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1.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000469

RESUMO

Coronavirus can cause various diseases, from mild symptoms to the recent severe COVID-19. The coronavirus RNA genome is frequently mutated due to its RNA nature, resulting in many pathogenic and drug-resistant variants. Therefore, many medicines should be prepared to respond to the various coronavirus variants. In this report, we demonstrated that Forsythia viridissima fruit ethanol extract (FVFE) effectively reduces coronavirus replication. We attempted to identify the active compounds and found that actigenin from FVFE effectively reduces human coronavirus replication. Arctigenin treatment can reduce coronavirus protein expression and coronavirus-induced cytotoxicity. These results collectively suggest that arctigenin is a potent natural compound that prevents coronavirus replication.


Assuntos
Forsythia , Frutas , Furanos , Lignanas , Extratos Vegetais , Replicação Viral , Forsythia/química , Lignanas/farmacologia , Replicação Viral/efeitos dos fármacos , Furanos/farmacologia , Humanos , Frutas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Antivirais/farmacologia , Antivirais/química , Animais , Chlorocebus aethiops , Células Vero
2.
PeerJ ; 12: e17532, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873643

RESUMO

Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. Phenethyl isothiocyanate (PEITC) is a bioactive substance present primarily in the cruciferous vegetables. PEITC has exhibited anti-cancer properties in various cancers, including lung, bile duct, and prostate cancers. It has been demonstrated that PEITC can inhibit the proliferation, invasion, and metastasis of SK-Hep1 cells, while effectively inducing apoptosis and cell cycle arrest in HepG2 cells. However, knowledge of its anti-carcinogenic effects on Huh7.5.1 cells and its underlying mechanism remains elusive. In the present study, we aim to evaluate the anti-carcinogenic effects of PEITC on human HCC Huh7.5.1 cells. Methods: MTT assay and colony formation assay was performed to investigate the anti-proliferative effects of PEITC against Huh7.5.1 cells. The pro-apoptosis effects of PEITC were determined by Annexin V-FITC/PI double staining assay by flow cytometry (FCM), mitochondrial transmembrane potential (MMP) measurement, and Caspase-3 activity detection. A DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was conducted to estimate the DNA damage in Huh7.5.1 cells induced by PEITC. Cell cycle progression was determined by FCM. Transwell invasion assay and wound healing migration assay were performed to investigate the impact of PEITC on the migration and invasion of Huh7.5.1 cells. In addition, transcriptome sequencing and gene set enrichment analysis (GSEA) were used to explore the potential molecular mechanisms of the inhibitory effects of PEITC on HCC. Quantitative real-time PCR (qRT-PCR) analysis was performed to verify the transcriptome data. Results: MTT assay showed that treatment of Huh7.5.1 cells with PEITC resulted in a dose-dependent decrease in viability, and colony formation assay further confirmed its anti-proliferative effect. Furthermore, we found that PEITC could induce mitochondrial-related apoptotic responses, including a decrease of mitochondrial transmembrane potential, activation of Caspase-3 activity, and generation of intracellular reactive oxygen species. It was also observed that PEITC caused DNA damage and cell cycle arrest in the S-phase in Huh7.5.1 cells. In addition, the inhibitory effect of PEITC on the migration and invasion ability of Huh7.5.1 cells was assessed. Transcriptome sequencing analysis further suggested that PEITC could activate the typical MAPK, PI3K-Akt, and p53 signaling pathways, revealing the potential mechanism of PEITC in inhibiting the carcinogenic properties of Huh7.5.1 cells. Conclusion: PEITC exhibits anti-carcinogenic activities against human HCC Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways. Our results suggest that PEITC may be useful for the anti-HCC treatment.


Assuntos
Apoptose , Carcinoma Hepatocelular , Proliferação de Células , Isotiocianatos , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética
3.
Mar Drugs ; 22(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38921571

RESUMO

TRAF6 is an E3 ubiquitin ligase that plays a crucial role in cell signaling. It is known that MMP is involved in tumor metastasis, and TRAF6 induces MMP-9 expression by binding to BSG. However, inhibiting TRAF6's ubiquitinase activity without disrupting the RING domain is a challenge that requires further research. To address this, we conducted computer-based drug screening to identify potential TRAF6 inhibitors. Using a ligand-receptor complex pharmacophore based on the inhibitor EGCG, known for its anti-tumor properties, we screened 52,765 marine compounds. After the molecular docking of 405 molecules with TRAF6, six compounds were selected for further analysis. By replacing fragments of non-binding compounds and conducting second docking, we identified two promising molecules, CMNPD9212-16 and CMNPD12791-8, with strong binding activity and favorable pharmacological properties. ADME and toxicity predictions confirmed their potential as TRAF6 inhibitors. Molecular dynamics simulations showed that CMNPD12791-8 maintained a stable structure with the target protein, comparable to EGCG. Therefore, CMNPD12791-8 holds promise as a potential inhibitor of TRAF6 for inhibiting tumor growth and metastasis.


Assuntos
Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fator 6 Associado a Receptor de TNF , Humanos , Fator 6 Associado a Receptor de TNF/antagonistas & inibidores , Fator 6 Associado a Receptor de TNF/metabolismo , Organismos Aquáticos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Avaliação Pré-Clínica de Medicamentos/métodos , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/química , Farmacóforo , Peptídeos e Proteínas de Sinalização Intracelular
4.
Inflammopharmacology ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907857

RESUMO

Burns are a global health problem and can be caused by several factors, including ultraviolet (UV) radiation. Exposure to UVB radiation can cause sunburn and a consequent inflammatory response characterised by pain, oedema, inflammatory cell infiltration, and erythema. Pharmacological treatments available to treat burns and the pain caused by them include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antimicrobials and glucocorticoids, which are associated with adverse effects. Therefore, the search for new therapeutic alternatives is needed. Diosmetin, an aglycone of the flavonoid diosmin, has antinociceptive, antioxidant and anti-inflammatory properties. Thus, we evaluated the antinociceptive and anti-inflammatory effects of topical diosmetin (0.01, 0.1 and 1%) in a UVB radiation-induced sunburn model in mice. The right hind paw of the anaesthetised mice was exposed only once to UVB radiation (0.75 J/cm2) and immediately treated with diosmetin once a day for 5 days. The diosmetin antinociceptive effect was evaluated by mechanical allodynia and pain affective-motivational behaviour, while its anti-inflammatory activity was assessed by measuring paw oedema and polymorphonuclear cell infiltration. Mice exposed to UVB radiation presented mechanical allodynia, increased pain affective-motivational behaviour, paw oedema and polymorphonuclear cell infiltration into the paw tissue. Topical Pemulen® TR2 1% diosmetin reduced the mechanical allodynia, the pain affective-motivational behaviour, the paw oedema and the number of polymorphonuclear cells in the mice's paw tissue similar to that presented by Pemulen® TR2 0.1% dexamethasone. These findings indicate that diosmetin has therapeutic potential and may be a promising strategy for treating patients experiencing inflammatory pain, especially those associated with sunburn.

5.
Food Environ Virol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884930

RESUMO

Gastroenteritis and hepatitis are the most common illnesses resulting from the consumption of food contaminated with human enteric viruses. Several natural compounds have demonstrated antiviral activity against human enteric viruses, such as human norovirus and hepatitis A virus, while little information is available for hepatitis E virus. Many in-vitro studies have evaluated the efficacy of different natural compounds against human enteric viruses or their surrogates. However, only few studies have investigated their antiviral activity in food applications. Among them, green tea extract, grape seed extract and carrageenans have been extensively investigated as antiviral natural compounds to improve food safety. Indeed, these extracts have been studied as sanitizers on food-contact surfaces, in produce washing solutions, as active fractions in antiviral food-packaging materials, and in edible coatings. The most innovative applications of these antiviral natural extracts include the development of coatings to extend the shelf life of berries or their combination with established food technologies for improved processes. This review summarizes existing knowledge in the underexplored field of natural compounds for enhancing the safety of viral-contaminated foods and underscores the research needs to be covered in the near future.

6.
Int J Antimicrob Agents ; 64(2): 107243, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908533

RESUMO

Polymicrobial biofilms are among the leading causes of antimicrobial treatment failure. In these biofilms, bacterial and fungal pathogens interact synergistically at the interspecies, intraspecies, and interkingdom levels. Consequently, combating polymicrobial biofilms is substantially more difficult compared to single-species biofilms due to their distinct properties and the resulting potential variation in antimicrobial drug efficiency. In recent years, there has been an increased focus on developing alternative strategies for controlling polymicrobial biofilms formed by bacterial and fungal pathogens. Current approaches for controlling polymicrobial biofilms include monotherapy (using either natural or synthetic compounds), combination treatments, and nanomaterials. Here, a comprehensive review of different types of polymicrobial interactions between pathogenic bacterial species or bacteria and fungi is provided along with a discussion of their relevance. The mechanisms of action of individual compounds, combination treatments, and nanomaterials against polymicrobial biofilms are thoroughly explored. This review provides various future perspectives that can advance the strategies used to control polymicrobial biofilms and their likely modes of action. Since the majority of research on combating polymicrobial biofilms has been conducted in vitro, it would be an essential step in performing in vivo tests to determine the clinical effectiveness of different treatments against polymicrobial biofilms.

7.
Front Pharmacol ; 15: 1409506, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855749

RESUMO

Introduction: Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms. Methods: We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity. Results: Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models. Conclusion: Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

8.
Drug Des Devel Ther ; 18: 1947-1968, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831870

RESUMO

In an era where synthetic supplements have raised concerns regarding their effects on human health, Ficus carica has emerged as a natural alternative rich in polyphenolic compounds with potent therapeutic properties. Various studies on F. carica focusing on the analysis and validation of its pharmacological and nutritional properties are emerging. This paper summarizes present data and information on the phytochemical, nutritional values, therapeutic potential, as well as the toxicity profile of F. carica. An extensive search was conducted from various databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. A total of 126 studies and articles related to F. carica that were published between 1999 and 2023 were included in this review. Remarkably, F. carica exhibits a diverse array of advantageous effects, including, but not limited to, antioxidant, anti-neurodegenerative, antimicrobial, antiviral, anti-inflammatory, anti-arthritic, antiepileptic, anticonvulsant, anti-hyperlipidemic, anti-angiogenic, antidiabetic, anti-cancer, and antimutagenic properties. Among the highlights include that antioxidants from F. carica were demonstrated to inhibit cholinesterase, potentially protecting neurons in Alzheimer's disease and other neurodegenerative conditions. The antimicrobial activities of F. carica were attributed to its high flavonoids and terpenoids content, while its virucidal action through the inhibition of DNA and RNA replication was postulated due to its triterpenes content. Inflammatory and arthritic conditions may also benefit from its anti-inflammatory and anti-arthritic properties through the modulation of various signalling proteins. Studies have also shown that F. carica extracts were generally safe and exhibit low toxicity profile, although more research in this aspect is required, specifically its effects on the skin. In conclusion, this study highlights the potential of F. carica as a valuable natural therapeutic agent and dietary supplement. However, continued exploration on F. carica's safety and efficacy is still required prior to embarking on clinical trials, as its role in personalized nutrition and medication will open a new paradigm to improve health outcomes.


Assuntos
Suplementos Nutricionais , Ficus , Ficus/química , Humanos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
9.
Food Sci Nutr ; 12(5): 3046-3067, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726411

RESUMO

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

10.
Heliyon ; 10(9): e29976, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765107

RESUMO

Sinomenine (SIN), an alkaloid derived from the traditional Chinese medicine, Caulis Sinomenii, has been used as an anti-inflammatory drug in China for over 30 years. With the continuous increase in research on the pharmacological mechanism of SIN, it has been found that, in addition to the typical rheumatoid arthritis (RA) treatment, SIN can be used as a potentially effective therapeutic drug for anti-tumour, anti-renal, and anti-nervous system diseases. By reviewing a large amount of literature and conducting a summary analysis of the literature pertaining to the pharmacological mechanism of SIN, we completed a review that focused on SIN, found that the current research is insufficient, and offered an outlook for future SIN development. We hope that this review will increase the public understanding of the pharmacological mechanisms of SIN, discover SIN research trial shortcomings, and promote the effective treatment of immune diseases, inflammation, and other related diseases.

11.
Int J Bipolar Disord ; 12(1): 16, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722415

RESUMO

BACKGROUND: Red onion husk, a readily available agricultural waste material, contains diverse bioactive compounds with potential health benefits. This study aimed to assess the safety and therapeutic potential of red onion husk extract in managing manic-like symptoms and associated neurochemical dysfunctions. METHODS: Acute and repeated oral dose studies were conducted in mice and rats to evaluate the safety profile of the extract. FT-IR analysis identified functional groups in the extract, while GC-MS analysis identified specific bioactive compounds in the flavonoid-rich fraction. A ketamine-induced manic behaviour model in Wistar rats was employed to assess the extract's efficacy in attenuating manic-like symptoms. Behavioural and neurochemical analyses were performed to further investigate the extract's effects. RESULTS: The extract demonstrated a favourable safety profile in both acute and repeated dose studies. FT-IR analysis revealed a complex mixture of organic compounds, including hydroxyl groups, alkynes/nitriles, aromatic and non-aromatic C = C bonds, amines, and polysaccharides. GC-MS analysis identified 17 bioactive compounds, including five-methyl-2-phenylindolizine, methadone N-oxide, and 3-phenylthiane, S-oxide. Ketamine administration significantly increased oxidative stress markers, TBARS, and suppressed antioxidant enzyme activities (SOD, GPx, CAT) in both the cerebral cortex and hippocampus, alongside elevated acetylcholinesterase (AchE) activity, indicating enhanced neuronal excitability. Pre-treatment with FRF (25 mg/kg) effectively mitigated ketamine-induced oxidative stress, as evidenced by reduced TBARS levels and partially restored SOD and GPx activities. Interestingly, FRF significantly increased CAT activity (p < 0.001), potentially suggesting an additional compensatory mechanism. Notably, FRF pre-treatment also counteracted ketamine-upregulated AchE activity, offering neuroprotection against heightened neuronal excitability. CONCLUSION: Red onion husk extract exhibits a favourable safety profile and exerts potent antioxidant and neuroprotective effects, possibly through modulating Nrf2 signalling pathways. Its ability to counteract ketamine-induced oxidative stress and neuronal hyperactivity highlights its potential as a complementary therapeutic strategy for managing manic episodes in bipolar disorder. Further research is warranted to elucidate the precise molecular mechanisms underlying FRF's action and explore its clinical efficacy in human studies.

12.
Neurochem Int ; 177: 105762, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723901

RESUMO

Linalool is a neuroprotective monoterpene found in essential oils from aromatic plants. Linalool's effectiveness in AD animal models has been established previously, but its mechanisms of action remain unclear. Therefore, this study aims to investigate whether linalool binds directly to the amyloid beta (Aß) fibrils to understand it's role in preventing neurodegeneration. The anti-aggregation ability of Linalool was determined using Dithiothreitol (DTT), and thermal aggregation assays followed by Thioflavin T (ThT) binding assay. AD animals were treated with Linalool, and Thioflavin T staining was used to check the binding of linalool to Aß fibrils in rat brain tissue sections. Preliminary studies revealed the anti-aggregation potential of linalool under the thermal and chemical stimulus. Further, in ThT binding assay Linalool inhibited Aß aggregation, binding directly to Aß fibrils. The reduced fluorescence intensity of ThT in AD brain tissues following linalool administration, highlights its neuroprotective potential as a therapeutic agent for AD.


Assuntos
Monoterpenos Acíclicos , Peptídeos beta-Amiloides , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Monoterpenos Acíclicos/farmacologia , Animais , Ratos , Masculino , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Monoterpenos/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Fármacos Neuroprotetores/farmacologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Ratos Wistar , Agregados Proteicos/efeitos dos fármacos , Agregados Proteicos/fisiologia , Ratos Sprague-Dawley , Agregação Patológica de Proteínas/tratamento farmacológico , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/prevenção & controle
13.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732127

RESUMO

The process of adipocyte browning has recently emerged as a novel therapeutic target for combating obesity and obesity-related diseases. Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated via brown adipose tissue (BAT). The recruitment and activation of BAT can be induced through chemical drugs and nutrients, with subsequent beneficial health effects through the utilization of carbohydrates and fats to generate heat to maintain body temperature. However, since potent drugs may show adverse side effects, nutritional or natural substances could be safe and effective as potential adipocyte browning agents. This review aims to provide an extensive overview of the natural food compounds that have been shown to activate brown adipocytes in humans, animals, and in cultured cells. In addition, some key genetic and molecular targets and the mechanisms of action of these natural compounds reported to have therapeutic potential to combat obesity are discussed.


Assuntos
Tecido Adiposo Marrom , Produtos Biológicos , Obesidade , Termogênese , Termogênese/efeitos dos fármacos , Humanos , Animais , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Adipócitos Marrons/metabolismo , Adipócitos Marrons/efeitos dos fármacos
14.
MethodsX ; 12: 102743, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38799035

RESUMO

The Caenorhabditis elegans egg hatching methodology is a valuable tool for assessing the anthelmintic activity of drugs and compounds and evaluating anthelmintic drug efficacy. Isolated eggs from gravid adults are exposed to different concentrations of selected drugs and the percentage of egg hatching is determined with respect to the control condition. The assay allows the construction of concentration-response curves and determination of EC50 or EC90 values for egg hatching inhibition. Also, it allows measurements of inhibition as a function of time of exposure. This approach addresses the urgent need for new anthelmintics, as resistance to current treatments poses a significant challenge in parasitic nematode infection. This resistance not only affects humans but also animals and plants, causing significant economic losses in livestock farming and agriculture. By using the free-living nematode C. elegans as a parasitic model organism, researchers can efficiently screen for potential treatments and assess drug combinations for synergistic effects. Importantly, this assay offers a cost-effective and accessible alternative to traditional methods, eliminating the need for specialized infrastructure, hosts, and trained animal maintenance personnel. Additionally, the methodology closely mimics natural conditions, providing insights into egg development and potential therapeutic targets. This method allows for evaluating the direct negative impact of drugs on egg hatching, which correlates with long-term anthelmintic effects, offering advantages in preventing or reducing the transmission and spread of worm infections by eggs. Overall, this approach represents a significant advancement for anthelmintic discovery, offering both practical applications and avenues for further scientific research. •The C. elegans egg hatching assay is a robust and effective method for assessing the anthelmintic potential of various drugs and compounds, allowing the generation of concentration-response curves.•By leveraging the free-living nematode C. elegans as a parasitic model organism, this method facilitates efficient screening of potential treatments and evaluation of drug combinations.•The method addresses the urgent need for new anthelmintics, offering a cost-effective and accessible alternative to traditional approaches.

15.
J Pharm Anal ; 14(5): 100923, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799232

RESUMO

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen "green" natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

16.
J Toxicol Environ Health A ; 87(11): 457-470, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38576186

RESUMO

Glutamate is one of the predominant excitatory neurotransmitters released from the central nervous system; however, at high concentrations, this substance may induce excitotoxicity. This phenomenon is involved in numerous neuropathologies. At present, clinically available pharmacotherapeutic agents to counteract glutamatergic excitotoxicity are not completely effective; therefore, research to develop novel compounds is necessary. In this study, the main objective was to determine the pharmacotherapeutic potential of the hydroalcoholic extract of Psidium guajava (PG) in a model of oxidative stress-induced by exposure to glutamate utilizing Danio rerio larvae (zebrafish) as a model. Data showed that treatment with glutamate produced a significant increase in oxidative stress, chromatin damage, apoptosis, and locomotor dysfunction. All these effects were attenuated by pre-treatment with the classical antioxidant N-acetylcysteine (NAC). Treatment with PG inhibited oxidative stress responsible for cellular damage induced by glutamate. However, exposure to PG failed to prevent glutamate-initiated locomotor damage. Our findings suggest that under conditions of oxidative stress, PG can be considered as a promising candidate for treatment of glutamatergic excitotoxicity and consequent neurodegenerative diseases.


Assuntos
Psidium , Peixe-Zebra , Animais , Glutamatos/toxicidade , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta
17.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674064

RESUMO

Olive leaf contains plenty of phenolic compounds, among which oleuropein (OP) is the main component and belongs to the group of secoiridoids. Additionally, phenolic compounds such as oleocanthal (OL) and oleacein (OC), which share a structural similarity with OP and two aldehyde groups, are also present in olive leaves. These compounds have been studied for several health benefits, such as anti-cancer and antioxidant effects. However, their impact on the skin remains unknown. Therefore, this study aims to compare the effects of these three compounds on melanogenesis using B16F10 cells and human epidermal cells. Thousands of gene expressions were measured by global gene expression profiling with B16F10 cells. We found that glutaraldehyde compounds derived from olive leaves have a potential effect on the activation of the melanogenesis pathway and inducing differentiation in B16F10 cells. Accordingly, the pro-melanogenesis effect was investigated by means of melanin quantification, mRNA, and protein expression using human epidermal melanocytes (HEM). This study suggests that secoiridoid and its derivates have an impact on skin protection by promoting melanin production in both human and mouse cell lines.


Assuntos
Glucosídeos Iridoides , Melaninas , Melanócitos , Olea , Fenóis , Humanos , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Olea/química , Animais , Melaninas/biossíntese , Melaninas/metabolismo , Camundongos , Fenóis/farmacologia , Glucosídeos Iridoides/farmacologia , Iridoides/farmacologia , Aldeídos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Monoterpenos Ciclopentânicos , Células Epidérmicas/metabolismo , Células Epidérmicas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Epiderme/metabolismo , Epiderme/efeitos dos fármacos , Linhagem Celular Tumoral , Folhas de Planta/química , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Melanogênese
18.
Parasitol Res ; 123(4): 185, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632113

RESUMO

Leishmania braziliensis (L. braziliensis) causes cutaneous leishmaniasis (CL) in the New World. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administer. Topical treatment would be the ideal option for the treatment of CL. This underscores the urgent need for affordable and effective treatments, with natural compounds being explored as potential solutions. The alkaloid piperine (PIP), the polyphenol curcumin (CUR), and the flavonoid quercetin (QUE), known for their diverse biological properties, are promising candidates to address these parasitic diseases. Initially, the in vitro cytotoxicity activity of the compounds was evaluated using U-937 cells, followed by the assessment of the leishmanicidal activity of these compounds against amastigotes of L. braziliensis. Subsequently, a golden hamster model with stationary-phase L. braziliensis promastigote infections was employed. Once the ulcer appeared, hamsters were treated with QUE, PIP, or CUR formulations and compared to the control group treated with meglumine antimoniate administered intralesionally. We observed that the three organic compounds showed high in vitro leishmanicidal activity with effective concentrations of less than 50 mM, with PIP having the highest activity at a concentration of 8 mM. None of the compounds showed cytotoxic activity for U937 macrophages with values between 500 and 700 mM. In vivo, topical treatment with QUE daily for 15 days produced cured in 100% of hamsters while the effectiveness of CUR and PIP was 83% and 67%, respectively. No failures were observed with QUE. Collectively, our data suggest that topical formulations mainly for QUE but also for CUR and PIP could be a promising topical treatment for CL. Not only the ease of obtaining or synthesizing the organic compounds evaluated in this work but also their commercial availability eliminates one of the most important barriers or bottlenecks in drug development, thus facilitating the roadmap for the development of a topical drug for the management of CL caused by L. braziliensis.


Assuntos
Alcaloides , Antiprotozoários , Benzodioxóis , Curcumina , Leishmania braziliensis , Leishmaniose Cutânea , Piperidinas , Alcamidas Poli-Insaturadas , Cricetinae , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Curcumina/farmacologia , Leishmaniose Cutânea/parasitologia , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Mesocricetus , Antiprotozoários/farmacologia
19.
Biomedicines ; 12(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38540100

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignancy prevailing in Taiwan, Hong Kong, Southern China, Southeast Asia, and North Africa. Although early-stage NPC responds well to the primary treatment of radio-chemotherapy, the mortality rate of advanced NPC remains high. Therefore, developing new therapies for nasopharyngeal carcinoma is an urgent task. Emodin is an anthraquinone derivative mainly found in Rheum palmatum. Emodin has been found to possess many anti-cancer functions against various types of cancers, but they are less discussed in the treatment of NPC. This review organized the different studies about the anti-NPC activity of emodin and discussed the potential and challenges of emodin treatment in NPC therapy.

20.
Toxicol Rep ; 12: 307-317, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38495473

RESUMO

The loofah/sponge gourd Luffa cylindrica (L.), a member of the Cucurbitaceae family, is one of the neglected medicinal plants. Traditionally, Luffa cylindrica is prescribed for inducing labor. It has a long history of use in China for the treatment of fever, diabetes, dyspnea, and dysentery. This study investigated the toxicity profile of the alkaloid-rich fraction of Luffa cylindrica (ARF-LC) for the first time in Sprague Dawley rats. A total of 80 rats (40 male and 40 female rats) aged 13 weeks old and weighing 200-220 g were selected for this study. In SD rats, sub-chronic oral toxicity was investigated at doses of 100, 200, and 400 mg/kg/d for a total of 90 days, followed by a 30-day recovery period. The results showed no variation in body weight among the three dose groups compared to the control group. Treatment-related adverse events, such as alterations in hematology and serum biochemistry parameters and the histology of the liver were sporadic in the high-dose rats but within the reference range. However, these changes disappeared after the doses were withdrawn during the recovery period. In conclusion, the "no observed adverse effect level" (NOAEL) of oral administration of ARF-LC in SD rats was considered 400 mg/kg/d and can be studied for its potential in further in vivo chronic investigations.

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