarose/farmacologiaRESUMO
This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.
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Anidrases Carbônicas , Catequina , Plantas Medicinais , Triterpenos , 1-Butanol , Antibacterianos/farmacologia , Antioxidantes/química , Ácido Benzoico , Clorofórmio , Ácidos Graxos , Flavonoides/análise , Flavonoides/farmacologia , Hexanos , Ligantes , Metabolômica , Metanol/química , Simulação de Acoplamento Molecular , Fenóis/análise , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Plantas Medicinais/metabolismo , Estigmasterol , Terpenos , Trientina , Urease , Xantina OxidaseRESUMO
Poor mood, lack of pleasure, reduced focus, remorse, unpleasant thoughts, and sleep difficulties are all symptoms of depression. The only approved treatment for children and adolescents with major depressive disorder (MDD) is fluoxetine hydrochloride (FXN), a serotonin selective reuptake inhibitor antidepressant. MDD is the most common cause of disability worldwide. In the present research, picric acid (PA); dinitrobenzene; p-nitro benzoic acid; 2,6-dichloroquinone-4-chloroimide; 2,6-dibromoquinone-4-chloroimide; and 7,7',8,8'-tetracyanoquinodimethane were used to make 1:1 FXN charge-transfer compounds in solid and liquid forms. The isolated complexes were then characterized by elemental analysis, conductivity, infrared, Raman, and 1H-NMR spectra, thermogravimetric analysis, scanning electron microscopy, and X-ray powder diffraction. Additionally, a molecular docking investigation was conducted on the donor moiety using FXN alone and the resulting charge transfer complex [(FXN)(PA)] as an acceptor to examine the interactions against two protein receptors (serotonin or dopamine). Interestingly, the [(FXN)(PA)] complex binds to both serotonin and dopamine more effectively than the FXN drug alone. Furthermore, [(FXN)(PA)]-serotonin had a greater binding energy than [FXN]-serotonin. Theoretical data were also generated by density functional theory simulations, which aided the molecular geometry investigation and could be beneficial to researchers in the future.
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Transtorno Depressivo Maior , Fluoxetina , Adolescente , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ácido Benzoico , Criança , Transtorno Depressivo Maior/tratamento farmacológico , Dinitrobenzenos , Dopamina/metabolismo , Fluoxetina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Picratos , Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
Haloperidol (HPL) is a typical antipsychotic drug used to treat acute psychotic conditions, delirium, and schizophrenia. Solid charge transfer (CT) products of HPL with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have not been reported till date. Therefore, we conducted this study to investigate the donor-acceptor CT interactions between HPL (donor) and TCNQ and PA (π-acceptors) in liquid and solid states. The complete spectroscopic and analytical analyses deduced that the stoichiometry of these synthesized complexes was 1:1 molar ratio. Molecular docking calculations were performed for HPL as a donor and the resulting CT complexes with TCNQ and PA as acceptors with two protein receptors, serotonin and dopamine, to study the comparative interactions among them, as they are important neurotransmitters that play a large role in mental health. A molecular dynamics simulation was ran for 100 ns with the output from AutoDock Vina to refine docking results and better examine the molecular processes of receptor-ligand interactions. When compared to the reactant donor, the CT complex [(HPL)(TCNQ)] interacted with serotonin and dopamine more efficiently than HPL only. CT complex [(HPL)(TCNQ)] with dopamine (CTtD) showed the greatest binding energy value among all. Additionally, CTtD complex established more a stable interaction with dopamine than HPL-dopamine.
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Antipsicóticos , Haloperidol , Antipsicóticos/farmacologia , Dopamina , Haloperidol/farmacologia , Simulação de Acoplamento Molecular , Nitrilas , Picratos , Receptores DopaminérgicosRESUMO
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.
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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/farmacologiaRESUMO
Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD.
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Células Epiteliais/metabolismo , Deleção de Genes , Metabolômica , Receptores de GABA/genética , Epitélio Pigmentado da Retina/citologia , Linhagem Celular , Análise Discriminante , Células Epiteliais/efeitos dos fármacos , Glucose/metabolismo , Dissulfeto de Glutationa/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , Metaboloma/efeitos dos fármacos , Nucleotídeos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Análise de Componente Principal , Receptores de GABA/metabolismoRESUMO
Crotalaria burhia (Family: Fabaceae) is an important medicinal plant widely distributed in arid parts of the world, including Pakistan, India, and Afghanistan. This plant has enormous ethnobotanical values and is used to treat various common ailments such as swelling, infections, cancer, hydrophobia, pain and skin diseases. Moreover, it is also utilised as food for goats, to make sheds for animals and as a suitable soil binder. This review article is an attempt to analyse critically and to provide updated and categorised information about C. burhia including comprehensive knowledge of the botanical description, traditional/folklore uses, phytochemistry, pharmacological/biological potential, and to facilitate scientific basis for future work. The phytochemical studies (qualitative and quantitative) on C. burhia have indicated the presence of important phytochemical classes, namely alkaloids, flavonoids, glycosides, saponins, phenolics, tannins, steroids, and terpenoids. Pharmacological studies such as anti-inflammatory/analgesic, antioxidant, anti-microbial, anti-tumour, anti-nociceptive, enzyme inhibition, and termiticidal activities were reported from different parts of this plant. Most of the bioassays from this plant have been done on the crude extract. Minimal information about the phytochemicals (responsible for biological activities), except a few compounds has been reported. The potential chemical compounds may need to be purified and tested for the biological potential from isolated compounds in future.
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Clinical multi-drug-resistant bacteria continue to be a serious health problem. Plant-derived molecules are an important source of bioactive compounds to counteract these pathogenic bacteria. In this paper, we studied the chemical composition of the methanol (80%) extract from Pithecellobium dulce seed (Hail, Saudi Arabia) and its ability to inhibit the growth of clinically relevant multi-drug-resistant bacteria. Molecular docking analysis was performed to predict the best compounds with low binding energy and high affinity to interact with two Staphylococcus aureus receptors. Data showed that P. dulce extract is a rich source of D-turanose (55.82%), hexadecanoic acid (11.56%), indole-1-acetic acid (11.42%), inositol (5.78%), and octadecanoic acid (4.36%). The obtained extract showed antibacterial activity towards tested clinical bacterial strains with MIC values ranging from 233 mg/mL for Acinetobacter baumannii to 300 mg/mL for S. aureus and Escherichia coli. Turanose interaction has resulted in -7.4 and -6.6 kcal/mol for 1JIJ and 2XCT macromolecules, while inositol showed energy values (-7.2 and -5.4 kcal/mol) for the same receptors. Multiple identified compounds showed desirable bioavailability properties indicating its great potential therapeutic use in human. Overall, current investigation highlights the possible use of P. dulce extract as a valuable source for drug development against pathogenic drug-resistant bacteria.
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Anti-Infecciosos , Fabaceae , Humanos , Staphylococcus aureus , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , SementesRESUMO
Farnesiferol C (Far-C) is a coumarin commonly extracted from Ferula asafetida and is popularly used as a traditional source of natural remedy. Liver cancer or hepatocellular carcinoma (HCC) has emerged as a major cause behind cancer burden, and limited therapeutic interventions have further aggravated the clinical management of HCC. In the present study, the authors tested the hypothesis that Far-C-instigated oxidative stress resulted in anti-proliferation and apoptosis instigation within human liver cancer HepG2 cells. The observations reported herewith indicated that Far-C exerted considerable cytotoxic effects on HepG2 cells by reducing the cell viability (p < 0.001) in a dose-dependent manner. Far-C exposure also resulted in enhanced ROS production (p < 0.01) which subsequently led to loss of mitochondrial membrane potential. Far-C-instigated oxidative stress also led to enhanced nuclear fragmentation and condensation as revealed through Hoechst-33342. These molecular changes post-Far-C exposure also incited apoptotic cell death which concomitantly led to significant activation of caspase-3 (p < 0.001). Furthermore, Far-C exhibited its competence in altering the expression of genes involved in apoptosis regulation (Bax, Bad, and Bcl2) along with genes exerting regulatory effects on cell cycle (cyclinD1) and its progression (p21Cip1 and CDK4). The evidence thus clearly shows the preclinical efficacy of Far-C against HepG2 cells. However, further mechanistic investigations deciphering the alteration of different pathways post-Far-C exposure will be highly beneficial.
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Cucurbitacin-B (Cur-B) is an analogue triterpenoid belonging to the Cucurbitaceae family. Previous reports have explicitly outlined various biological activities of Cucurbitaceae family members, including the anticancer activity of Cur-B. In the present study, we tried to elucidate the anticancer efficacy of Cur-B against prostate cancer PC3 cells. PC3 cells were exposed to purified Cur-B at 5, 10, 15, 20 and 25 µM for 24. Cur-B exposure reduced cell viability of PC3 cells at 5 µM (p < 0.05), with further reduction with increased Cur-B concentration (15 µM, p < 0.01 and 25 µM, p < 0.001). Cur-B also succeeded in instigating nuclear fragmentation and condensation, followed by activation of caspase-8, -9 and -3 proportionally with increasing concentrations of Cur-B. Treatment with Cur-B also instigated ROS-mediated oxidative stress both qualitatively and quantitatively at 5 µM, p < 0.05; 15 µM, p < 0.01 and 25 µM, p < 0.001. Increased ROS after Cur-B treatment also led to dissipation of mitochondrial membrane potential, thereby resulting in considerable apoptosis (p < 0.001), which, again, was proportionally dependent on Cur-B concentration. Cur-B exposure to PC3 cells was concomitantly followed by reduced cyclin D1, cyclin-dependent kinase 4 (CDK4) expression and augmented mRNA expression of CDK inhibitor p21Cip1. Intriguingly, Cur-B exposure also led to considerable downregulation of the JAK/STAT signaling cascade, which may be the reason behind Cur-B-mediated apoptosis and cell cycle arrest within PC3 cells. Therefore, these observations explicitly establish that Cur-B could serve in the prevention of prostate cancer.
RESUMO
Psychological problems affect a sizable portion of the population, and they require special care. In the current study, we aimed to assess patient satisfaction with the healthcare system at one of the multispecialty hospitals in Riyadh, Saudi Arabia, as well as to identify potential factors that can have an impact on patient satisfaction. A validated pre-tested questionnaire including features to evaluate general hospital services (HS-6 items), nursing services (NS-3 items), pharmacy services (PS-7 items), and a standard patient satisfaction questionnaire (PSQ-18 item) was administered to patients who had been receiving therapy for their psychological disease for the past 3 months. Using binary and multiple regression analysis, the strengths of the associations between sociodemographic factors and patient satisfaction measures were evaluated. The results were expressed as adjusted odds ratios (AOR), which were deemed significant when the P value was < 0.05. Sixty-six percent of the 258 study participants were men, and sixty percent of them were between the ages of 18 and 35 years. The bulk of survey respondents (74%) were employed, married, and well-educated. Our research revealed that those who were employed (AOR, HS-2.5; NS-2.65, PS-2.32), have a higher education (AOR, HS-2.23, NS-2.63, PS-2.82), male gender (AOR, HS-1.12, NS-1.08, PS-1.86) and between the ages of 18 and 35 years (AOR, HS-1.48, NS-1.53, PS-1.67) were more likely to be satisfied with general hospital, nursing, and pharmacy services. Further, those who were married had 1.43 and 1.21 times more chance of satisfaction with the pharmacy and nursing services, respectively, compared to singles. Additionally, those with employment had odds of being satisfied that were 2.4 times higher, highly educated individuals had odds that were 2.1 times higher, participants between the ages of 18 and 35 had odds that were 1.51 times higher, and men had odds that were 1.41 times higher on the patient satisfaction questionnaire scale (PSQ-18). Overall, the study participants' satisfaction with general hospital, nursing, and pharmacy services was 70, 76.3, and 83.3%, respectively, compared to only 61.2% on the PSQ-18. Participants in the survey awarded the hospital amenities, pharmacy services, and nursing care high ratings. The medical care, however, fell short of expectations. The study's findings suggest that action needs to be taken to enhance healthcare system services, particularly in the psychological departments of the medical organization.
Assuntos
Satisfação do Paciente , Satisfação Pessoal , Adolescente , Adulto , Benzoatos , Estudos Transversais , Feminino , Humanos , Masculino , Arábia Saudita , Adulto JovemRESUMO
It is well known that polycystic ovarian syndrome (PCOS) may elevate psychological problems in patients, but there is a scarcity of the studies among Saudi Arabian population. This research was designed to investigate the influence of PCOS on the development of psychological load in terms of depression, anxiety, and stress in comparison to normal women who have no PCOS. Further, a correlation of psychological distress in PCOS females was done with their educational level. This is case-control research carried out in one of Riyadh's multispecialty hospitals. In the PCOS patients and control groups (each with 84 samples), samples were collected using convenience sampling and a simple random approach, respectively. The psychological burden was determined using DASS-21. The data obtained were analyzed using SPSS-IBM 25. Most participants (52.9%) were between the ages of 26 and 35 and had a university education (68.4%). A significantly higher percentage of PCOS patients (P = 0.001) had irregular menses, hirsutism, infertility, and acne in comparison to the mothers without PCOS. There was a significantly higher possibility of depression (P = 0.003), anxiety (P = 0.016), and stress (P = 0.001) among PCOS patients than in control subjects. Among the psychological domain tested in the study, the risk of developing stress (odds ratio, OR = 8.32) was high when compared to depression (OR = 3.12) and anxiety (OR = 2.127) in PCOS patients. Furthermore, when compared to PCOS females with less education, a significantly lower number of university-educated PCOS females developed depression. The study demonstrates a high prevalence of psychological burden among the PCOS population. Higher education has been shown to help in alleviating depression in PCOS females. Meeting PCOS women's psychological needs will improve their overall health status.