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1.
Biomed Pharmacother ; 153: 113379, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076521

RESUMO

In this experimental study, we evaluated the protective effects and the safety of main flavanones derived from Rhizoma Drynariae (Gusuibu) in vitro and in vivo. The MTT assay showed that compared with vehicle treatment, treatment with such flavanones as neoeriocitrin, naringin, and naringenin significantly promoted the viability of osteocyte-like cells. Quantitative real-time PCR showed that neoeriocitrin and naringin significantly attenuated mRNA expressions of RANKL and SOST in osteocyte-like cells. In rats with retinoic acid-induced osteoporosis, total flavonoid of Rhizoma Drynariae (TFRD), naringin, and naringenin significantly increased the number of trabeculae and improved trabecular bone structure compared with no treatment, without affecting liver and renal function. In addition, naringenin and naringin administration significantly increased bone mineral density of femur neck and femur shaft compared with the osteoporotic model rats. Western blot analysis showed that naringenin and naringin significantly attenuated protein expressions of bone resorption-related factors (TRAP, RANKL and RANK), and inhibited sclerostin expression compared with the osteoporotic model rats. On the other hand, naringin markedly increased protein expressions of ALP and PTH1R, and TFRD and naringenin also promoted PTH1R expression compared with the model rats. In conclusion, such flavanones as naringenin and naringin exhibited antiresorptive properties, and naringin particularly showed potential benefits for osteoporosis treatment.


Assuntos
Flavanonas , Osteoporose , Polypodiaceae , Animais , Flavanonas/farmacologia , Flavonoides/farmacologia , Osteócitos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Polypodiaceae/química , Ratos
2.
Biomed Res Int ; 2022: 9636436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119934

RESUMO

The galls of Pistacia integerrima are used in folk medicine for curing diabetes. The main aim of this study was the purification of flavonoids from galls of P. integerrima. The methanolic extract was subjected to column chromatographic analysis which afforded six flavonoids, namely, 3,5,7,4'-tetrahydroxy-flavanone (1), naringenin (2), 3,5,4'-trihydroxy,7-methoxy-flavanone (3), sakuranetin (4), spinacetin (5), and patuletin (6). These isolated compounds (1-6) were tested against α-glycosidase. The maximum antagonistic effect was noted against compound 6 (97.65%) followed by compound 5 (90.42%) and compound 1 (90.01%) at the same concentration (0.2 µg). The inhibitory potential of all tested compounds was significant with a degree of variation from each other. Docking studies showed that all studied compounds interact with the active site residues via hydrogen bond interactions with hydroxyl groups, and thus, inhibition was enhanced. Hence, this finding would be the first screening of isolated flavonoids for α-glycosidase activity and with the mechanism of action. These flavonoids should be further investigated as candidate drugs for combating diabetes mellitus.


Assuntos
Flavanonas , Pistacia , Flavanonas/química , Flavanonas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Glicosídeo Hidrolases , Pistacia/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia
3.
Int J Nanomedicine ; 17: 3269-3286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924260

RESUMO

Background: Naringin is a naturally occurring flavanone that promotes osteogenesis. Owing to the high lipophilicity, poor in vivo bioavailability, and extensive metabolic alteration upon administration, the clinical efficacy of naringin is understudied. Additionally, information on the molecular mechanism by which it promotes osteogenesis is limited. Methods: In this study, we prepared TAT & RGD peptide-modified naringin-loaded nanoparticles (TAT-RGD-NAR-NPs), evaluated their potency on the osteogenic differentiation of human dental pulp stem cells (hDPSCs), and studied its mechanism of action through metabolomic analysis. Results: The particle size and zeta potential of TAT-RGD-NAR-NPs were 160.70±2.05 mm and -20.77±0.47mV, respectively. The result of cell uptake assay showed that TAT-RGD-NAR-NPs could effectively enter hDPSCs. TAT-RGD-NAR-NPs had a more significant effect on cell proliferation and osteogenic differentiation promotion. Furthermore, in metabolomic analysis, naringin particles showed a strong influence on the glycerophospholipid metabolism pathway of hDPSCs. Specifically, it upregulated the expression of PLA2G3 and PLA2G1B (two isozymes of phospholipase A2, PLA2), increased the biosynthesis of lysophosphatidic acid (LPA). Conclusion: These results suggested that TAT-RGD-NPs might be used for transporting naringin to hDPSCs for modulating stem cell osteogenic differentiation. The metabolomic analysis was used for the first time to elucidate the mechanism by which naringin promotes hDPSCs osteogenesis by upregulating PLA2G3 and PLA2G1B.


Assuntos
Flavanonas , Nanopartículas , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Polpa Dentária , Flavanonas/farmacologia , Produtos do Gene tat/genética , Fosfolipases A2 do Grupo IB/metabolismo , Fosfolipases A2 do Grupo III/metabolismo , Humanos , Lipossomos , Oligopeptídeos/metabolismo , Osteogênese , Células-Tronco
4.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35955525

RESUMO

Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern 'omics' technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/ß-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.


Assuntos
Flavanonas , MicroRNAs , Neoplasias , Animais , Carcinogênese , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Camundongos , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais
5.
Biomed Pharmacother ; 154: 113563, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35987162

RESUMO

The present study aimed to recognize the recent literature to highlight the pharmacological impacts and highlight the therapeutic potential of the active molecule eriocitrin. Citrus limon are a good resource of the flavanone eriocitrin (eriodictyol 7-O-ß-D-rutinoside). Eriocitrin has potent biological actions due to its strong antioxidant, antitumor, anti-allergic, antidiabetic and anti-inflammatory activities. Eriocitrin is more potent in suppressing oxidative stress in diabetes mellitus (DM) and other chronic diseases incurred by excessive oxidative stress. During metabolism, eriocitrin is metabolized by gut microbiota, and a chain of molecules such as eriodictyol, methy-eriodictyol, 3,4-dihydroxyhydrocinnamic acid (DHCA), and much more conjugated molecules. More in-depth studies are recommended to explore this drug for clinical trials.


Assuntos
Citrus , Flavanonas , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Flavanonas/farmacologia , Estresse Oxidativo
6.
PLoS Comput Biol ; 18(7): e1010315, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35857767

RESUMO

The large conductance voltage- and Ca2+-activated K+ channels from the inner mitochondrial membrane (mitoBK) are modulated by a number of factors. Among them flavanones, including naringenin (Nar), arise as a promising group of mitoBK channel regulators from a pharmacological point of view. It is well known that in the presence of Nar the open state probability (pop) of mitoBK channels significantly increases. Nevertheless, the molecular mechanism of the mitoBK-Nar interactions remains still unrevealed. It is also not known whether the effects of naringenin administration on conformational dynamics can resemble those which are exerted by the other channel-activating stimuli. In aim to answer this question, we examine whether the dwell-time series of mitoBK channels which were obtained at different voltages and Nar concentrations (yet allowing to reach comparable pops) are discernible by means of artificial intelligence methods, including k-NN and shapelet learning. The obtained results suggest that the structural complexity of the gating dynamics is shaped both by the interaction of channel gate with the voltage sensor (VSD) and the Nar-binding site. For a majority of data one can observe stimulus-specific patterns of channel gating. Shapelet algorithm allows to obtain better prediction accuracy in most cases. Probably, because it takes into account the complexity of local features of a given signal. About 30% of the analyzed time series do not sufficiently differ to unambiguously distinguish them from each other, which can be interpreted in terms of the existence of the common features of mitoBK channel gating regardless of the type of activating stimulus. There exist long-range mutual interactions between VSD and the Nar-coordination site that are responsible for higher levels of Nar-activation (Δpop) at deeply depolarized membranes. These intra-sensor interactions are anticipated to have an allosteric nature.


Assuntos
Flavanonas , Canais de Potássio Cálcio-Ativados , Inteligência Artificial , Cálcio/metabolismo , Flavanonas/farmacologia , Aprendizado de Máquina
7.
Redox Rep ; 27(1): 158-166, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35861275

RESUMO

BACKGROUND: Methotrexate (MTX) is a commonly used chemotherapeutic drug that has adverse toxic effects on germ cells. Naringin (NG) is a natural flavanone glycoside, with different phytotherapeutic applications, and its possible protective effects against MTX-induced testicular tissue damage were investigated in this study. METHODS: Low and high doses of NG (40 and 80 mg/kg/day) were given for 10 days by intraperitoneal (i.p.) injection and MTX (20 mg/kg i.p.) was given at the 4th day of the experiment, with or without NG in rats. RESULTS: The obtained results showed that exposure to MTX increased malondialdehyde (MDA) levels and nitric oxide (NO) production compared with the control. In the meantime, MTX depleted catalse (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the testicular tissue. Further, serum testosterone levels were significantly decreased in the MTX group. NG significantly counteracted the aforementioned effects of MTX; however, NG80 was more effective in restoring SOD, GR, MDA and NO. Interestingly, NG80 achieved a better improvement in the ultrastructural pattern of the testicular cells in MTX-exposed rats. CONCLUSION: These results indicated, for the first time, that NG could be a potential candidate therapy against MTX-reprotoxic impacts.


Assuntos
Flavanonas , Metotrexato , Animais , Antioxidantes/metabolismo , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Masculino , Metotrexato/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Testículo/metabolismo
8.
Life Sci ; 305: 120752, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35779626

RESUMO

Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies show the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anti-cancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/ß-catenin, PI3K/Akt, NF-ĸB, and TGF-ß pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.


Assuntos
Carcinoma de Células Escamosas , Flavanonas , Neoplasias Bucais , Carcinoma de Células Escamosas/tratamento farmacológico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides , Humanos , Masculino , Neoplasias Bucais/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
9.
Int J Mol Sci ; 23(13)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35806375

RESUMO

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1-100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP.


Assuntos
Oftalmopatias , Flavanonas , Animais , Humor Aquoso/metabolismo , Oftalmopatias/metabolismo , Flavanonas/metabolismo , Flavanonas/farmacologia , Pressão Intraocular , Camundongos , Cadeias Leves de Miosina/metabolismo , Malha Trabecular/metabolismo
10.
Biomed Pharmacother ; 151: 113191, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35643068

RESUMO

Pulmonary hypertension (PH) is a chronic and fatal disease, for which new therapeutic drugs and approaches are needed urgently. Baicalein and baicalin, the active compounds of the traditional Chinese medicine, Scutellaria baicalensis Georgi, exhibit a wide range of pharmacological activities. Numerous studies involving in vitro and in vivo models of PH have revealed that the treatment with baicalin and baicalein may be effective. This review summarizes the potential mechanisms driving the beneficial effects of baicalin and baicalein treatment on PH, including anti-inflammatory response, inhibition of pulmonary smooth muscle cell proliferation and endothelial-to-mesenchymal transformation, stabilization of the extracellular matrix, and mitigation of oxidative stress. The pharmacokinetics of these compounds have also been reviewed. The therapeutic potential of baicalin and baicalein warrants their continued study as natural treatments for PH.


Assuntos
Flavanonas , Hipertensão Pulmonar , Flavanonas/química , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Hipertensão Pulmonar/tratamento farmacológico
11.
Am J Chin Med ; 50(5): 1255-1267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35748215

RESUMO

Preconditioning has a powerful protective potential against myocardial ischemia-reperfusion injury (I/R). Our prior work demonstrated that baicalein, a flavonoid derived from the root of Scatellaria baicalensis Georgi (also known as Huangqin), confers this preconditioning protection. This study further explored the mechanisms of baicalein preconditioning (BC-PC) in mouse cardiomyocytes. Cells were treated with baicalein (10 µM) for a brief period of time (10 min) prior to simulated ischemia 90 min/reperfusion for 180 min. Baicalein triggered an induction of a small amount of mitochondrial reactive oxygen species (ROS) prior to the initiation of ischemia, assessed by 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate (6-carboxy-H2DCFDA). It also significantly increased cell viability measured by propidium iodide (PI) and lactate dehydrogenase and preserved mitochondrial membrane potential assessed by TMRM fluorescence intensity. Myxothiazol, a mitochondrial electron transport chain complex III inhibitor, partially blocked ROS generation induced by BC-PC and reduced cell viability. BC-PC increased phosphorylation of Akt (Thr308 and Ser473) and eNOS Ser1177, and nitric oxide (NO) production measured using 4,5-diaminofluorescein diacetate (DAF-2 DA, 1 µM). Akt inhibitor API-2 abolished Akt phosphorylation and reduced DAF-2 production and cell viability. In addition, BC-PC decreased phosphorylation of pyruvate dehydrogenase (PDH) reflecting upregulated PDH activity, and increased ATP production at 30 min during reperfusion. Taken together, baicalein preconditioning-induced cardioprotection involves pro-oxidant generation, activates survival signaling Akt/eNOS/NO, and improves metabolic recovery after I/R injury. Our work provides new perspectives on the effect of baicalein on cardiac preconditioning against I/R injury.


Assuntos
Flavanonas , Proteínas Proto-Oncogênicas c-akt , Animais , Flavanonas/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piruvatos , Espécies Reativas de Oxigênio/metabolismo
12.
Ars pharm ; 63(2)abr.-jun. 2022. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-202812

RESUMO

Introduction: Urothelial carcinoma is a significant public health problem. Transitional cell carcinoma (TCC) is the most common subtype, accounting for approximately 90 % of all bladder cancers. Chemotherapeutic protocols have been studied, but some present high toxicity and low tolerability. Naringin is a polyphenolic compound found mainly in citrus fruits, which antitumor activity has been studied in several types of cancer. However, there is little information about naringin effects on bladder cancer. This study aimed to evaluate the antitumor potential of naringin in silico and in vitro using two bladder cancer cell lines. Method: In silico analysis was carried out by PASS Online software. In vitro , the effects of naringin treatment (12.5 - 400 µM) were evaluated regarding its cytotoxicity, clonogenic survival, morphological alterations, cell cycle progression, migration, and mutagenicity Results: In silico analyses predicted antitumor activity through several mechanisms of action. In vitro results showed naringin presented cytotoxic effects, reduced the number of colonies, inhibited cell migration, and changed the morphology and cell cycle progression of the two cell lines evaluated. However, naringin did not present mutagenic effects. Conclusions: Naringin has antiproliferative activity and is a promising candidate for bladder cancer treatment.(AU)


Introducción: El carcinoma urotelial es un problema de salud pública importante. El carcinoma de células de transición es el subtipo más común y representa aproximadamente el 90 % de todos los cánceres de vejiga. Se han estudiado protocolos quimioterapéuticos, pero algunos presentan alta toxicidad y baja tolerabilidad. La naringina es un compuesto polifenólico que se encuentra principalmente en los cítricos, cuya actividad antitumoral se ha estudiado en varios tipos de cáncer. Sin embargo, hay poca información sobre los efectos de la naringina en el cáncer de vejiga. Este estudio tuvo como objetivo evaluar el potencial antitumoral de la naringina in silico e in vitro utilizando dos líneas celulares de cáncer de vejiga. Método: El análisis in silico se llevó a cabo mediante el software PASS Online. In vitro, se evaluaron los efectos del tratamiento con naringina (12,5 - 400 µM) en cuanto a su citotoxicidad, supervivencia clonogénica, alteraciones morfológicas, progresión del ciclo celular, migración y mutagenicidad. Resultados: los análisis in silico predijeron la actividad antitumoral a través de varios mecanismos de acción. Los resultados in vitro mostraron que la naringina presentó efectos citotóxicos, redujo el número de colonias, inhibió la migración celular y cambió la morfología y la progresión del ciclo celular de las dos líneas celulares evaluadas. Sin embargo, la naringina no presentó efectos mutagénicos. Conclusiones: la naringina tiene actividad antiproliferativa y es un candidato prometedor para el tratamiento del cáncer de vejiga.(AU)


Assuntos
Humanos , Compostos de Silício/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Bexiga Urinária , Flavanonas/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos
13.
Int J Biol Macromol ; 213: 944-954, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35690164

RESUMO

Cancer is one of the major causes of global deaths and needs immediate therapeutic development. So far, several strategies have been undertaken to prevent cancer, including kinase targeting by small-molecule inhibitors. Cyclin dependent kinase 6 (CDK6) plays an essential role in cancer progression and development as its overexpression is associated with tumor development and progression. The present study demonstrated that Naringenin (NAG) binds strongly to CDK6 with a binding affinity of -7.51 kcal/mol. ATPase assay of CDK6 in the presence of NAG shows that it inhibits CDK6 with an IC50 = 3.13 µM. Fluorescence and isothermal titration calorimetry studies demonstrated that NAG binds to CDK6 with the binding constant (K) values of 3.55 × 106 M-1 and 7.06 ± 2.70 × 106 M-1, respectively. The cell-based functional studies showed that NAG decreases the cell viability of human cancer cell lines, induces apoptosis, and reduces their colonization ability. Outcomes of the present in silico and in vitro studies highlighted the significance of NAG for the development of anti-cancer leads in terms of CDK6 inhibitors and provided future implications for combinatorial anti-cancer therapies.


Assuntos
Quinase 6 Dependente de Ciclina , Flavanonas , Neoplasias , Apoptose/efeitos dos fármacos , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/química , Quinase 6 Dependente de Ciclina/metabolismo , Flavanonas/química , Flavanonas/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/metabolismo , Neoplasias/patologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
14.
Molecules ; 27(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35744861

RESUMO

Naringenin (NRG) is a natural compound with several biological activities; however, its bioavailability is limited owing to poor aqueous solubility. In this study, NRG nanoparticles (NPs) were prepared using the wet media milling method. To obtain NRG NPs with a small particle size and high drug-loading content, the preparation conditions, including stirring time, temperature, stirring speed, and milling media amount, were optimized. The NRG (30 mg) and D-α-tocopherol polyethylene glycol succinate (10 mg) were wet-milled in deionized water (2 mL) with 10 g of zirconia beads via stirring at 50 °C for 2 h at a stirring speed of 300 rpm. As a result, the NRG NPs, with sheet-like morphology and a diameter of approximately 182.2 nm, were successfully prepared. The NRG NPs were stable in the gastrointestinal system and were released effectively after entering the blood circulation. In vivo experiments indicated that the NRG NPs have good antitussive effects. The cough inhibition rate after the administration of the NRG NPs was 66.7%, cough frequency was three times lower, and the potential period was 1.8 times longer than that in the blank model group. In addition, the enzyme biomarkers and histological analysis results revealed that the NRG NPs can effectively regulate the inflammatory and oxidative stress response. In conclusion, the NRG NPs exhibited good oral bioavailability and promoted antitussive and anti-inflammatory effects.


Assuntos
Antitussígenos , Flavanonas , Nanopartículas , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Tosse/tratamento farmacológico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Humanos , Tamanho da Partícula , Solubilidade , Água
16.
Eur Rev Med Pharmacol Sci ; 26(10): 3419-3429, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35647821

RESUMO

OBJECTIVE: Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a plasticizer in many products, including plastics, cosmetics, and medical devices. Naringenin (NAR) is a flavonoid belonging to the flavanones subclass. It is widely distributed in several citrus fruits, bergamot, tomatoes, and other fruits. It is also found in its glycoside form (mainly naringin). Several biological activities have been ascribed to this phytochemical: antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. This study hypothesized that phthalates' possible reproductive damage mechanism is oxidative attack, and naringenin could have a protective effect against radical forms in the body through its antioxidant properties. MATERIALS AND METHODS: Thirty-two male rats were used in our study (n=8 each). Rats were randomly divided into four groups: Control, DBP, DBP +NAR and NAR. Phthalate (DBP) and NAR were administered through gastric oral gavage (phthalate group 500 mg/kg/day DBP; NAR group 50 mg/kg/day NAR). At the end of four weeks, testis tissue samples were taken under anesthesia. Testis tissue and blood samples were collected from the four groups in this study. Histological, biochemical and spermatological analyses were conducted. RESULTS: Tissue samples from the control and NAR groups showed normal histological appearance on light microscopy. The DBP group exhibited deterioration in seminiferous tubules, vascular congestion in capsule, vascular congestion between the seminiferous tubules, edema in the intestinal area and vacuolization, arrested spermatocytes in different stages of division; sloughing of cells into the seminiferous tubular lumen was observed. It was also observed that NAR treatment significantly inhibited and prevented the histopathological damage caused by DBP. Tissue TBARS, antioxidant parameters, sperm motility, sperm density and abnormal spermatozoon ratios were determined. As a result, it was shown that DBP caused oxidative damage by increasing TBARS levels and decreasing antioxidant parameters, increased abnormal sperm rate and decreased sperm motility, and concentration and histopathological damage, so the antioxidant activity of naringenin inhibited this damage. CONCLUSIONS: DBP had toxic effects in rat testis tissue; NAR treatment ameliorated these effects. Further studies are warranted to confirm our findings.


Assuntos
Flavanonas , Motilidade Espermática , Animais , Antioxidantes/farmacologia , Dibutilftalato/toxicidade , Flavanonas/farmacologia , Masculino , Ácidos Ftálicos , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/farmacologia
17.
Phytomedicine ; 102: 154159, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35580441

RESUMO

BACKGROUND: Eriodictyol in citrus fruits, Eriodictyon californicum and several Chinese herbal medicines shows great promise for chronic disease prevention, including cancers. However, its role in chemopreventive activities against breast carcinogenesis is unknown. PURPOSE: In the present study, we investigated the chemopreventive effect and the underlying mechanism of eriodictyol on carcinogens-induced breast carcinogenesis in vivo and in vitro. METHODS: The carcinogenic transformation in MCF10A cells was induced by the environmental carcinogens in vitro. The chemopreventive effect in vivo was evaluated by using the experimental model of 1-methyl-1-nitrosourea (MNU)-induced mammary tumorigenesis in rats. The activation of the PI3K/Akt pathway was detected by western blot assay; the levels of circular RNAs (circRNAs) were measured by qRT-PCR. RESULTS: First, eriodictyol significantly reduces cells viability and induces apoptosis in breast cancer cells in a dose-dependent manner in vitro (P < 0.05). Next, eriodictyol could effectively suppress environmental carcinogens-induced acquisition of carcinogenic properties in human breast epithelial cell MCF10A (P < 0.05). In vivo, eriodictyol administration reduces the incidence of mammary tumor by 50% in carcinogen-treated female rats (P < 0.05). Further study revealed that eriodictyol represses the PI3K/Akt signaling pathway and down-regulates the level of circ_0007503 in breast cancer cells and in breast carcinogenesis (P < 0.01). When the effect of eriodictyol on circ_0007503 was blocked by transfection of a circ_0007503 over-expression plasmid, the cytotoxic effects and the suppression of the PI3K/Akt pathway of eriodictyol in breast cancer cells were significantly reduced (P < 0.05). CONCLUSION: Our data indicated that eriodictyol could effectively suppress breast carcinogenesis in vitro and in vivoThe mechanism may be attributed to targeting circ_0007503 and inhibiting PI3K/Akt pathway.


Assuntos
Neoplasias da Mama , Flavanonas , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinógenos Ambientais/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/efeitos dos fármacos , Feminino , Flavanonas/farmacologia , Humanos , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
18.
Appl Biochem Biotechnol ; 194(9): 4220-4243, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35567708

RESUMO

Cancer is a global burden and mechanistically complex disease with a plethora of genetic, physiological, metabolic, and environmental alterations. The development of dietary nutraceuticals into cancer chemotherapeutics has emerged as a new paradigm in cancer treatment. Alpinetin (ALPI) is a novel flavonoid component of multiple edible and medicinal plants and possesses a wide range of biological and pharmacological activities including antibacterial, anti-hemostatic, anti-oxidative, anti-hepatotoxic, stomachic, immunosuppressive, and anti-inflammatory. Recently, ALPI has been reported as a bioactive dietary nutraceutical with promising anticancer activity in various human cancers through multiple mechanisms. The purpose of this review is to compile the data on natural sources of ALPI, and its anticancer activity including cellular targets and anticancer mechanism in various human cancers. Moreover, this review will set the stage for further design and conduct pre-clinical and clinical trials to develop ALPI into a lead structure for oncological therapy.


Assuntos
Flavanonas , Neoplasias , Anti-Inflamatórios , Flavanonas/química , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Polifenóis
19.
Colloids Surf B Biointerfaces ; 216: 112515, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35512464

RESUMO

Wogonin (Wog) plays an important role in human diseases, especially cancer and inflammatory diseases, but its poor solubility, unstable metabolism and low bioavailability greatly limit its application in biomedical fields. Therefore, we developed a temperature-dependent method to encapsulate wogonin into a novel ferritin-based nanocarrier. To improve the loading capacity and stability, the human H chain ferritin (HFtn) was functionalized with a repetitive polypeptide sequence composed of proline (Pro), alanine (Ala), and serine (Ser) in different residues lengths (PAS10 and PAS30). Wogonin loading and release studies demonstrated that the encapsulation efficiency and stability of the PASylated nanocarriers were significantly higher than those of the wild type. PAS-HFtn-Wog exhibited enhanced cytotoxicity to MCF-7 breast cancer cells and HepG2 liver cancer cells. Notably, the PASylated HFtn, especially PAS30-HFtn greatly prolonged the pharmacokinetics of wogonin in the mice bloodstream. Therefore, wogonin-loaded PAS-HFtn may be a promising drug candidate for cancer therapy.


Assuntos
Ferritinas , Flavanonas , Animais , Apoferritinas , Flavanonas/química , Flavanonas/farmacologia , Humanos , Células MCF-7 , Camundongos
20.
Biomolecules ; 12(5)2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35625554

RESUMO

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.


Assuntos
Citrus , Flavanonas , Hesperidina , Osteoporose , Densidade Óssea , Citrus/química , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Hesperidina/análogos & derivados , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Osteoporose/tratamento farmacológico
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