RESUMEN
In this work, the electrochemical behavior of the glycosylated flavonoid kaempferitrin was studied, and an electroanalytical methodology was developed for its determination in infusions of Bauhinia forficata using a boron-doped diamond electrode (BDD). The electrochemical behavior of the flavonoid was studied by cyclic voltammetry, and two irreversible oxidation peaks at 0.80 and 1.0 V vs Ag/AgCl were observed. The influence of the pH on the voltammograms was examined, and higher sensitivity was found at pH 7.0. The electrochemical process corresponding to peak 1 at 0.80 V is predominantly diffusion-controlled, as the study shows at varying scan rates. An analytical plot was obtained by square wave voltammetry at optimized experimental conditions (frequency = 100 s-1, amplitude = 90 mV, and step potential = 8 mV) in the concentration range from 3.4 µmol L-1 to 58 µmol L-1, with a linearity of 0.99. The limit of detection and limit of quantification values were 1.0 µmol L-1 and 3.4 µmol L-1, respectively. Three samples of Bauhinia forficata infusions (2 g of sample in 100 mL of water) were analyzed, and the KF values found were 5.0 × 10-4 mol L-1, 3.0 × 10-4 mol L-1, and 7.0 × 10-4 mol L-1, with recovery percentages of 98 %, 106 % and 94 %, respectively. Finally, experiments were performed with two other flavonoids (chrysin and apeginin) to compare and propose an electrochemical oxidation mechanism for kaempferitrin, which was supported by quantum chemical calculations.
Asunto(s)
Técnicas Electroquímicas , Quempferoles , Oxidación-Reducción , Quempferoles/química , Quempferoles/análisis , Técnicas Electroquímicas/métodos , Glicosilación , Electrodos , Bauhinia/química , Teoría Cuántica , Flavonoides/química , Flavonoides/análisis , Límite de Detección , Diamante/químicaRESUMEN
AIM: Kaempferitrin is an active component in Chenopodium ambrosioides, showing medicinal functions against liver cancer. This study aimed to identify the potential targets and pathways of kaempferitrin against liver cancer using network pharmacology and molecular docking, and verify the essential hub targets and pathway in mice model of SMMC-7721 cells xenografted tumors and SMMC-7721 cells. METHODS: Kaempferitrin therapeutical targets were obtained by searching SwissTargetPrediction, PharmMapper, STITCH, DrugBank, and TTD databases. Liver cancer specific genes were obtained by searching GeneCards, DrugBank, TTD, OMIM, and DisGeNET databases. PPI network of "kaempferitrin-targets-liver cancer" was constructed to screen the hub targets. GO, KEGG pathway and MCODE clustering analyses were performed to identify possible enrichment of genes with specific biological subjects. Molecular docking and molecular dynamics simulation were employed to determine the docking pose, potential and stability of kaempferitrin with hub targets. The potential anti-liver cancer mechanisms of kaempferitrin, as predicted by network pharmacology analyses, were verified by in vitro and in vivo experiments. RESULTS: 228 kaempferitrin targets and 2186 liver cancer specific targets were identified, of which 50 targets were overlapped. 8 hub targets were identified through network topology analysis, and only SIRT1 and TP53 had a potent binding activity with kaempferitrin as indicated by molecular docking and molecular dynamics simulation. MCODE clustering analysis revealed the most significant functional module of PPI network including SIRT1 and TP53 was mainly related to cell apoptosis. GO and KEGG enrichment analyses suggested that kaempferitrin exerted therapeutic effects on liver cancer possibly by promoting apoptosis via p21/Bcl-2/Caspase 3 signaling pathway, which were confirmed by in vivo and in vitro experiments, such as HE staining of tumor tissues, CCK-8, qRT-PCR and Western blot. CONCLUSION: This study provided not only insight into how kaempferitrin could act against liver cancer by identifying hub targets and their associated signaling pathways, but also experimental evidence for the clinical use of kaempferitrin in liver cancer treatment.
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Quempferoles , Neoplasias Hepáticas , Simulación del Acoplamiento Molecular , Animales , Humanos , Quempferoles/farmacología , Quempferoles/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Ratones , Línea Celular Tumoral , Farmacología en Red , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Ratones DesnudosRESUMEN
Exosomes, small yet vital extracellular vesicles, play an integral role in intercellular communication. They transport critical components, such as proteins, lipid bilayers, DNA, RNA, and glycans, to target cells. These vesicles are crucial in modulating the extracellular matrix and orchestrating signal transduction processes. In oncology, exosomes are pivotal in tumor growth, metastasis, drug resistance, and immune modulation within the tumor microenvironment. Exosomal proteins, noted for their stability and specificity, have garnered widespread attention. This review delves into the mechanisms of exosomal protein loading and their impact on tumor development, with a focus on the regulatory effects of natural products and traditional Chinese medicine on exosomal protein loading and function. These insights not only offer new strategies and methodologies for cancer treatment but also provide scientific bases and directions for future clinical applications.
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Productos Biológicos , Exosomas , Medicina Tradicional China , Neoplasias , Humanos , Exosomas/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Tubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti-inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model-induced renal inflammation and fibrosis. In vitro, erastin-induced ferroptosis in primary tubular epithelial cells (TECs) was utilized to further explore Kaempferitrin's effects. Additionally, NADPH oxidase 4 (NOX4) transfection in TECs and cellular thermal shift assay (CETSA) were conducted to identify Kaempferitrin's target protein. Kaempferitrin effectively improved renal function, indicated by reduced serum creatinine and blood urea nitrogen levels. In the UUO model, it significantly reduced tubular necrosis, inflammation, and fibrosis. Its renoprotective effects were linked to ferroptosis inhibition, evidenced by decreased iron, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) levels, and increased glutathione (GSH). Kaempferitrin also normalized glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11(SLC7A11) expression, critical ferroptosis mediators. In vitro, it protected TECs from ferroptosis and consistently suppressed NOX4 expression. NOX4 transfection negated Kaempferitrin's antiferroptosis effects, while CETSA confirmed Kaempferitrin-NOX4 interaction. Kaempferitrin shows promise as a nephroprotective agent by inhibiting NOX4-mediated ferroptosis in tubular cells, offering potential therapeutic value for CKD.
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Ferroptosis , Fibrosis , NADPH Oxidasa 4 , Obstrucción Ureteral , Animales , Ferroptosis/efectos de los fármacos , NADPH Oxidasa 4/metabolismo , Ratones , Fibrosis/tratamiento farmacológico , Obstrucción Ureteral/tratamiento farmacológico , Masculino , Quempferoles/farmacología , Ratones Endogámicos C57BL , Inflamación/tratamiento farmacológico , Modelos Animales de Enfermedad , Bauhinia/química , Túbulos Renales/patología , Túbulos Renales/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Células Epiteliales/efectos de los fármacosRESUMEN
BACKGROUND: Acute lung injury (ALI) causes severe and uncontrolled pulmonary inflammation and has high morbidity in dying patients. OBJECTIVE: This study aimed to evaluate the potential function of Kaempferitrin (Kae) and uncover its mechanisms in ALI. MATERIAL AND METHODS: We evaluated the role of Kae in ALI through the lipopolysaccharide (LPS)-induced histopathological changes, lung wet/dry (W/D) ratio, total bronchoalveolar lavage fluid (BALF) cells count, pulmonary inflammation, and the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1ß. The effect of Kae on NF-κB signaling pathway was discovered through the protein expression levels of transcription factors p65, p-p65, IκBα, and p-IκBα by Western blot analysis. RESULTS: The results showed that Kae could improve lung injury by reducing apoptosis, histopathological changes, and lung W/D ratio; more importantly, Kae enhanced the survival of ALI mice. Moreover, Kae relieved inflammation, as it reduced total BALF cells count, and deceased the levels of TNF-α, IL-6, and IL-1ß in serum. In addition, Western blot analysis data suggested that Kae could decrease the protein expression levels of transcription factors p65, p-p65, IκB-α, and p-IκB-α, which were promoted by LPS. CONCLUSION: The results of this study suggested that Kae could relieve LPS-induced ALI in mice and reduce inflammation and apoptosis through NF-κB pathway.
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Lesión Pulmonar Aguda , Neumonía , Humanos , Ratones , Animales , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa , Lipopolisacáridos/efectos adversos , Factor de Necrosis Tumoral alfa/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Pulmón/patología , Interleucina-6 , Inflamación/patología , Neumonía/patologíaRESUMEN
OBJECTIVESï¼: This study aimed to investigate antitumour effect and possible toxicity of kaempferitrin, the major compound from ethanol extract of Chenopodium ambrosioides, in the mice model of human liver cancer xenografts. METHODSï¼: Forty mice bearing SMMC-7721 cells xenografts were divided into control group (not treated) and three groups orally administered with ethanol extract of C. ambrosioides, kaempferol (positive control) and kaempferitrin for 30 days. Antitumour effect was evaluated by measurement of tumour growth, histological examinations of tumours, flow cytometry detection of splenic CD19+ B lymphocytes and CD161+ Natural Killer cells, biochemical measurements of serum levels of tumour necrosis factor-α, interleukin-6, interferon-γ, malonaldehyde, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenz thiazoline-6-sulphonate) radicals. Toxicity was evaluated by histological examinations of livers and measurements of serum levels of aspartate transaminase, alanine transaminase, total bilirubin, direct bilirubin, malonaldehyde and hepatic malonaldehyde level. KEY FINDINGS: Kaempferitrin significantly (P < 0.05) decreased tumour volume, mass and cell number. Antitumour effect was due to induction of tumour cells necrosis and apoptosis, stimulation of splenic B lymphocytes, decreases of radicals and malonaldehyde. Kaempferitrin did not change liver structure, and decreased serum levels of transaminases, bilirubin, malonaldehyde and hepatic malonaldehyde level. CONCLUSIONS: Kaempferitrin exerts antitumour and hepatoprotective effects.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Chenopodium ambrosioides , Neoplasias Hepáticas , Humanos , Ratones , Animales , Quempferoles/farmacología , Chenopodium ambrosioides/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Etanol , Xenoinjertos , Hígado , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Modelos Animales de Enfermedad , Bilirrubina/farmacología , Malondialdehído , Enfermedad Hepática Inducida por Sustancias y Drogas/patologíaRESUMEN
C. oleifera is an economically important oilseed crop and medical plant. However, as a characteristic honey resource, the standard protocol used to identify the composition of C. oleifera honey has not been established yet. Previously, distinctive flavonoid has been shown as an effective marker to trace the botanical origin of honey. In this study, we examined the flavonoid types in C. oleifera honey and nine other monofloral honeys by using liquid chromatography tandem-mass spectrometry (LC-MS/MS) and compared the differences and identified eight distinct flavonoids in C. oleifera honey. Then, comparing the 8 flavonoids with the 14 flavonoids common to C. oleifera honey and nectar, two distinct flavonoids were identified in C. oleifera honey and nectar. Finally, we identified kaempferitrin as the distinct flavonoid marker in C. oleifera honey using the degree of influence of the partial least-squares discriminant analysis (PLS-DA) model on C. oleifera honey and ployfloral honey.
Asunto(s)
Miel , Miel/análisis , Flavonoides/química , Néctar de las Plantas , Cromatografía Liquida , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en TándemRESUMEN
Background: Acute lung injury (ALI) causes severe and uncontrolled pulmonary inflammation and has high morbidity in dying patients. Objective: This study aimed to evaluate the potential function of Kaempferitrin (Kae) and uncover its mechanisms in ALI. Material and Methods: We evaluated the role of Kae in ALI through the lipopolysaccharide (LPS)-induced histopathological changes, lung wet/dry (W/D) ratio, total bronchoalveolar lavage fluid (BALF) cells count, pulmonary inflammation, and the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β. The effect of Kae on NF-κB signaling pathway was discovered through the protein expression levels of transcription factors p65, p-p65, IκBα, and p-IκBα by Western blot analysis. Results: The results showed that Kae could improve lung injury by reducing apoptosis, histopathological changes, and lung W/D ratio; more importantly, Kae enhanced the survival of ALI mice. Moreover, Kae relieved inflammation, as it reduced total BALF cells count, and deceased the levels of TNF-α, IL-6, and IL-1β in serum. In addition, Western blot analysis data suggested that Kae could decrease the protein expression levels of transcription factors p65, p-p65, IκB-α, and p-IκB-α, which were promoted by LPS. Conclusion: The results of this study suggested that Kae could relieve LPS-induced ALI in mice and reduce inflammation and apoptosis through NF-κB pathway (AU)
Asunto(s)
Animales , Masculino , Ratones , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , FN-kappa B/metabolismo , Neumonía/patología , Sepsis , Inflamación/patología , Lipopolisacáridos/efectos adversos , Factor de Necrosis Tumoral alfa/metabolismo , Ratones Endogámicos C57BLRESUMEN
Neurodegenerative disorders occur when nerve cells in the brain or peripheral nervous system partial or complete fail in their functions and sometimes even die due to some injuries or aging. Neurodegenerative disorders such as Alzheimer's Disease (AD) and Parkinson's Disease (PD), have been majorly resulted due to degeneration of neurons and neuroinflammation progressively. There are many similarities that correlates both AD and PD on a cellular and sub-cellular level. Therefore, a hope for therapeutic advancement for simultaneous upgradation in both the diseases are directly depending on the discovery of common mechanism at molecular and cellular level. Recent and past evidences from scientific literature supporting the efficacy of plants flavonoids in treatment and protection of both AD and PD. Further, dietary flavones, specially Heptamethoxyflavone, Kaempferitrin, Vitexin and Amentoflavone gains recently much more attention for producing many health beneficiary effects including neuroprotection. Despite of these evidence a detailed updated overview of neuroprotective effects against both AD and PD by Heptamethoxyflavone, Kaempferitrin, Vitexin and Amentoflavone are still missing. In this context several published studies were assessed by using various online electronic search engines/databases to meet the objective from 1981 to 2021 (Approx. 224). Therefore, present review was designed to deliver the detailed description on these flavones including therapeutic benefits in AD, PD and other CNS complications with critical analysis on underlying mechanisms.
Asunto(s)
Enfermedad de Alzheimer , Flavonas , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Flavonas/farmacología , Flavonas/uso terapéutico , Enfermedades Neurodegenerativas/tratamiento farmacológicoRESUMEN
Bioactive metabolites from Bauhinia forficata Link (Bf extract) hold therapeutic potential for type 2 diabetes mellitus (T2DM) but the mechanism remains poorly understood. This study aimed to test the extract from Bf leaves obtained by decoction on the prevention of T2DM in vivo. The Bf extract was tested on a streptozotocin-induced T2DM mouse model fed on a high-fat diet. The insulin resistance was attenuated in T2DM animals supplemented with Bf extract, which indicates glucose intolerance reduction and p-AKT/AKT ratio preservation in the gastrocnemius muscle. These observations suggested that Bf extract enhanced glucose uptake. Nevertheless, there was no preservation in ß-cell insulin secretion in Bf extract-treated T2DM mice. Interestingly, the Bf extract reduced body weight gain without affecting total energy intake. Hence, Bf extract has a hypoglycemic effect which could attenuate the development of insulin resistance.
Asunto(s)
Bauhinia , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt , Hipoglucemiantes , Glucosa , Músculo Esquelético/metabolismo , Insulina , Glucemia/metabolismoRESUMEN
Clitoria guianensis and Ouratea spectabilis, found in the Brazilian Cerrado, are used in folk medicine, despite the few chemical and biological studies reported in the literature. The present study aims to investigate the toxicity and effect of extracts from both species on the microcrustacean Artemia salina, and to determine the chemical composition of the hexane extract of O. spectabilis leaves and the EtOAc fraction of C. guianensis leaves. Kaempferitrin, a flavonoid isolated from of the EtOAc fraction of C. guianensis leaves, was identified by chemical analysis. Analysis of the hexane extract of O. spectabilis leaves using gas chromatography-mass spectrometry (GC-MS) suggested the presence of twenty-five known substances. The Hex, EtOAc, and EtOH crude extracts of C. guianensis leaves exhibited high and moderate toxicity against Artemia salina, with median lethal dose values (LD50) of 43.7, 25.4, and 233.4 mg.L−1, respectively. The acetone extract of O. spectabilis leaves showed moderate toxicity against Artemia salina with an LD50 value of 115.13 mg.L−1.
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Artemia , Hojas de la Planta , Clitoria/toxicidad , Clitoria/química , Ochnaceae/toxicidad , Ochnaceae/químicaRESUMEN
An infusion from the aerial parts of Justicia spicigera Schltdl., an herb commonly used to treat diabetes, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B). Two undescribed compounds, 2-N-(p-coumaroyl)-3H-phenoxazin-3-one, and 3â³-O-acetyl-kaempferitrin, along with kaempferitrin, kaempferol 7-O-α-L-rhamnopyranoside, perisbivalvine B and 2,5-dimethoxy-p-benzoquinone were isolated from the active extract. Their structures were elucidated by a combination of spectroscopic and spectrometric methods. The isolates were evaluated for their inhibitory activity against PTP1B; the most active compounds were 2-N-(p-coumaroyl)-3H-phenoxazin-3-one, and perisbivalvine B with IC50 values of 159.1 ± 0.02 µM and 106.6 ± 0.01 µM, respectively. However, perisbivalvine B was unstable. Kinetic analysis of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one and 2,5-dimethoxy-p-benzoquinone (obtained in good amounts) indicated that both compounds behaved as parabolic competitive inhibitors and bind to the enzyme forming complexes with 1:1 and 1:2 stoichiometry. Docking of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one and 2,5-dimethoxy-p-benzoquinone to PTP1B1-400 predicted a good affinity of these compounds for PTP1B catalytic site and demonstrated that the binding of a second ligand is sterically possible. The 1:2 complex was also supported by the second docking analysis, which predicted an important contribution of π-stacking interactions to the stability of these 1:2 complexes. Finally, an UHPLC-MS method was developed and validated to quantify the content of kaempferitrin in the infusion of the plant.
Asunto(s)
Acanthaceae , Género Justicia , Benzoquinonas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Quempferoles/farmacología , Cinética , Ligandos , Simulación del Acoplamiento Molecular , Extractos Vegetales/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1RESUMEN
Polymeric nanoparticles are widely studied in the treatment of colorectal cancer. Kaempferitrin-loaded nontoxic and biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) developed by the solvent emulsion evaporation method by improving its solubility and bioavailability. In order to improve the delivery of kaempferitrin (KM) to cancerous cells, folic acid (FA) combined kaempfertrin PLGA NPs were prepared. The goal of the study was whether PLGA NPs with surface KM and FA could help to prevent colorectal cancer. The synthesis of KM with FA in a nanomedicine could be crucial in the development of colon cancer chemotherapeutics. The physicochemical characteristics of synthesized KM-entrapped PLGA NPs were investigated by XRD, FTIR, zeta potential, and TEM. The KM + FA + PLGA NPs showed particle size with 132.9 ± 1.4 nm, zeta potential -15.0 ± 1.73 mV, encapsulation efficiency 67.92 ± 4.8, and drug-loading capacity 0.463 ± 0.173. In vitro cytotoxicity study on HT-29 cell lines using the MTT assay, the apoptotic study revealed that KM + FA + PLGA NPs have an enhanced cytotoxic effect compared to the KM + PLGA NPs drug solution. These findings suggested that KM + FA + PLGA NPs could be an effective chemotherapeutic drug delivery system in colon adenocarcinoma HT-29 cells.
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Adenocarcinoma , Neoplasias del Colon , Nanopartículas , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Poliglicólico/química , Portadores de Fármacos/química , Ácido Fólico/química , Ácido Láctico , Nanopartículas/química , Tamaño de la PartículaRESUMEN
As components of the human diet with potential health benefits, flavonols are the subject of numerous studies, confirming their antioxidant, free radical scavenging and anti-inflammatory activity. Taking into consideration the postulated pathogenesis of certain CNS dysfunctions characterized by neuronal degradation, flavonols may prevent the decay of neurons in multiple pathways. Leaves of Maesa membranacea yielded several flavonol glycosides including α-rhamnoisorobin (kaempferol 7-O-α-rhamnoside) and kaempferitrin (kaempferol 3,7-di-O-α-rhamnoside). The latter compound was a major constituent of the investigated plant material. Neuroprotective effects of kaempferitrin and α-rhamnoisorobin were tested in vitro using H2O2-, 6-OHDA- and doxorubicin-induced models of SH-SY5Y cell damage. Both undifferentiated and differentiated neuroblastoma cells were used in the experiments. α-Rhamnoisorobin at a concentration range of 1-10 µM demonstrated cytoprotective effects against H2O2-induced cell damage. The compound (at 1-10 µM) was also effective in attenuating 6-OHDA-induced neurotoxicity. In both H2O2- and 6-OHDA-induced cell damage, kaempferitrin, similar to isoquercitrin, demonstrated neuroprotective activity at the highest of the tested concentrations (50 µM). The tested flavonols were not effective in counteracting doxorubicin-induced cytotoxicity. Their caspase-3- and cathepsin D-inhibitory activities appeared to be structure dependent. Inhibition of the PI3-K/Akt pathway abolished the neuroprotective effect of the investigated flavonols.
Asunto(s)
Catepsina D/metabolismo , Quempferoles , Maesa/química , Fármacos Neuroprotectores , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Humanos , Quempferoles/química , Quempferoles/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacologíaRESUMEN
BACKGROUND: Herbal drugs and their derived phytochemicals are valuable for human beings as a source of a vital component of food material and drugs. Flavonoids are naturally occurring phytochemicals produced in plants through metabolisms, and they have anti-hyperlipidemia, anti-inflammatory, anti-oxidant and anti-apoptotic activity. Flavonoids have been identified in fruits, nuts, vegetables, seeds, stems, flowers, and tea. Kaempferol is a natural flavonoidal compound present in edible plants such as apples, broccoli, strawberries, beans, grapefruit, propolis, and medicinal plants such as Aloe vera, Ginkgo biloba, Rosmarinus officinalis, Crocus sativus L., Hypericum perforatum L. Kaempferol have anti-oxidant, anti-inflammatory, anti-apoptotic, proapoptotic, cardio-protective and anti-cancer activities. METHODS: Glycosides of kaempferol such as kaempferitrin, also called kaempferol 3,7-dirhamnoside are known to be more abundant than their flavonoid monomers in plants. Various literature databases have been searched to collect all the scientific information of kaempferitrin in the present investigation and analyzed in order to know the therapeutic benefit and biological potential of kaempferitrin. Moreover, all the information has been presented here in two broad sections, i.e., pharmacological and analytical. RESULTS: From the analysis of all the collected and presented information, it was found that kaempferitrin has potent insulin-mimetic potential and could be used for the treatment of diabetes and related complications. However, it has also shown anti-oxidant, anti-inflammatory, anti-convulsant, anti-osteoporotic, anti-depressant, anthelmintic, immunostimulatory, and natriuretic properties and inhibits cell proliferation and apoptosis. Kaempferitrin also improves the meat quality of broiler chickens. CONCLUSION: The presented information in this work will be valuable to justify the biological importance and therapeutic potential of kaempferitrin in the scientific field.
Asunto(s)
Pollos , Quempferoles , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Flavonoides , Humanos , Quempferoles/farmacología , Quempferoles/uso terapéutico , Extractos VegetalesRESUMEN
Kaempferitrin is extracted in significantly high quantities from the leaves of Cinnamomum osmophloeum, which belongs to a group of plant species that comes under the genus Cinnamomum, well-known for its established anti-diabetic property in Chinese medicine. Oral administration of kaempferitrin and Cinnamomum osmophloeum extract reduced blood sugar in alloxan-induced diabetic rats and improved the lipid profile in hamsters respectively. In this paper we studied the differential protein expression profile using mass spectrometry approach in the kaempferitrin-treated conditioned medium of liver cancer cell line HepG2. We discovered that 33 genes were up/down-regulated consistently between two biological samples. A slightly different version of the analysis software selected 28 genes, and the final 18 genes that appeared in both lists were selected. Interestingly, 5 proteins out of 18 were either exosomal markers or reported in high frequency of occurrence in exosome/secreted vesicles. We also examined the extracellular particles with atomic force microscopy (AFM), which showed that the conditioned medium of kaempferitrin treated had larger vesicles and fewer small vesicles. Expression of some lipid-regulating genes were also altered. Our data suggested that extracellular vesicle secretions may be regulated by kaempferitrin, and regulation of lipid profile by kampeferitrin involves multiple mechanisms.
Asunto(s)
Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , Quempferoles/farmacología , Biomarcadores/análisis , Cinnamomum , Medios de Cultivo Condicionados/química , Bases de Datos de Proteínas , Células Hep G2 , Humanos , Metabolismo de los Lípidos , Medicina Tradicional China , Microscopía de Fuerza Atómica , Tamaño de la Partícula , Extractos Vegetales/farmacología , Hojas de la Planta/química , Proteómica , Programas InformáticosRESUMEN
Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitory activities on PD-1/PD-L1 protein-protein interaction (PPI), biochemical assays including competitive ELISA and biolayer interferometry (BLI) systems were performed. Cellular PD-1/PD-L1 blocking activity was measured in a co-culture system with PD-1 Jurkat and PD-L1/aAPC CHO-K1 cells by T-cell receptor (TCR) activation-induced nuclear factor of activated T cells (NFAT)-luciferase reporter assay. The detailed binding mode of action was simulated by an in silico docking study and pharmacophore analysis. Competitive ELISA revealed that KO and its glycoside KR significantly inhibited PD-1/PD-L1 interaction. Cellular PD-1/PD-L1 blocking activity was monitored by KO and KR at non-cytotoxic concentration. Surface plasmon resonance (SPR) and biolayer interferometry (BLI) analysis suggested the binding affinity and direct inhibition of KR against PD-1/PD-L1. An in silico docking simulation determined the detailed mode of binding of KR to PD-1/PD-L1. Collectively, these results suggest that KR could be developed as a potent small molecule inhibitor for PD-1/PD-L1 blockade.
Asunto(s)
Antígeno B7-H1/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Quempferoles/farmacología , Receptor de Muerte Celular Programada 1/metabolismo , Animales , Antígeno B7-H1/química , Células CHO , Cricetinae , Cricetulus , Humanos , Células Jurkat , Simulación del Acoplamiento Molecular , Receptor de Muerte Celular Programada 1/química , Unión Proteica/efectos de los fármacosRESUMEN
The chemical constituents of the Siraitia grosvenorii leaf extract were studied. Firstly, high-speed counter-current chromatography was applied to the one-step separation of four compounds from S. grosvenorii leaf extract with the solvent system composed of 0.01% acetic acid water/n-butanol/n-hexane/methanol (5:3:1:1, v/v/v/v). In this work, 270 mg of crude sample yielded four compounds, a new kaempferol O-glycoside derivative, kaempferol 3-O-α-L-[4-O-(4-carboxy-3-hydroxy-3-methylbutanoyl)]-rhamnopyranoside-7-O-α-L-rhamnopyranoside, named kaempferitrin A (2.1 mg, 90%), and three known compounds, grosvenorine (3.4 mg, 93%), kaempferitrin (14.4 mg, 99%) and afzelin (4 mg, 98%), and the structures of these compounds were identified by NMR spectroscopy and mass spectrometry. Then, ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry was used to illustrate the dominant flavonoids in S. grosvenorii leaf extract. 34 flavonoids including 19 kaempferol O-glycosides, 4 quercetin O-glycosides, 6 flavanone derivatives, and 5 polymethoxyflavones, were accurately or tentatively identified by carefully comparing their retention times, UV data, precise masses, the typical fragments of the standards and literature data. Most of these compounds were reported for the first time. This study establishes a foundation for the further development and utilization of S. grosvenorii leaves in future.
Asunto(s)
Cucurbitaceae/química , Flavonoides/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Cromatografía Líquida de Alta Presión , Distribución en Contracorriente , Flavonoides/química , Espectrometría de Masas , Estructura Molecular , Extractos Vegetales/química , Espectrometría de Masa por Ionización de Electrospray , Factores de TiempoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia forficata Link, commonly known as "cow's paw", is a native plant from South America. Its leaves are widely used in Brazilian folk medicine to treat diabetes and cardiovascular disorders. Although this species' biological potential has been extensively proven as an antidiabetic, anti-inflammatory and antioxidant agent, there is a lack of studies to evidence its action on the cardiovascular system. AIM OF THE STUDY: This study was designed to investigate the vascular effects of B. forficata leaves preparations and its majority compound kaempferitrin, as well as its aglycone form kaempferol, in rat aortic rings of normotensive (NTR) and hypertensive (SHR) rats. MATERIALS AND METHODS: Aorta rings from NTR and SHR precontracted with phenylephrine were exposed to cumulative concentrations of B. forficata extract, fractions (1-50 µg/mL) and compounds (0.001-0.3 µg/mL). The mechanisms involved in the vasorelaxant effect of ethyl-acetate plus butanol fraction (EAButF) were also evaluated. RESULTS: Although kaempferitrin is the most abundant compound found in both methanolic extract and EAButF, 24 minor phenolic compounds were identified in B. forficata leaves, including kaempferol. EAButF was the only with endothelium-dependent and independent vasorelaxant properties in both NTR and SHR. The incubation with L-NAME or ODQ completely blocked EAButF-induced vasorelaxation. On the other hand, the incubation with propranolol, atropine, indomethacin, glibenclamide or barium chloride did not change the vasorelaxant activity of EAButF (50 µg/mL). Nevertheless, the incubation with tetraethylammonium and 4-aminopyridine significantly influenced the EAButF activity. It was also shown that Ca2+ influx or efflux is not related to EAButF vasorelaxation potential. Kaempferitrin and kaempferol were also able to relax the rat aortic rings in 34.70% and 40.54%, respectively. CONCLUSIONS: This study shows, for the first time, the vasorelaxant effect of EAButF from B. forficata leaves, an effect that may be attributed to the modulation of vascular tone through nitric oxide/soluble guanylate cyclase pathway, and potassium channels. The bioactive kaempferitrin and kaempferol seem to be important for the effects observed with the fraction. Finally, preparations obtained from the leaves of B. forficata may be interesting candidates for new or complementary strategies regarding cardiovascular diseases.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Bauhinia , Hipertensión/fisiopatología , Extractos Vegetales/farmacología , Vasodilatadores/farmacología , Animales , Aorta Torácica/fisiología , Brasil , Enfermedades Cardiovasculares/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Técnicas In Vitro , Quempferoles/farmacología , Masculino , Medicina Tradicional , Óxido Nítrico/fisiología , Hojas de la Planta , Plantas Medicinales , Canales de Potasio/fisiología , Ratas Endogámicas SHR , Ratas WistarRESUMEN
Rheumatoid arthritis (RA) is a complex chronic inflammatory disease that is associated with the aberrant activation of fibroblast-like synoviocytes (FLS). Kaempferitrin is a natural flavonoid glycoside that possesses anti-inflammatory bioactivity. However, the effect of kaempferitrin on RA has not yet been revealed. The aim of the present study was to investigate the effect of kaempferitrin on human RA-FLS MH7A cell line. We found that kaempferitrin inhibited proliferation and induced apoptosis of MH7A cells. Kaempferitrin decreased the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-1, and MMP-3 in MH7A cells. Moreover, kaempferitrin blocked the activation of nuclear factor-κB (NF-κB) and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways. Furthermore, treatment with kaempferitrin decreased paw thickness and arthritis scores, and reduced the serum levels of IL-1ß, IL-6, and TNF-α in a collagen-induced arthritis mouse model. In conclusion, kaempferitrin inhibited cell proliferation, induced cell apoptosis, and ameliorated inflammation of RA-FLS by suppressing the NF-κB and Akt/mTOR pathways.