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1.
PLoS One ; 17(9): e0274915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36126078

RESUMO

BACKGROUND: Wheat (Triticum aestivum L.) is a major food crop worldwide. Low soil phosphorus content and drought are the main constraints on wheat production in Xinjiang, China. METHODS: In this study, the ionic and metabolic responses of one wheat variety ("Xindong20") to drought stress simulated by using polyethylene glycol 6000 (PEG-6000) were investigated under low phosphorus (LP) and conventional phosphorus (CP) conditions by analysing wheat mineral elements and metabolites. Besides, due to xanthohumol was the metabolite with the most significant difference in expression detected in "Xindong 20", two wheat variety "Xindong20 and Xindong 23" were selected to conduct the germination test simultaneously, to further verify the function of xanthohumol in wheat growth. Xanthohumol was mixed with PEG solution (20%) to prepare PEG solutions with different concentrations (0%, 0.1%, 0.5%, and 1%) of xanthohumol. Then wheat grains were soaked in the solutions for 20 hours, followed by a germination test. After 7 days, the indicators including shoot length, max root length, and root number were determined to identify whether the metabolite was beneficial to improve the drought tolerance of wheat. RESULTS: The results showed that the root density and volume of wheat in LP treatment were higher than those in CP treatment. The roots underwent programmed cell death both in LP and CP treatments under PEG-6000-simulated drought stress, however, the DNA degradation in root cells in LP treatment was lower than that in CP treatment after rehydration for 3 d. Before drought stress, the malondialdehyde (MDA) content in shoot and the peroxidase (POD) activity in root in LP treatment were significantly higher than those in CP treatment, while the soluble sugar content and chlorophyll content in LP treatment were significantly lower than those in CP treatment. During drought stress, the POD activity maintained at a high level and the soluble sugar content gradually increased in LP treatment. After rehydration, the MDA content still maintained at a high level in LP treatment, the superoxide dismutase (SOD) activity increased, and the contents of soluble sugar and chlorophyll were significantly higher than those in CP treatment. The analysis of mineral elements and metabolites showed that the wheat in CP treatment was more sensitive to drought stress than that in LP treatment. Besides, the effect of drought stress was greater on shoot than on root in CP treatment, while it was opposite in LP treatment. The effect of drought stress on sugar metabolism gradually increased. Germination assays showed that 0.1% exogenous xanthohumol addition could significantly increase the shoot length of the two wheat varieties under drought stress. CONCLUSION: Appropriate low phosphorus supply could increase antioxidant enzyme activity in wheat, and enhance sugar metabolism to regulate osmotic balance, as well as the accumulation of various organic acids to maintain the intracellular ion homeostasis. Therefore, compared to the conventional phosphorus supply level, appropriate low phosphorus supply can significantly improve the drought tolerance of wheat. Additionally, addition of 0.1% exogenous xanthohumol, an important differential expressed metabolite in drought-stressed wheat, could effectively promote wheat shoot growth under drought stress.


Assuntos
Secas , Plântula , Antioxidantes/metabolismo , Clorofila/metabolismo , DNA/metabolismo , Flavonoides , Malondialdeído/metabolismo , Peroxidases/metabolismo , Fósforo/metabolismo , Polietilenoglicóis , Propiofenonas , Solo , Açúcares/metabolismo , Superóxido Dismutase/metabolismo , Triticum/genética
2.
Sci Rep ; 12(1): 14970, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056072

RESUMO

Xanthohumol (XN) is a prenylated plant polyphenol that naturally occurs in hops and its products, e.g. beer. It has shown to have anti-inflammatory and angiogenesis inhibiting effects and it prevents the proliferation of cancer cells. These effects could be in particular interesting for processes within the periodontal ligament, as previous studies have shown that orthodontic tooth movement is associated with a sterile inflammatory reaction. Based on this, the study evaluates the anti-inflammatory effect of XN in cementoblasts in an in vitro model of the early phase of orthodontic tooth movement by compressive stimulation. XN shows a concentration-dependent influence on cell viability. Low concentrations between 0.2 and 0.8 µM increase viability, while high concentrations between 4 and 8 µM cause a significant decrease in viability. Compressive force induces an upregulation of pro-inflammatory gene (Il-6, Cox2, Vegfa) and protein (IL-6) expression. XN significantly reduces compression related IL-6 protein and gene expression. Furthermore, the expression of phosphorylated ERK and AKT under compression was upregulated while XN re-established the expression to a level similar to control. Accordingly, we demonstrated a selective anti-inflammatory effect of XN in cementoblasts. Our findings provide the base for further examination of XN in modulation of inflammation during orthodontic therapy and treatment of periodontitis.


Assuntos
Cemento Dentário , Propiofenonas , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Humanos , Inflamação/tratamento farmacológico , Interleucina-6 , Propiofenonas/farmacologia
3.
Malawi Med J ; 34(2): 87-94, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35991818

RESUMO

Background: Perinatal depression is a common and disabling mental health problem in Malawi and other Low- and middle-income countries. There is evidence for effective psychosocial interventions for perinatal depression, but no such intervention has been developed for use in Malawi. The broad aim of this study was to explore the cultural appropriateness of a psychosocial intervention for perinatal depression called the Thinking Healthy Programme-Peer delivered for adaptation and use in Lilongwe, Malawi. Methods: A qualitative exploratory design was used. Data were collected through conducting five Focus Group Discussions, involving thirty-eight purposefully selected participants including pregnant women, community volunteers and their supervisors, the Health Surveillance Assistants and maternal health care workers at implementation and policy level following observations of video recorded role plays of the Thinking Healthy Programme-Peer delivered sessions in theatre testing. A content analysis approach was used to analyse data. Results: Six main themes were generated regarding the appropriateness of the content and delivery of the Thinking Healthy Programme-Peer delivered intervention, including: 1) Focus of the intervention; 2) Cultural appropriateness of the content; 3) Language used; 4) Context; 5) Provider of the intervention; and 6) Flexibility in the delivery of the intervention. The Thinking Healthy Programme-Peer delivered intervention was deemed appropriate for the target population, though with recommendations to: review illustrations to enhance clarity, use culturally appropriate stories and idioms, use daily spoken language, and adapt the number and duration of sessions to meet the needs of individual clients. Conclusions: These findings highlight important areas to inform adaptation of the Thinking Healthy Programme-Peer delivered and add to the growing evidence of cultural adaptation of psychosocial interventions for perinatal depression.


Assuntos
Depressão , Intervenção Psicossocial , Depressão/psicologia , Depressão/terapia , Feminino , Humanos , Malaui , Grupo Associado , Gravidez , Propiofenonas
4.
Molecules ; 27(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35956774

RESUMO

Herein, we propose two chalcone molecules, (E)-1-(4-methoxyphenyl)-3-(p-tolyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) prop-2-en-1-one, based on the anticancer bioactive molecule Xanthohumol, which are suitable for further in vitro and in vivo studies. Their ability to create stable complexes with the antiapoptotic X-linked IAP (XIAP) protein makes them promising anticancer agents. The calculations were based on ligand-based and structure-based virtual screening combined with the pharmacophore build. Additionally, the structures passed Lipinski's rule for drug use, and their reactivity was confirmed using density functional theory studies. ADMET studies were also performed to reveal the pharmacokinetic potential of the compounds. The candidates were chosen from 10,639,400 compounds, and the docking protocols were evaluated using molecular dynamics simulations.


Assuntos
Proteínas Reguladoras de Apoptose , Propiofenonas , Flavonoides , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Propiofenonas/farmacologia
5.
Environ Pollut ; 312: 119987, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35995291

RESUMO

Avobenzone (AVO) is one of the most frequent ultraviolet (UV) filters in personal care products (PCPs). The Mediterranean mussel Mytilus galloprovincialis is a bioindicator often used for ecotoxicological research. Since UV filters reach higher peaks during summer in aquatic bodies, coincident with mussels' spawning period, and bivalves are sessile, both male gametes and adults of this species were used in this experiment. Therefore, the present study aimed to assess how AVO affects M. galloprovincialis at different biological levels. In vitro experiments on sperms (30 min-exposure) and in vivo experiments on adults (28 days-exposure) were carried out at 0.1, 1.0 and 10.0 µg/L of AVO concentrations. The oxidative and physiological status together with genotoxicity in exposed sperms were assessed. Several biochemical parameters related to enzymatic antioxidant defences, biotransformation enzymes, cell membrane damage, energy reserves, and neurotoxicity were evaluated in adult mussels. Results of in vitro sperm exposure to AVO showed significant overproduction of superoxide anions and DNA damages in all treatments and decrease in sperm viability at 1.0 and 10.0 µg/L. AVO exposure also led to complete inhibition of motility of sperms at the highest concentration, while a significant increase of curvilinear velocity and decrease of wobble occurred at 1.0 µg/L. In vivo exposed adults exhibited a significant decrease in metabolic capacity at 0.1 µg/L, a significant increase in the total protein content and enzymatic turnover as superoxide dismutase (antioxidant defence) at 10 µg/L. This study revealed an ecological concern related to the high sensitivity of sperms respectively to adults under environmentally relevant concentrations of AVO, underpinning an hypothesis of male reproductive function impairments.


Assuntos
Mytilus , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Biomarcadores Ambientais , Masculino , Mytilus/metabolismo , Estresse Oxidativo , Propiofenonas , Sêmen/metabolismo , Protetores Solares/metabolismo , Protetores Solares/toxicidade , Superóxido Dismutase/metabolismo , Superóxidos , Poluentes Químicos da Água/análise
6.
Environ Sci Technol ; 56(14): 10249-10257, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35793412

RESUMO

Previous wastewater-based epidemiology studies on methcathinone (MC), a controlled substance in many countries, attributed its occurrence in wastewater to its misuse. However, such attribution did not consider the possibility that MC may also come from the transformation of ephedrine (EPH) and pseudo-ephedrine (PEPH). In this work, EPH/PEPH and MC in wastewater of six major Chinese cities were systematically examined. EPH/PEPH concentrations in all the cities showed clear seasonal variations, with maximum and minimum concentrations observed in winter and summer, respectively. In contrast, MC concentrations were the lowest in winter, leading to minimum concentration ratios between MC and EPH/PEPH in winter. Lack of MC seizure in the cities suggests that MC abuse could not account for the ubiquitous detection of the substance in the wastewater of these cities. Batch experiments confirmed EPH/PEPH transformation into MC in wastewater. The significantly lower transformation rate at a lower temperature was consistent with low MC concentrations in winter. These results indicate that when monitoring MC through wastewater, EPH/PEPH concentrations must be determined simultaneously to avoid false identification of MC abuse. The observed ratios of MC to EPH/PEPH concentrations in this work may be used to determine MC abuse. Alternatively, other biomarkers (e.g., cathinone) may be considered to avoid interference from EPH/PEPH transformation.


Assuntos
Propiofenonas , Águas Residuárias , Efedrina , Pseudoefedrina
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121652, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-35907314

RESUMO

Fish skin collagen films are widely used as adhesives in medicine and cosmetology. Ultraviolet (UV) irradiation can be considered as an effective sterilization method for biomaterials, however, it may also lead to material photodegradation. In this work, the influence of xanthohumol and propanediol on the physico-chemical properties of collagen films before and after UV irradiation was studied. Collagen for this research was extracted from silver carp skin and thin films were fabricated by the solution casting methods. The structure of films was researched using infrared spectroscopy. The surface properties of films were investigated using Atomic Force Microscopy (AFM) and contact angle measurements. Mechanical properties were measured as well. It was found that the addition of xanthohumol and propanediol modified the roughness of collagen films and their mechanical properties. UV irradiation led to the water loss from the film and modification of the collagen structure. In the presence of propanediol and xanthohumol the water loss after UV irradiation was smaller than in UV-irradiated collagen films without these additives.


Assuntos
Colágeno , Raios Ultravioleta , Animais , Colágeno/química , Flavonoides , Microscopia de Força Atômica , Propiofenonas , Propilenoglicóis , Água
8.
Talanta ; 249: 123663, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704956

RESUMO

Methcathinone (MC), a new and easily abused psychoactive substance, not only has a rigorous impact on public security, but also endangers people's health. Herein, novel fluorescent europium metal-organic frameworks (Eu-MOF) were synthesized through a facile one-step solvothermal strategy and utilized as an effective "signal-off" sensing platform for rapid and ultrasensitive detection of MC. The as-fabricated Eu-MOF possessed superior optical properties encompassing bright red fluorescence and good photostability. In the presence of MC, the fluorescence of Eu-MOF was significantly quenched, mainly attributing to the internal filtering effect between Eu-MOF and MC. The fluorescent signal showed high selectivity for MC over other illicit drugs, and offered two linear ranges of 1-100 ng/mL and 100-4000 ng/mL with a detection limit of 0.40 ng/mL. Strikingly, the nanoprobe could be applied for the assay of MC in human urine with satisfactory recoveries and acceptable results. This work provides a promising route for MC detection to effectively control illicit drug pandemic worldwide.


Assuntos
Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Propiofenonas , Európio , Corantes Fluorescentes , Humanos
10.
Nutr Cancer ; 74(9): 3413-3430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35594207

RESUMO

Breast cancer constitutes the most incident cancer and one of the most common causes of cancer-related death. "Glutamine addiction", an important metabolic feature of cancer cells, is dependent on supply of this amino acid from external sources. In this study, the effect of several polyphenols (catechin, epicatechin, EGCG, catechin:lysine, naringenin, hesperidin, malvidin, delphinidin, kaempferol, quercetin, rutin, myricetin, resveratrol, xanthohumol, and chrysin) upon glutamine (3H-GLN) uptake by human breast epithelial adenocarcinoma cell lines with distinct characteristics (MCF-7 and MDA-MB-231) was assessed.Several polyphenols interfere with 3H-GLN uptake by both cell lines. Xanthohumol markedly decreases total and Na+-dependent 3H-GLN uptake and showed a cytotoxic and anti-proliferative effect in MDA-MB-231 cells. Xanthohumol is as an uncompetitive inhibitor of Na+-dependent 3H-GLN uptake and inhibits GPNA (L-γ-glutamyl-p-nitroanilide)-sensitive, both ASCT2 (alanine, serine, cysteine transporter 2)-mediated and non-ASCT2-mediated 3H-GLN uptake. Xanthohumol does not interfere with the transcription rates of ASCT2. The cytotoxic effect of xanthohumol, but not its anti-proliferative effect, is GPNA-sensitive and related to ASCT2 inhibition. Combination of xanthohumol with the breast cancer chemotherapeutic agent doxorubicin results in an additive anti-proliferative, but not cytotoxic effect.We conclude that targeting glutamine uptake might constitute a potential interesting strategy for triple-negative breast cancer.


Assuntos
Antineoplásicos , Catequina , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Flavonoides , Glutamina/metabolismo , Glutamina/farmacologia , Humanos , Polifenóis , Propiofenonas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
11.
Nat Commun ; 13(1): 2795, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35589741

RESUMO

Skin diseases are common human illnesses that occur in all cultures, at all ages, and affect between 30% and 70% of individuals globally. TRPV3 is a cation-permeable TRP channel predominantly expressed in skin keratinocytes, implicated in cutaneous sensation and associated with numerous skin diseases. TRPV3 is inhibited by the local anesthetic dyclonine, traditionally used for topical applications to relieve pain and itch. However, the structural basis of TRPV3 inhibition by dyclonine has remained elusive. Here we present a cryo-EM structure of a TRPV3-dyclonine complex that reveals binding of the inhibitor in the portals which connect the membrane environment surrounding the channel to the central cavity of the channel pore. We propose a mechanism of TRPV3 inhibition in which dyclonine molecules stick out into the channel pore, creating a barrier for ion conductance. The allosteric binding site of dyclonine can serve as a template for the design of new TRPV3-targeting drugs.


Assuntos
Queratinócitos , Canais de Cátion TRPV , Anestésicos Locais , Humanos , Queratinócitos/metabolismo , Propiofenonas , Pele/metabolismo , Canais de Cátion TRPV/metabolismo
12.
Ecotoxicology ; 31(6): 948-955, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35622199

RESUMO

Avobenzone and octinoxate are frequently used as organic ultraviolet filters, and these chemicals are widely detected in water. This study evaluated the potential of avobenzone and octinoxate to disrupt thyroid endocrine system in wild-type and thyroid hormone receptor alpha a knockout (thrαa-/-) zebrafish embryo/larvae. Following a 120 h exposure to various concentrations of avobenzone and octinoxate, larvae mortality and developmental toxicity in wild-type and thrαa-/- fish were assessed. Triiodothyronine (T3) and thyroxine (T4) levels as well as transcriptional levels of ten genes associated with the hypothalamus-pituitary-thyroid (HPT) axis were measured in wild-type fish. Significantly lower larvae survival rate in thrαa-/- fish exposed to ≥3 µM avobenzone and octinoxate suggests that the thyroid hormone receptor plays a crucial role in the toxic effects of avobenzone and octinoxate. A significant increase in the deio2 gene level in avobenzone-exposed zebrafish supports the result of an increased ratio of T3 to T4. Significant decrease of T4 level with upregulation of trh, tshß, and tshr genes indicates feedback in the hypothalamus and pituitary gland to maintain hormonal homeostasis. Our observation indicates that exposure to avobenzone and octinoxate affects the thyroid hormone receptor and the feedback mechanisms of the HPT axis. CLINICAL TRIALS REGISTRATION: Not applicable.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Cinamatos , Disruptores Endócrinos/toxicidade , Sistema Endócrino , Larva , Propiofenonas , Receptores dos Hormônios Tireóideos/genética , Glândula Tireoide , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia
13.
Sci Total Environ ; 836: 155696, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35525340

RESUMO

Methcathinone is a prevalent Novel Psychoactive Substance (NPS) used illicitly in some countries. Routine analysis of wastewater sampled from catchments in South Australia has shown a consistent low-level presence of the compound, inconsistent with NPS use. This raised the question was the occurrence due to regular use as a drug of choice or was it an artefact being produced from other sources in the sewer system? NPS consumption is generally sporadic and would therefore point to the origin of methcathinone in wastewater being due to in-sewer oxidation of its legal precursor, pseudoephedrine. The present study tested this hypothesis by comparing the levels of pseudoephedrine and methcathinone in wastewater samples collected bimonthly from 8 catchment sites in South Australia. Laboratory experiments exposing pseudoephedrine to common household oxidizing agents (hypochlorite and percarbonate) were also performed and the production of methcathinone was demonstrated and monitored. The results of this study showed that the level of pseudoephedrine and methcathinone measured in wastewater followed a similar pattern. However, there were periods when the levels of each compound diverged. Laboratory experiments showed that when exposed to various oxidizing agents, pseudoephedrine is oxidised to non-stoichiometric quantities of methcathinone. Although the use of methcathinone as a drug of choice remains possible, the results of this study indicate that the low and persistent level of methcathinone found in wastewater may arise in part from the oxidation of pseudoephedrine in the sewer system.


Assuntos
Pseudoefedrina , Águas Residuárias , Artefatos , Oxidantes , Propiofenonas , Águas Residuárias/análise
14.
Prog Biophys Mol Biol ; 172: 3-14, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405185

RESUMO

Today, there is a growing interest nowadays in the use of herbal substances as cancer therapeutic agents. Over recent years, Xanthohumol (XTL) has been brought out as a prenylated chalcone that is found in hops (Humulus lupulus) and beer. XTL is being investigated for its potential properties, and it has been found to have various biological effects, including anti-microbial, anti-viral, and immunomodulatory. Other than these biological effects, it has also been found that XTL exerts anti-tumor effects. In the beginning, XTL, by modulating cell signaling pathways, including ERK, AKT, NF-κB, AMPK, Wnt/ß-catenin, and Notch signaling in cancer cells, inhibits tumor cell functions. Moreover, XTL, by inducing apoptotic pathways, either intrinsic or extrinsic, promotes cancer cell death and arrests the cell cycle. Furthermore, XTL inhibits metastasis, angiogenesis, cancer stemness, drug resistance, cell respiration, etc., which results in tumor aggressiveness inhibition. XTL has low solubility in water, and it has been hypothesized that some modifications, including biotinylation, can improve its pharmacogenetic characteristics. Additionally, XTL derivates such as dihydroXTL and tetrahydroXTL can be helpful for more anti-tumor activities. Using XTL with other anti-tumor agents is another approach to overcome tumor cell resistance. XTL or its derivatives, it is believed, might provide novel chemotherapeutic methods in future cancer therapy.


Assuntos
Antineoplásicos , Humulus , Neoplasias , Propiofenonas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Neoplasias/tratamento farmacológico , Propiofenonas/farmacologia , Propiofenonas/uso terapêutico
15.
Food Chem ; 388: 132964, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35447586

RESUMO

We hypothesised that QuEChERS could be successfully applied to the extraction of bitter acids and xanthohumol from hops, which would be less time consuming, cheaper, and more eco-friendly by the severe reduction of solvent use. High performance liquid chromatography was used to separate the compounds after extraction and quantitation was evaluated against standard calibration curves for bitter acids prepared from an International calibration extract (ICE-4) and an authentic standard of xanthohumol. The standard QuEChERS method was compared to mini and micro-versions including clean-up and spiking procedures. The quantitative analyzes indicate the applicability of the QuEChERS method for the quantitation of bitter acids compared to Soxhlet extraction. The statistical data confirm reproducibility of the total alpha- and beta- acids measured by the standard method and the modified mini- and micro-QuEChERS procedures. Our hypothesis is supported by the data described and is consistent with other previous methods described in the literature.


Assuntos
Humulus , Propiofenonas , Ácidos/análise , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides , Humulus/química , Reprodutibilidade dos Testes
16.
J Pharm Pharmacol ; 74(7): 1017-1026, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35353176

RESUMO

OBJECTIVE: Xanthohumol (XAN), a natural isoflavone from Humulus lupulus L., possesses biological activities on relieving oxidative stress and osteoporosis (OP). This study aimed to evaluate the antioxidative and osteoprotective effect of XAN on Aß-injured osteoblasts, and explore its underlying mechanism. METHODS: Osteoblasts were pretreated with XAN followed by stimulation with Aß1-42. Cell proliferation, ALP activity, bone mineralization and bone formation index were measured. Apoptosis and reactive oxygen species (ROS) were analysed with flow cytometer. PI3K inhibitor LY294002 or siRNA-Nrf2 was added and transfected in osteoblasts, to further confirm whether the pathway participated in the regulation of XAN-induced cytoprotection. KEY FINDINGS: XAN markedly improved the proliferation, differentiation and mineralization of Aß-injured osteoblasts. Additionally, XAN reduced cell apoptosis rate and ROS level, and increased the expression of p-AKT, Nrf2, NQO1, HO-1 and SOD-2. More importantly, LY294002 or siNrf2 abolished the beneficial effect of XAN on osteoblasts activity and decreased the PI3K expression and inhibited its downstream proteins, indicating XAN activated PI3K/AKT/Nrf2 pathway in Aß-injured osteoblasts. CONCLUSION: It was the first time to reveal the antioxidative and osteoprotective effect of XAN through regulating PI3K/AKT/Nrf2 pathway in Aß-injured osteoblasts, which provides reference for the clinical application of XAN in the prevention and treatment of OP.


Assuntos
Fator 2 Relacionado a NF-E2 , Fosfatidilinositol 3-Quinases , Peptídeos beta-Amiloides/metabolismo , Antioxidantes/farmacologia , Apoptose , Flavonoides , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Propiofenonas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Environ Toxicol ; 37(6): 1509-1520, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35229981

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops (Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 µM, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis-related pathways. Xn upregulated the expression of apoptosis-related proteins, namely DR5, cleaved RIP, caspase-3, caspase-8, caspase-9, PARP, Bim, and Bak, and it downregulated the expression of Bcl-2. Xn upregulated the c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn-activated cleaved caspase-3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.


Assuntos
Neoplasias Nasofaríngeas , Inibidores de Poli(ADP-Ribose) Polimerases , Apoptose , Proteínas Reguladoras de Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Flavonoides/farmacologia , Humanos , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Carcinoma Nasofaríngeo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Propiofenonas , Transdução de Sinais
18.
Toxicology ; 470: 153141, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35259468

RESUMO

Deregulation of apoptosis signaling is an important feature of cancer cells and plays an essential role in tumorigenesis. Xanthohumol is an active ingredient in Traditional Chinese Medicines Hops (Humulus lupulus L.). Recently studies have shown the profound anti-tumor activities of Xanthohumol in multiple cancer models. However, its potency in non-small cell lung cancer (NSCLC) and the underlying mechanisms are still elusive. Here, we have investigated the potency of Xanthohumol against NSCLC cells in vitro and xenograft mouse models. Xanthohumol suppressed cell viability, colony formation and induced apoptosis in A549, H520, and H358 cells. Xanthohumol activated mitochondrial apoptosis through upregulation of (p53-upregulated modulator of apoptosis) PUMA expression. After Xanthohumol treatment, the Akt activity was inhibited, which resulted in dephosphorylation of FOXO3a and PUMA induction. Silent PUMA or FOXO3a impaired Xanthohumol-induced apoptosis in NSCLC cells. In nude mice, Xanthohumol administration suppressed NSCLC xenograft tumor growth and increased PUMA expression in tumor tissues. Briefly, our studies revealed a novel mechanism by which Xanthohumol exerted its anti-tumor activity in a PUMA-dependent manner in NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Flavonoides , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Propiofenonas
19.
J Bone Miner Metab ; 40(3): 375-388, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35106609

RESUMO

INTRODUCTION: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. MATERIALS AND METHODS: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3ß (GSK3ß)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. RESULTS: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3ß, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. CONCLUSION: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3ß/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.


Assuntos
Humulus , Sobrecarga de Ferro , Animais , Flavonoides , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/farmacologia , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/farmacologia , Humulus/metabolismo , Ferro/farmacologia , Sobrecarga de Ferro/tratamento farmacológico , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Estresse Oxidativo , Extratos Vegetais/farmacologia , Propiofenonas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
20.
Molecules ; 27(4)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209070

RESUMO

Discovering new and effective drugs for the treatment of Alzheimer's disease (AD) is a major clinical challenge. This study focuses on chemical modulation of the gut microbiome in an established murine AD model. We used the 16S rDNA sequencing technique to investigate the effect of xanthohumol (Xn) on the diversity of intestinal microflora in 2-month- and 6-month-old APP/PS1 mice, respectively. APP/PS1 and wild-type mice were treated by gavage with corn oil with or without Xn every other day for 90 days. Prior to and following treatment, animals were tested for spatial learning, cognitive and memory function. We found Xn reduced cognitive dysfunction in APP/PS1 mice and significantly regulated the composition and abundance of gut microbiota both in prevention experiments (with younger mice) and therapeutic experiments (with older mice). Differential microflora Gammaproteobacteria were significantly enriched in APP/PS1 mice treated with Xn. Nodosilineaceae and Rikenellaceae may be the specific microflora modulated by Xn. The penicillin and cephalosporin biosynthesis pathway and the atrazine degradation pathway may be the principal modulation pathways. Taken together, oral treatment with Xn may have a neuroprotective role by regulating the composition of intestinal microflora, a result that contributes to the scientific basis for a novel prophylactic and therapeutic approach to AD.


Assuntos
Produtos Biológicos/farmacologia , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Propiofenonas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Biodiversidade , Produtos Biológicos/química , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Flavonoides/química , Metagenoma , Metagenômica/métodos , Camundongos , Camundongos Transgênicos , Propiofenonas/química
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