RESUMO
Multidrug-resistant Pseudomonas aeruginosa is a common pathogen that causes topical infections following burn injuries. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach for treating antibiotic-resistant bacterial infections. The objective of this study was to evaluate the aPDT efficacy of aloe-emodin (AE), which is a photosensitizer extracted from traditional Chinese herbs, on antibiotic-sensitive and antibiotic-resistant P. aeruginosa in vitro. In this study, we confirmed the effectiveness of AE-mediated aPDT against both standard and MDR P. aeruginosa, explored the effects of irradiation time and AE concentration on bacterial survival in AE-mediated aPDT, and observed the structural damage of P. aeruginosa by using transmission electron microscope. Our results showed that neither AE nor light irradiation alone caused cytotoxic effects on P. aeruginosa. However, AE-mediated aPDT effectively inactivated both antibiotic-sensitive and antibiotic-resistant P. aeruginosa. The transmission electron microscope investigation showed that aPDT mediated by AE primarily caused damage to the cytoplasm and cell membrane. Our findings suggest that AE is a photosensitizer in the aPDT of MDR P. aeruginosa-caused topical infections following burn injuries. Future investigations will concentrate on the safety and efficacy of AE-mediated aPDT in animal models and clinical trials.
Assuntos
Aloe , Anti-Infecciosos , Queimaduras , Emodina , Fotoquimioterapia , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Emodina/farmacologia , Fotoquimioterapia/métodos , Anti-Infecciosos/farmacologia , Queimaduras/tratamento farmacológicoRESUMO
Glioblastoma (GBM) is a highly aggressive cancer that currently lacks effective treatments. Pyroptosis has emerged as a promising therapeutic approach for cancer, but there is still a need for new pyroptosis boosters to target cancer cells. In this study, it is reported that Aloe-emodin (AE), a natural compound derived from plants, can inhibit GBM cells by inducing pyroptosis, making it a potential booster for pyroptosis-mediated GBM therapy. However, administering AE is challenging due to the blood-brain barrier (BBB) and its non-selectivity. To overcome this obstacle, AE@ZIF-8 NPs are developed, a biomineralized nanocarrier that releases AE in response to the tumor's acidic microenvironment (TAM). Further modification of the nanocarrier with transferrin (Tf) and polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) improves its penetration through the BBB and tumor targeting, respectively. The results show that AE-NPs (Tf-PEG-PLGA modified AE@ZIF-8 NPs) significantly increase the intracranial distribution and tumor tissue accumulation, enhancing GBM pyroptosis. Additionally, AE-NPs activate antitumor immunity and reduce AE-related toxicity. Overall, this study provides a new approach for GBM therapy and offers a nanocarrier that is capable of penetrating the BBB, targeting tumors, and attenuating toxicity.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Glioblastoma/patologia , Piroptose , Linhagem Celular Tumoral , Transferrina , Neoplasias Encefálicas/tratamento farmacológico , Microambiente TumoralRESUMO
African swine fever (ASF) is an acute infectious haemorrhagic fever of pigs caused by African swine fever virus (ASFV). Aloe-emodin (Ae) is an active ingredient of Chinese herbs with antiviral, anticancer, and anti-inflammatory effects. We investigated the antiviral activity and mechanism of action of Ae against ASFV using Real-time quantitative PCR (qPCR), western blotting, and indirect immunofluorescence assays. Ae significantly inhibited ASFV replication. Furthermore, transcriptomic analysis revealed that ASFV infection activated the NF-κB signaling pathway in the early stage and the apoptosis pathway in the late stage. Ae significantly downregulated the expression levels of MyD88, phosphor-NF-κB p65, and pIκB proteins as well as the mRNA levels of IL-1ß and IL-8 in porcine alveolar macrophages (PAMs) infected with ASFV, thereby inhibiting the activation of the NF-κB signaling pathway induced by ASFV. Flow cytometry and western blot analysis revealed that Ae significantly increased the percentage of ASFV-induced apoptotic cells. Additionally, Ae promoted apoptosis by upregulating the expression levels of cleaved-caspase3 and Bax proteins and downregulating the expression levels of Bcl-2 proteins. This suggests that Ae promotes apoptosis by inhibiting the NF-κB pathway, resulting in inhibition of ASFV replication. These findings have further improved therapeutic reserves for the prevention and treatment of ASF.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Aloe , Emodina , Animais , Vírus da Febre Suína Africana/genética , Aloe/metabolismo , Antivirais/farmacologia , Apoptose , Emodina/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais , Suínos , Replicação ViralRESUMO
Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.
Assuntos
Íleus , Plantas Medicinais , Humanos , Canal de Cátion TRPA1 , Íleus/tratamento farmacológico , Dor , Extratos Vegetais , Canais de Cátion TRPV/fisiologiaRESUMO
Aloe-emodin (AE) has been shown to inhibit the proliferation of several cancer cell lines, including human nasopharyngeal carcinoma (NPC) cell lines. In this study, we confirmed that AE inhibited malignant biological behaviors, including cell viability, abnormal proliferation, apoptosis, and migration of NPC cells. Western blotting analysis revealed that AE upregulated the expression of DUSP1, an endogenous inhibitor of multiple cancer-associated signaling pathways, resulting in blockage of the extracellular signal-regulated kinase (ERK)-1/2, protein kinase B (AKT), and p38-mitogen activated protein kinaseï¼p38-MAPKï¼ signaling pathways in NPC cell lines. Moreover, the selective inhibitor of DUSP1, BCI-hydrochloride, partially reversed the AE-induced cytotoxicity and blocked the aforementioned signaling pathways in NPC cells. In addition, the binding between AE and DUSP1 was predicted via molecular docking analysis using AutoDock-Vina software and further verified via a microscale thermophoresis assay. The binding amino acid residues were adjacent to the predicted ubiquitination site (Lys192) of DUSP1. Immunoprecipitation with the ubiquitin antibody, ubiquitinated DUSP1 was shown to be upregulated by AE. Our findings revealed that AE can stabilize DUSP1 by blocking its ubiquitin-proteasome-mediated degradation and proposed an underlying mechanism by which AE-upregulated DUSP1 may potentially target multiple pathways in NPC cells.
Assuntos
Aloe , Emodina , Neoplasias Nasofaríngeas , Humanos , Emodina/farmacologia , Carcinoma Nasofaríngeo , Ubiquitina , Simulação de Acoplamento Molecular , Transdução de Sinais , Apoptose , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Fosfatase 1 de Especificidade Dupla/metabolismoRESUMO
Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.
Assuntos
Aloe , Emodina , Sepse , Camundongos , Animais , Emodina/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Punções/efeitos adversos , Ligadura/efeitos adversos , Sepse/tratamento farmacológico , Sepse/etiologia , Ceco/cirurgia , Modelos Animais de DoençasRESUMO
Post-stroke depression (PSD) is a common complication of stroke that can damage patients' brains. More and more studies have been conducted on PSD in recent years, but the exact mechanism is still not understood. Currently, animal models provide an alternative approach to better understand the pathophysiology of PSD and may also pave the way for the discovery of new treatments for depression. This study investigated the therapeutic effect and mechanism of aloe-emodin (AE) on PSD rats. Previous studies have shown that AE positively affects PSD in rats by improving depression, increasing their activities and curiosities, enhancing the number of neurons, and ameliorating damage to brain tissue. Meanwhile, AE could up-regulate the expression of brain-derived neurotrophic factor (BDNF) and neurotrophic 3 (NTF3), but it could also down-regulate the expression of aquaporins (AQP3, AQP4, and AQP5), glial fibrillary acidic protein (GFAP), and transient receptor potential vanilloid 4 (TRPV4), which is helpful in maintaining homeostasis and alleviating encephaledema. AE may be a prospective solution in the future for the treatment of PSD patients.
Assuntos
Aloe , Emodina , Acidente Vascular Cerebral , Ratos , Animais , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Emodina/uso terapêutico , Ratos Sprague-Dawley , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Canais de Cátion TRPV/metabolismoRESUMO
Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described.
Assuntos
Neoplasias da Mama , Emodina , Polygonaceae , Rheum , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Extratos VegetaisRESUMO
To improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. However, the effects of FX-targeted IRF3 on the bacterial flora (which is disrupted in sepsis) and the mechanisms by which it impacts sepsis development remain unclear. This study aims to elucidate how FX-targeted IRF3 modulates intestinal microbiota compositions, influencing sepsis development. FX significantly reduced the bacterial load in the abdominal cavity of mice with cecal ligation and puncture (CLP)-induced sepsis via IRF3 activation and increased short-chain fatty acids, like acetic and propionic acids, with respect to their intestines. FX also altered the structure of the intestinal flora, notably elevating beneficial Verrucomicrobiota and Akkermansia spp. while reducing harmful Morganella spp. Investigating the inflammation-flora link, we found positive correlations between the abundances of Morganella spp., Proteus spp., Escherichia spp., and Klebsiella spp. and pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) induced by CLP. These bacteria were negatively correlated with acetic and propionic acid production. FX alters microbial diversity and promotes short-chain fatty acid production in mice with CLP-induced sepsis, reshaping gut homeostasis. These findings support the value of FX for the treatment of sepsis.
Assuntos
Microbioma Gastrointestinal , Microbiota , Sepse , Humanos , Animais , Camundongos , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Sepse/tratamento farmacológico , Citocinas , Fator Regulador 3 de InterferonRESUMO
The leaves of Asphodelus bento-rainhae subsp. bento-rainhae, an endemic Portuguese species, and Asphodelus macrocarpus subsp. macrocarpus have been used as food, and traditionally as medicine, for treating ulcers, urinary tract, and inflammatory disorders. The present study aims to establish the phytochemical profile of the main secondary metabolites, together with the antimicrobial, antioxidant and toxicity assessments of both Asphodelus leaf 70% ethanol extracts. Phytochemical screenings were conducted by the TLC and LC-UV/DAD-ESI/MS chromatographic technique, and quantification of the leading chemical classes was performed by spectrophotometric methods. Liquid-liquid partitions of crude extracts were obtained using ethyl ether, ethyl acetate, and water. For in vitro evaluations of antimicrobial activity, the broth microdilution method, and for the antioxidant activity, the FRAP and DPPH methods were used. Genotoxicity and cytotoxicity were assessed by Ames and MTT tests, respectively. Twelve known compounds including neochlorogenic acid, chlorogenic acid, caffeic acid, isoorientin, p-coumaric acid, isovitexin, ferulic acid, luteolin, aloe-emodin, diosmetin, chrysophanol, and ß-sitosterol were identified as the main marker compounds, and terpenoids and condensed tannins were found to be the major class of secondary metabolites of both medicinal plants. The ethyl ether fractions demonstrated the highest antibacterial activity against all the Gram-positive microorganisms, (MIC value of 62 to 1000 µg/mL), with aloe-emodin as one of the main marker compounds highly active against Staphylococcus epidermidis (MIC value of 0.8 to 1.6 µg/mL). Ethyl acetate fractions exhibited the highest antioxidant activity (IC50 of 800 to 1200 µg/mL, respectively). No cytotoxicity (up to 1000 µg/mL) or genotoxicity/mutagenicity (up to 5 mg/plate, with/without metabolic activation) were detected. The obtained results contribute to the knowledge of the value and safety of the studied species as herbal medicines.
Assuntos
Anti-Infecciosos , Emodina , Plantas Medicinais , Extratos Vegetais/química , Antioxidantes , Portugal , Plantas Medicinais/química , Anti-Infecciosos/química , Compostos Fitoquímicos/química , Etanol , Etil-Éteres , Testes de Sensibilidade MicrobianaRESUMO
Glioblastoma, the most dangerous and aggressive type of CNS tumor, appears resistant to many chemotherapy drugs. In the patient-derived glioma cell lines NULU and ZAR, which exhibit drug-resistant phenotypes, we investigated the effect of combined AE (Aloe-emodin) and TMZ (temozolomide) and found a significant additive inhibitory effect on cell growth and a promising cytotoxic effect on both cell lines compared to treatment with single agents. We also examined the effect of combined AE and TMZ treatment on the drug-resistance protein MGMT. The results suggest that using AE combined with traditional drugs restores drug resistance in both primary resistant cell lines (NULU and ZAR). Furthermore, migration assays and scratch tests showed that the combined use of AE and TMZ can slow down the colony formation and migration of glioblastoma cells. These convincing results suggest that AE could be a natural adjuvant agent to potentiate the effects of traditional drugs (TMZ) and overcome drug resistance in glioblastoma cells.
Assuntos
Aloe , Emodina , Glioblastoma , Humanos , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Linhagem CelularRESUMO
Cationic water-based polyurethane(CWPU) was synthesized to explore aloe-emodin modifies to obtain CWPU materials with better comprehensive performance. It provides a simple way to synthesize antibacterial waterborne polyurethane, which is to introduce the end-blocking group of herbal extracts into the structure. It contains synergistic antibacterial effect of herbal antibacterial and quaternary ammonium ion on Escherichia coli. It makes the material resist the erosion of bacterial, and increase the service life of materials. When the pH value of the environment changes, the UV absorbance of the aloe-emodin modified cationic water-based polyurethane(AE-CWPU) also changes. Therefore, within a certain detection range, AE-CWPU has great applications in the field of smart response materials. The modified thermodynamic properties have been improved, and the mechanical properties basically maintained the maximum stress, and the elongation at break was reduced.
RESUMO
The dramatic rise in drug resistance accelerated the desire for new antibacterial agents to safeguard human health. This work constructed a novel type of aloe emodin-hybridized sulfonamide aminophosphates as unique potential antibacterial agents. The biological assay revealed that some target hybrids possessed potent inhibitory activity. Particularly, ethyl aminophosphate-hybridized sulfadiazine aloe emodin 7a (EASA-7a) not only displayed preponderant antibacterial efficiency against drug-resistant E. faecalis at low concentration as 0.25 µg/mL but also possessed strong bacteriostatic capacity and low propensity to develop resistance toward E. faecalis. The weak hemolysis toward human red blood cells and efficient biofilm-disruptive ability further implied the therapeutic potential of EASA-7a. Preliminary studies disclosed that the excellent antibacterial behavior of EASA-7a might be attributed to its capacity to permeate and depolarize the bacterial membrane, as well as promote ROS accumulation and intercalate with DNA. These findings manifested that EASA-7a was worthy of further development to combat life-threatening bacterial infections.
Assuntos
Enterococcus faecalis , Substâncias Intercalantes , Antraquinonas/farmacologia , Antibacterianos/farmacologia , Humanos , SulfanilamidaRESUMO
Aloe emodin-conjugated sulfonyl hydrazones were designed and synthesized as novel type of antibacterial modulators. Aloe emodin benzenesulfonyl hydrazone 5a (AEBH-5a) was preponderant for the treatment of S. aureus 25923 (MIC = 0.5 µg/mL) over norfloxacin and presented high selectivity between bacterial membranes and mammalian membranes. Especially, AEBH-5a could eliminate the formed biofilms and relieve the development of S. aureus 25923 resistance. The antibacterial mechanism of AEBH-5a from extracellularity to intracellularity illustrated that AEBH-5a could destroy bacterial membrane integrity, leading to the leakage of protein and nucleic acid. Besides, AEBH-5a could not only interact with DNA and induce oxidative stress but also inhibit lactate dehydrogenase (LDH) activity as well as render metabolic inactivation. In silico ADME studies prediction of AEBH-5a revealed a favorable bioavailability score and prominent drug-likeness profile. This research showed that the multifaceted synergistic effect initiated by aloe emodin-conjugated sulfonyl hydrazones is a reasonable and effective tactic to combat menacing bacterial infections.
Assuntos
Emodina , Staphylococcus aureus Resistente à Meticilina , Animais , Antraquinonas , Antibacterianos/farmacologia , Bactérias , Emodina/farmacologia , Hidrazonas/farmacologia , Mamíferos , Staphylococcus aureusRESUMO
Skin cancer (melanoma and non-melanoma) is the most frequent type of malignancy in the Caucasian population. Photodynamic therapy (PDT) as an interesting and unique strategy may potentially boost standard therapeutic approaches. In the present study, the potential of emodin and aloe-emodin as photosensitizers in photodynamic therapy has been investigated. The conducted research presents for the first-time comparison of the phototoxic and anti-cancerous effects of emodin and aloe-emodin on skin cancer cell lines, including SCC-25 representing cutaneous squamous cell carcinoma, MUG-Mel2 representing a melanoma cell line, and normal human keratinocytes HaCaT representing control normal skin cells. To assess the effectiveness of emodin and aloe-emodin as a photosensitizer in PDT on different skin cell lines, we performed MTT assay measuring cytotoxicity of natural compounds, cellular uptake, apoptosis with flow cytometry, and a wound-healing assay. Although emodin and aloe-emodin are isomers and differ only in the position of one hydroxyl group, our phototoxicity and apoptosis detection results show that both substances affect skin cancer cells (SSC-25 squamous cell carcinoma and MUG-Mel2 melanoma) and normal keratinocytes (HaCaT cell line) in other ways. In conclusion, our study provides evidence suggesting that emodin and aloe-emodin mediated PDT exhibits the potential for clinical development as a new effective and safe photosensitizer to treat skin cancer.
Assuntos
Aloe , Carcinoma de Células Escamosas , Emodina , Melanoma , Fotoquimioterapia , Neoplasias Cutâneas , Antraquinonas/farmacologia , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Emodina/farmacologia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Metastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.
Assuntos
Emodina , Segunda Neoplasia Primária , Humanos , Emodina/farmacologia , Antraquinonas/farmacologia , Metabolômica , Melanoma Maligno CutâneoRESUMO
A series of novel aloe-emodin-coumarin hybrids were designed and synthesized. The antitumor activity of these derivatives was evaluated against five human tumor cell lines (A549, SGC-7901, HepG2, MCF-7 and HCT-8). Some of the synthesized compounds exhibited moderate to good activity against one or more cell lines. Particularly, compound 5d exhibited more potent antiproliferative activity than the reference drug etoposide against all tested tumor cell lines, indicating that it had a broad spectrum of antitumor activity and that it may provide a promising lead compound for further development as an antitumor agent by structural modification. Furthermore, the structure-activity relationship study of the synthesized compounds was also performed.
Assuntos
Aloe , Antineoplásicos , Emodina , Antraquinonas , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Cumarínicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Emodina/farmacologia , Etoposídeo/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Breast cancer is one of the most diffuse cancers in the world and despite the availability of the different drugs employed against it, the need for new and particularly more specific molecules is ever growing. In this framework, natural products are increasingly assuming an important role as new anticancer drugs. Aloe-emodin (AE) is one of the best characterized molecules in this field. The functionalization of bioactive natural products with selected peptide sequences to enhance their bioavailability and specificity of action is a powerful and promising strategy. In this study, we analyzed the cell specificity, cell viability effects, intracellular distribution, and immune cell response of a new peptide conjugate of Aloe-emodin in SKBR3 and A549 cell lines by means of viability tests, flow cytometry, and confocal microscopy. The conjugate proved to be more effective at reducing cell viability than AE in both cell lines. Furthermore, the results showed that it was mainly internalized within the SKBR3 cells, showing a nuclear localization, while A459 cells displayed mainly a cytoplasmic distribution. A preserving effect of the conjugate on NKs' cell function was also observed. The designed conjugate showed a promising specific activity towards HER2-expressing cells coupled with an enhanced water solubility and a higher cytotoxicity; thus, the resulting proof-of-concept molecule can be further improved as an anticancer compound.
Assuntos
Aloe , Antineoplásicos , Produtos Biológicos , Neoplasias da Mama , Emodina , Aloe/química , Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Apoptose , Produtos Biológicos/farmacologia , Emodina/farmacologia , Feminino , Humanos , Peptídeos/farmacologiaRESUMO
In this study, ultrasound-assisted extraction conditions were optimized to maximize the yields of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol from S. alexandrina (aerial parts). The three UAE factors, extraction temperature (S1), extraction time (S2), and liquid to solid ratio (S3), were optimized using response surface methodology (RSM). A Box-Behnken design was used for experimental design and phytoconstituent analysis was performed using high-performance liquid chromatography-UV. The optimal extraction conditions were found to be a 64.2 °C extraction temperature, 52.1 min extraction time, and 25.2 mL/g liquid to solid ratio. The experimental values of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol (2.237, 12.792, 2.457, 0.261, and 1.529%, respectively) agreed with those predicted (2.152, 12.031, 2.331, 0.214, and 1.411%, respectively) by RSM models, thus demonstrating the appropriateness of the model used and the accomplishment of RSM in optimizing the extraction conditions. Excellent antioxidant properties were exhibited by S. alexandrina methanol extract obtained using the optimized extraction conditions with a DPPH assay (IC50 = 59.7 ± 1.93, µg/mL) and ABTS method (47.2 ± 1.40, µg/mL) compared to standard ascorbic acid.
Assuntos
Antioxidantes/farmacologia , Fracionamento Químico/métodos , Componentes Aéreos da Planta/química , Extrato de Senna/farmacologia , Senna/química , Sonicação , Ondas Ultrassônicas , Algoritmos , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga , Modelos Teóricos , Estrutura Molecular , Compostos Fitoquímicos , Extrato de Senna/química , Extrato de Senna/isolamento & purificaçãoRESUMO
The anti-inflammatory effects of Aloe vera (AV), polysaccharide extract from AV, and extracts from the digestion and colonic fermentation of AV were evaluated using an immortal astrocyte cell line (U373 MG) that develops a neuro-inflammatory profile. Cell viability and inflammatory markers were assessed after stimulation with neuropeptide substance P (SP) that activates the pro-inflammatory MAPK (mitogen-activated protein kinase) pathway. Cell viability after SP treatment was over 50% at 10 mg/mL AV, polysaccharide extract from AV, extracts from the digestion: non-digestible fraction of AV non-digestible fraction of polysaccharide extract from AV and extracts from the colonic fermentation of AV, at 4 and 24 h. Moreover, cells exposed to SP and treated with these extracts showed lower protein-activated ERK1/ERK2 (extracellular signal-regulated kinases 1 and 2), p38 (MAPK protein p38), and NFκB (nuclear factor κB) levels with respect to the SP-stimulated control. Inflammation inhibition by extracts of polysaccharide extract from AV and extracts from the colonic fermentation of AV, at 24 h in the study of p38 was not as statistically significant in ERK1/ERK2 and NFκB. Nevertheless, there was a significant decrease (p < 0.05) in pro-inflammatory cytokine IL-6 levels in cells exposed to all samples. Samples with extracts from the colonic fermentation of AV, at 4 or 24 h showed the highest inhibitory effect on IL-6 production.