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1.
J Pharm Bioallied Sci ; 16(Suppl 2): S1304-S1307, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882735

RESUMO

Objectives: This study presents the antioxidant and anti-inflammatory activity of the ethanolic extract of Euphorbia hirta leaf extract. Materials and Methods: The antioxidant and anti-inflammatory activity of the extract was performed by in vitro assay. Our research employs a comprehensive approach combining experimental assays and computational simulations to assess the extract's potential bioactive components and their interactions with key biomolecules. Results: The study's results demonstrated a progressive rise in the percentage of inhibition, which was dependent on the dosage, in both antioxidant and anti-inflammatory activities. This trend was observed for both the extract and the standard, encompassing concentrations ranging from 100 to 500 µg/ml. Conclusion: The results showed that Euphorbia hirta's possesses antioxidant and anti-inflammatory activity, and this may contribute to a traditional medicinal. The discoveries of this study contribute to a deeper understanding of Euphorbia hirta's medicinal properties and its potential as a source of natural therapeutic agents.

2.
J Pharm Bioallied Sci ; 16(Suppl 2): S1317-S1320, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882754

RESUMO

Tinospora cordifolia, commonly known as "Giloy" or "Guduchi," is a medicinal plant with a rich history in traditional medicine systems. The aqueous extract of Tinospora cordifolia stems has garnered attention due to its reported pharmacological activities. This study aimed to investigate the in vitro biological properties of the aqueous extract and complement the findings with in silico studies to gain insights into potential molecular interactions. The Tinospora cordifolia stem aqueous extract was subjected to a battery of in vitro assays to assess its biological properties. Anti-inflammatory activity was evaluated using invitro assay. To complement the in vitro findings, in silico studies involving molecular docking analyses were conducted to predict potential interactions between the extract's constituents and relevant biomolecular targets. The in vitro evaluation revealed significant anti-inflammatory activity of the Tinospora cordifolia stem aqueous extract, as evidenced by its ability to suppress the production of pro-inflammatory cytokines. In silico studies provided insights into the molecular interactions between the extract's bioactive constituents and key inflammatory and antioxidant targets, further supporting the observed biological properties. The combined in vitro biological assays and in silico studies offer a comprehensive assessment of the Tinospora cordifolia stem aqueous extract's potential therapeutic properties. The demonstrated anti-inflammatory activities align with the traditional use of Tinospora cordifolia and suggest its potential in managing inflammatory and oxidative stress-related disorders. The in silico insights provide a molecular understanding of the extract's mode of action, strengthening the rationale for further investigation and development of natural products derived from Tinospora cordifolia for pharmaceutical and medicinal applications.

3.
J Pharm Bioallied Sci ; 16(Suppl 2): S1308-S1311, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882780

RESUMO

Background: Crataeva nurvala, a medicinal plant with potential therapeutic properties, offers a promising avenue for the development of novel anti-inflammatory drugs. This study adopted a combined in silico and in vitro approach to investigate the anti-inflammatory potential of compounds derived from Crataeva nurvala. Materials and Methods: In the in silico phase, virtual screening and molecular docking analyses were conducted to identify bioactive compounds from Crataeva nurvala that could interact with key inflammatory targets. Subsequently, selected compounds were synthesized and subjected to in vitro experimentation. Cellular models were employed to assess the anti-inflammatory effects of Crataeva nurvala-derived compounds, focusing on the modulation of pro-inflammatory cytokine levels and the underlying signaling pathways. Results: Virtual screening and molecular docking led to the identification of several bioactive compounds with favorable interactions with inflammatory targets. In the in vitro experiments, treatment with Crataeva nurvala-derived compounds resulted in a significant reduction in pro-inflammatory cytokine production. Moreover, the compounds exhibited the ability to modulate inflammatory signaling pathways, further substantiating their anti-inflammatory potential. Conclusions: This study not only contributes to the development of effective anti-inflammatory drugs but also underscores the value of harnessing natural sources such as Crataeva nurvala for therapeutic interventions in inflammatory disorders. The dual-phase strategy presented here provides a robust framework for anti-inflammatory drug discovery and validation.

4.
J Pharm Bioallied Sci ; 16(Suppl 2): S1270-S1273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882817

RESUMO

Sesuvium portulacastrum, a coastal medicinal plant with traditional uses has shown promising biological activities including anti-inflammatory, antioxidant and antimicrobial properties. However, the mechanisms of action active ingredients of this plant have not been studied. Aim of the current study is to investigate the anticancer activity of Sesuvium portulacastrum using in vitro and in silico analysis. The in vitro assays included NO radical scavenging activity, total phenolic and flavonoid content determination. The data were analysed by one-way-ANOVA and p<0.05 was considered as statistically significant. The phytochemical analysis showed the presence of tannins, steroids, terpenoids and phenols. Antioxidant activity of S. portulacastrum showed the dose dependent effect of nitric oxide radical scavenging activity. In silico analysis showed a better binding affinity with IR, IRS1 and Akt molecules which demonstrated the action of bioactive compound of S. portulacastrum against IRS-1/AKT signalling pathway.

5.
J Pharm Bioallied Sci ; 16(Suppl 2): S1312-S1316, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882845

RESUMO

Background: Spermacoce hispida, a medicinal plant from the Rubiaceae family, has garnered attention for its traditional use and reported therapeutic properties. This study aimed to investigate the phytochemical composition and assess the anti-inflammatory and anti-oxidant activities of the ethanolic extract derived from Spermacoce hispida. Materials and Methods: Phytochemical screening of the ethanolic extract involved qualitative analysis to identify major phytoconstituents such as tannins, phenols, and acids. The anti-inflammatory activity was evaluated through in vitro assays, and anti-oxidant potential was assessed using established methods to measure scavenging activity against free radicals and reactive oxygen species. Results: Phytochemical screening revealed the presence of various bioactive constituents in the Spermacoce hispida ethanolic extract, including acid, tannin, protein, and phenolic compounds. Furthermore, the extract exhibited potent anti-oxidant activity, as evidenced by its ability to scavenge free radicals and attenuate ROS-induced oxidative stress. Conclusion: The findings of this study underscore the potential of Spermacoce hispida ethanolic extract as a source of bioactive compounds with anti-inflammatory and anti-oxidant properties. The presence of phytochemicals and the observed bioactivity support its traditional use and suggest potential therapeutic applications. These results contribute to the growing body of knowledge on natural products with health-promoting effects and provide a basis for further research aimed at developing pharmaceutical and medicinal interventions harnessing the benefits of Spermacoce hispida.

6.
J Pharm Bioallied Sci ; 16(Suppl 2): S1246-S1248, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882856

RESUMO

Background: Nowadays, diabetes mellitus has become common worldwide due to changes in lifestyle, sedentary life, alterations in food habits, and other genetic and environmental factors. It is necessary to create awareness about the growing pandemic. Aim: To evaluate the antidiabetic potential of Evolvulus alsinoides. Methods: In vitro α-amylase inhibition and α-glucosidase inhibition activity. Molecular docking analysis. Results: The plant is rich in naturally occurring phytocompound. The results of the study showed that E. alsinoides has the potential to inhibit the activity of alpha-amylase and alpha-glucosidase. Moreover, this result was validated using in silico molecular docking studies that showed a good binding affinity of one of the major phytocompound, caffeic acid, with molecules in the insulin signaling cascade. Conclusion: E. alsinoides has a potent antidiabetic activity and can be further employed in animal and human studies.

7.
J Pharm Bioallied Sci ; 16(Suppl 2): S1291-S1294, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882866

RESUMO

Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3ß, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources.

8.
PLoS Genet ; 20(5): e1011272, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38768219

RESUMO

The position of the nucleus before it divides during mitosis is variable in different budding yeasts. Studies in the pathogenic intron-rich fungus Cryptococcus neoformans reveal that the nucleus moves entirely into the daughter bud before its division. Here, we report functions of a zinc finger motif containing spliceosome protein C. neoformans Slu7 (CnSlu7) in cell cycle progression. The budding yeast and fission yeast homologs of Slu7 have predominant roles for intron 3' splice site definition during pre-mRNA splicing. Using a conditional knockdown strategy, we show CnSlu7 is an essential factor for viability and is required for efficient cell cycle progression with major role during mitosis. Aberrant nuclear migration, including improper positioning of the nucleus as well as the spindle, were frequently observed in cells depleted of CnSlu7. However, cell cycle delays observed due to Slu7 depletion did not activate the Mad2-dependent spindle assembly checkpoint (SAC). Mining of the global transcriptome changes in the Slu7 knockdown strain identified downregulation of transcripts encoding several cell cycle regulators and cytoskeletal factors for nuclear migration, and the splicing of specific introns of these genes was CnSlu7 dependent. To test the importance of splicing activity of CnSlu7 on nuclear migration, we complemented Slu7 knockdown cells with an intron less PAC1 minigene and demonstrated that the nuclear migration defects were significantly rescued. These findings show that CnSlu7 regulates the functions of diverse cell cycle regulators and cytoskeletal components, ensuring timely cell cycle transitions and nuclear division during mitosis.


Assuntos
Núcleo Celular , Cryptococcus neoformans , Proteínas Fúngicas , Mitose , Splicing de RNA , Spliceossomos , Mitose/genética , Cryptococcus neoformans/genética , Splicing de RNA/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Spliceossomos/genética , Spliceossomos/metabolismo , Fuso Acromático/metabolismo , Fuso Acromático/genética , Regulação Fúngica da Expressão Gênica , Ciclo Celular/genética
10.
ACS Appl Mater Interfaces ; 16(21): 27114-27126, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38747624

RESUMO

The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in "always on" photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy.


Assuntos
Glicólise , Sulfeto de Hidrogênio , Irídio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Irídio/química , Irídio/farmacologia , Sulfeto de Hidrogênio/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Glicólise/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Linhagem Celular Tumoral , Fluorescência
11.
Curr Med Chem ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757322

RESUMO

Globally, cardiovascular diseases (CVDs) are the main cause of mortality every year worldwide. CVD health is influenced by various health factors, such as blood pressure, cholesterol levels, and glucose control. The main risk factors include smoking, physical activity, food intake, and body mass index. Around 90% of CVDs could be prevented by controlling these risk factors. Heavy metals are indigenous to the environment of the earth. However, modern lifestyles have led to the exploitation of our environment by unconstrained use of heavy metals. Though heavy metals are essential components, they are hazardous to humans and living systems due to their persistent and non-degradable nature. The mainpurpose of this study is to provide a literature review on the mechanisms of heavy metals, particularly arsenic, lead, and cadmium, that cause cardiovascular diseases. The major mechanism by which heavy metals result in various modalities of cardiovascular disease is the generation of reactive species and the depletionof the antioxidant reserves inside the biological system. The generation of reactive species gradually leads to the activation of various signaling pathways, resulting in either apoptosis or unrestricted cell growth. These unfavorable conditions result in a state when there is an imbalance between reactive species generation and antioxidant activity. Both endogenously present antioxidants and dietary antioxidants are very much essential in regulating the redox potential of the body. They help in the detoxification and excretion of heavy metals and their metabolites in the biological system. Therefore, recognizing the role of heavy metals in cardiovascular health is crucial for developing preventive strategies and interventions aimed at mitigating their adverse effects on human health.

12.
J Orthod Sci ; 13: 14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784082

RESUMO

BACKGROUND: The demand for orthodontic treatment among adults has witnessed a substantial rise in recent years. This study aims to explore the complexities of adult orthodontics, focusing on challenges faced, treatment outcomes, and the influence of factors such as age, gender, and education on patient compliance and satisfaction. METHODS: A multi-dimensional approach was employed, combining a review of clinical records with structured patient surveys. Descriptive statistics summarized demographic characteristics, treatment duration, and orthodontic problems addressed. Inferential statistics included Pearson correlation, Chi-squared tests, and analysis of variance to examine age compliance, gendersatisfaction, and education-orthodontic problem relationships. Qualitative analysis enriched findings, and statistical software facilitated data processing. RESULTS: The analysis revealed a statistically significant negative correlation between age and compliance (r = -0.28, P < 0.05), indicating that younger participants demonstrated higher compliance rates. Gender emerged as a significant factor influencing patient satisfaction (P = 0.024), with females reporting notably higher levels of satisfaction than males. Furthermore, participants with advanced education levels (Master's/Ph.D.) were significantly more likely to have orthodontic issues related to malocclusion (P = 0.041). CONCLUSION: The study provides an insight into the multi-dimensional aspects of adult orthodontics, recognizing the challenges, compliance, and satisfaction levels. Tailored approaches considering age, gender, and education are essential. This research contributes to a deeper understanding of orthodontic treatment in adults and its potential implications for enhanced patient care.

13.
Cell Biochem Funct ; 42(4): e4027, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38715184

RESUMO

Bioactive phytocompounds are crucial components in all plants. Since the time of traditional medicine, the utilization of plants has been grounded in the potential of these bioactive compounds to treat or manage specific illnesses. These natural bioactive compounds have sparked growing interest in employing medicinal plants for addressing various conditions, such as inflammatory diseases, diabetes, and cancer. This study focuses on assessing the qualitative phytochemical composition, antioxidant potential, and cytotoxic effects of blueberry (Vaccinium sect. Cyanococcus) extract using three different solvents, namely water, ethanol, and methanol. The extract exhibited notable antioxidant activities, as evidenced by DPPH and H2O2 free radical scavenging assays. The cell viability assay also demonstrated cell growth inhibition in A549 cells. Furthermore, nine specific phytocompounds sourced from existing literature were selected for molecular docking studies against CDK6 and, AMPK key protein kinases which enhance the cancer progression. The molecular docking results also revealed favorable binding scores, with a high score of -9.5 kcal/mol in CDK6 protein and a maximum score of AMPK with targets of -8.8 kcal/mol. The selected phytocompounds' pharmacodynamic properties such as ADMET also supported the study. Furthermore, rutin stated that pre-dominantly present in blueberry plants shows a potent cytotoxicity effect in A549 cells. Functional annotations by bioinformatic analysis for rutin also revealed the strong enrichment in the involvement of PI3K/AKT1/STAT, and p53 signaling pathways. Based on this analysis, the identified rutin and other compounds hold a promising anticancer activity. Overall, the comprehensive evaluation of both in vitro and in silico data suggests that the Vaccinium sect. Cyanococcus extract could serve as a valuable source of pharmaceutical agents and may prove effective in future therapeutic applications.


Assuntos
Mirtilos Azuis (Planta) , Proliferação de Células , Receptores ErbB , Estresse Oxidativo , Extratos Vegetais , Fator de Transcrição STAT3 , Transdução de Sinais , Proteína Supressora de Tumor p53 , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Mirtilos Azuis (Planta)/química , Estresse Oxidativo/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Células A549 , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Interleucina-6/metabolismo , Simulação de Acoplamento Molecular , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Sobrevivência Celular/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais
14.
J Stomatol Oral Maxillofac Surg ; : 101909, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729427

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) poses a significant healthcare challenge globally, necessitating precise biomarkers for effective management. Interleukin-6 (IL-6) in saliva has emerged as a potential biomarker, yet its dynamics post-chemotherapy and radiotherapy remain underexplored. AIM: The aim of our study is to investigate the longitudinal dynamics of salivary interleukin-6 (IL-6) expression in postoperative OSCC patients over a one-year follow-up period after chemotherapy and radiotherapy. METHODS: This longitudinal study enrolled 60 participants, including postoperative OSCC patients and controls, collecting saliva samples over one year. RT-PCR and ELISA techniques measured IL-6 expression. Statistical analyses, including repeated measures ANOVA and univariate tests, evaluated IL-6 dynamics. RESULTS: Pre-treatment, OSCC patients exhibited elevated IL-6 levels compared to controls. Post-therapy, IL-6 levels decreased significantly with p < .0001, indicating treatment response and further result to baseline normalizing at 6-month follow-up. Significant differences were observed across treatment stages, supporting IL-6 as a diagnostic and prognostic marker for OSCC. RT-PCR and ELISA results showed the statistical significance of IL-6's role as a predictive marker. CONCLUSION: Salivary IL-6 emerges as a promising biomarker in OSCC management, necessitating further research to harness its diagnostic and therapeutic potential. By understanding IL-6 dynamics, personalized treatment approaches can be developed to improve patient outcomes. Longitudinal studies with larger cohorts and multi-omics approaches are warranted to validate findings and identify novel therapeutic targets.

15.
Food Nutr Res ; 682024.
Artigo em Inglês | MEDLINE | ID: mdl-38571915

RESUMO

Background: Nimbolide, a bioactive compound derived from the neem tree, has garnered attention as a potential breakthrough in the prevention and treatment of chronic diseases. Recent updates in research highlight its multifaceted pharmacological properties, demonstrating anti-inflammatory, antioxidant, and anticancer effects. With a rich history in traditional medicine, nimbolide efficacy in addressing the molecular complexities of conditions such as cardiovascular diseases, diabetes, and cancer positions it as a promising candidate for further exploration. As studies progress, the recent update underscores the growing optimism surrounding nimbolide as a valuable tool in the ongoing pursuit of innovative therapeutic strategies for chronic diseases. Methods: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Results: Most studies have shown the Nimbolide is one of the most potent limonoids derived from the flowers and leaves of neem (Azadirachta indica), which is widely used to treat a variety of human diseases. In chronic diseases, nimbolide reported to modulate the key signaling pathways, such as Mitogen-activated protein kinases (MAPKs), Wingless-related integration site-ß (Wnt-ß)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-ß), Matrix metalloproteinases (MMPs), Vascular Endothelial Growth Factor (VEGF), inflammatory cytokines, and epithelial-mesenchymal transition (EMT) proteins. Nimbolide has anti-inflammatory, anti-microbial, and anti-cancer properties, which make it an intriguing compound for research. Nimbolide demonstrated therapeutic potential for osteoarthritis, rheumatoid arthritis, cardiovascular, inflammation and cancer. Conclusion: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

17.
Acta Trop ; 255: 107216, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38636584

RESUMO

According to the World Health Organization, infectious diseases, particularly those caused by multidrug-resistant bacteria (MDR), are projected to claim the lives of 15 million people by 2050. Septicemia carries a higher morbidity and mortality rate than infections caused by susceptible Pseudomonas aeruginosa, and MDR-mediated ocular infections can lead to impaired vision and blindness. To identify and develop a potential drug against MDR P. aeruginosa, we employed in silico reverse genetics-based target mining, drug prioritization, and evaluation. Rare Lipoprotein A (RlpA) was selected as the target protein, and its crystal structure was geometrically optimized. Molecular docking and virtual screening analyses revealed that RlpA exhibits strong binding affinity with 11 compounds. Among these, 3-chlorophthalic acid was evaluated, and subsequent in vitro assays demonstrated significant anti-Pseudomonas activity with negligible cytotoxicity. The compound was further evaluated against both drug-susceptible and MDR P. aeruginosa strains in vitro, with cytotoxicity assessed using an MTT assay. The study demonstrated that 3-chlorophthalic acid exhibits potent anti-Pseudomonas activity with minimal toxicity to host cells. Consequently, this compound emerges as a promising candidate against MDR P. aeruginosa, warranting further investigation.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Lipoproteínas/farmacologia , Lipoproteínas/genética , Lipoproteínas/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia
18.
Cureus ; 16(2): e53458, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38435153

RESUMO

Background Oral carcinoma presents a significant health challenge, prompting the need for innovative therapeutic approaches. Elevation of inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), has promoted cellular proliferation, inhibited apoptosis, and fostered oral cancer progression through complex signaling pathways. Hesperidin, a flavanone glycoside found in citrus fruits, is of keen interest in this study as it has been proven to have multiple health benefits through in vivo and in vitro studies. However, the mechanism behind the anticancer activity of hesperidin in oral carcinoma remains obscure. Aim The study aimed to explore the anticancer potential of hesperidin on human oral cancer cells (KB cells) by modulating pro-inflammatory and apoptotic signaling mechanisms. Methods Cancer cell growth inhibitory activity was assessed using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Gene expression analysis was performed using real-time RT-PCR analysis. In addition, in silico docking analysis was conducted to confirm the binding affinity of hesperidin with pro-inflammatory and apoptosis signaling molecules. The data were analyzed using one-way ANOVA and the "t" test. Results Utilizing the MTT assay, a dose-dependent cytotoxic effect of hesperidin was unveiled, with a remarkable IC50 value indicative of its potent inhibition of cell proliferation. Complementing these findings (p<0.05), qRT-PCR analysis demonstrated hesperidin's regulatory influence on key molecular targets within the KB cell line. Hesperidin treatment resulted in a noteworthy reduction in TNF-α, interleukin-1 beta (IL-1-ß), IL-6, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and B-cell lymphoma 2 (Bcl-2) mRNA expression levels (p<0.05), highlighting its inhibitory role in cell proliferation, migration, and inflammation processes. Simultaneously, hesperidin promoted the expression of BAX mRNA (p<0.05), indicating an enhancement in cell death. Molecular docking simulations further revealed robust binding affinities between hesperidin and target proteins, suggesting its potential to disrupt cellular functions and inflammatory signaling pathways in oral cancer cells. Conclusion The cytotoxic effects on the KB cell line and its anti-inflammatory properties position hesperidin as a compelling candidate for further exploration in the quest for effective oral carcinoma treatments. These findings shed light on the intricate molecular mechanisms underlying hesperidin's promise as a therapeutic agent against oral carcinoma.

19.
Aging (Albany NY) ; 16(6): 5000-5026, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38517361

RESUMO

D-galactose (D-gal) administration was proven to induce cognitive impairment and aging in rodents' models. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes. GNL reduces inflammation by changing important signaling pathways and cytokines, and thus it is plausible to be used as a medicine for treating disorders linked to inflammation. Herein, we examined the therapeutic effects of GNL on D-gal-induced oxidative stress and neuroinflammation-mediated memory loss in mice. The study was conducted using six groups of mice (6 mice per group). The first group received normal saline, then D-gal (150 mg/wt) dissolved in normal saline solution (0.9%, w/v) was given orally for 9 weeks to the second group. In the III group, from the second week until the 10th week, mice were treated orally (without anesthesia) with D-gal (150 mg/kg body wt) and GNL weekly twice (40 mg/kg body wt) four hours later. Mice in Group IV were treated with GNL from the second week up until the end of the experiment. For comparison of young versus elderly mice, 4 month old (Group V) and 16-month-old (Group VI) control mice were used. We evaluated the changes in antioxidant levels, PI3K/Akt levels, and Nrf2 levels. We also examined how D-gal and GNL treated pathological aging changes. Administration of GNL induced a significant increase in spatial learning and memory with spontaneously altered behavior. Enhancing anti-oxidant and anti-inflammatory effects and activating PI3K/Akt were the mechanisms that mediated this effect. Further, GNL treatment upregulated Nrf2 and HO-1 to reduce oxidative stress and apoptosis. This was confirmed using 99mTc-HMPAO brain flow gamma bioassays. Thus, our data suggested GNL as a promising agent for treating neuroinflammation-induced cognitive impairment.


Assuntos
Monoterpenos Acíclicos , Disfunção Cognitiva , Galactose , Humanos , Camundongos , Animais , Galactose/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doenças Neuroinflamatórias , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Estresse Oxidativo , Envelhecimento/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Antioxidantes/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico
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