299 research outputs found
Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors
Epithelial-to-mesenchymal transition (EMT) may drive the escape of ALK-rearranged
non-small-cell lung cancer (NSCLC) tumors from ALK-tyrosine kinase inhibitors (TKIs). We investigated
whether first-generation ALK–TKI therapy-induced EMT promotes cross-resistance to
new-generation ALK–TKIs and whether this could be circumvented by the flavonolignan silibinin,
an EMT inhibitor. ALK-rearranged NSCLC cells acquiring a bona fide EMT phenotype upon
chronic exposure to the first-generation ALK–TKI crizotinib exhibited increased resistance to secondgeneration
brigatinib and were fully refractory to third-generation lorlatinib. Such cross-resistance to
new-generation ALK–TKIs, which was partially recapitulated upon chronic TGF stimulation, was
less pronounced in ALK-rearranged NSCLC cells solely acquiring a partial/hybrid E/M transition
state. Silibinin overcame EMT-induced resistance to brigatinib and lorlatinib and restored their
efficacy involving the transforming growth factor-beta (TGF )/SMAD signaling pathway. Silibinin
deactivated TGF -regulated SMAD2/3 phosphorylation and suppressed the transcriptional activation
of genes under the control of SMAD binding elements. Computational modeling studies
and kinase binding assays predicted a targeted inhibitory binding of silibinin to the ATP-binding
pocket of TGF type-1 receptor 1 (TGFBR1) and TGFBR2 but solely at the two-digit micromolar
range. A secretome profiling confirmed the ability of silibinin to normalize the augmented release of TGF into the extracellular fluid of ALK–TKIs-resistant NSCLC cells and reduce constitutive and
inducible SMAD2/3 phosphorylation occurring in the presence of ALK–TKIs. In summary, the ab
initio plasticity along the EMT spectrum may explain the propensity of ALK-rearranged NSCLC cells
to acquire resistance to new-generation ALK–TKIs, a phenomenon that could be abrogated by the
silibinin-driven attenuation of the TGF /SMAD signaling axis in mesenchymal ALK-rearranged
NSCLC cells.Ministry of Science and Innovation, Spain (MICINN)
Spanish GovernmentPlan Nacional de l+D+I PID2019-10455GB-I00
CP20/00003
Spanish GovernmentFundacio Oncolliga Girona (Lliga catalana d'ajuda al malalt de cancer, Girona)Spanish GovernmentCenter for Forestry Research & Experimentation (CIEF)European Commission PI22/00297Grupo Espanol de Cancer de Pulmon (GECP) RTI2019-096724-B-C21La Marato de TV3 foundationHealth Research and Innovation Strategic Plan PROMETEO/2021/059Pla strategic de recerca i innovacio en salut 201906Generalitat de CatalunyaInstituto de Salud Carlos III
SLT006/17/11
Nigella Plants – Traditional Uses, Bioactive Phytoconstituents, Preclinical and Clinical Studies
M. d. M. Contreras thanks the FEDER UJA project 1260905 funded by "Programa Operativo FEDER 2014-2020" and "Consejeria de Economia y Conocimiento de la Junta de Andalucia". This work was also supported by CONICYT PIA/APOYO CCTE AFB170007.Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.Programa Operativo FEDER 2014-2020
1260905Junta de Andalucia
1260905CONICYT PIA/APOYO CCTE
AFB17000
Current Disease-Targets for Oleocanthal as Promising Natural Therapeutic Agent
The broad number of health benefits which can be obtained from the long-term consumption
of olive oil are attributed mainly to its phenolic fraction. Many olive oil phenolics have been studied
deeply since their discovery due to their bioactivity properties, such as Hydroxytyrosol. Similarly,
in the last decade, the special attention of researchers has been addressed to Oleocanthal (OC).
This olive oil phenolic compound has recently emerged as a potential therapeutic agent against
a variety of diseases, including cancer, inflammation, and neurodegenerative and cardiovascular
diseases. Recently, different underlying mechanisms of OC against these diseases have been explored.
This review summarizes the current literature on OC to date, and focuses on its promising bioactivities
against different disease-targets.This work was supported by the project of Spanish Ministry of Science and Innovation
(AGL2015-67995-C3-2-R)
Sweet Cherry Byproducts Processed by Green Extraction Techniques as a Source of Bioactive Compounds with Antiaging Properties
Authors thank GRAFOR BIOTECH S.L. by its support to the project.In the cosmetic industry, there is a continuous demand for new and innovative ingredients
for product development. In the context of continual renovation, both cosmetic companies and
customers are particularly interested in compounds derived from natural sources due to their multiple
benefits. In this study, novel and green-extractive techniques (pressurized solvent, supercritical
CO2, and subcritical water extractions) were used to obtain three new extracts from sweet
cherry stems, a byproduct generated by the food industry. The extracts were characterized by
high-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry
(HPLC-ESI-QTOF-MS), and 57 compounds, mainly flavonoids but also organic and phenolic acids,
fatty acids, and terpenes, were identified. After analytical characterization, a multistep screening
approach, including antioxidant, enzymatic, and photoprotective cellular studies, was used to select
the best extract according to its benefits of interest to the cosmetics industry. The extract obtained
with supercritical CO2 presented the best characteristics, including a wide antioxidant capacity,
especially against lipid peroxyl and •OH free radicals, as well as relevant photoprotective action and
antiaging properties, making it a potential new ingredient for consideration in the development of
new cosmetics.This research was funded by projects RTI2018-096724-B-C21 and 2018-096724-B-C22 from the Spanish
Ministry of Science, Innovation and Universities; APOSTD/2018/097 fellowship from Generalitat Valenciana to
M.H-.L. and CIBER (CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn)
Assessment of conventional and microwave heating effects on the variation of the bioactive compounds of Chétoui VOO using HPLC-DAD-ESI-TOF-MS
The goal of this work was to monitor the hydrophilic profile of the virgin olive oil (VOO)
of the second main Tunisian variety, ‘‘Chétoui”, in order to achieve a better understanding of the
behavior of the bioactive phenolic compounds during 0, 2, 5, 10, and 15 min of microwave heating
at medium power 800 W, and 0, 2.5, and 5 h of conventional heating at 180 ºC. The extent of the
oxidative and hydrolytic degradation of the different phenolic subclasses was evaluated using highperformance
liquid chromatography (HPLC) coupled to electrospray time-of-flight mass spectrometry
(TOF-MS) method. During heating process, the most represented component in Chétoui VOO
was found to be isomer 1 and 2 of deacetoxy oleuropein aglycone, and hydroxy decarboxy oleuropein
aglycon. These compounds may be considered as direct markers for the degree of transformation
of secoiridoids during heating process. Among the studied phenolic compounds,
hydroxytyrosol, tyrosol, luteolin and apigenin displayed the highest heating resistance in the whole
time range of microwave and conventional applications. However, the main secoiridoids quantified
in the fresh VOO, isomer 2 of oleuropein aglycone, and ligstroside aglycone, decreased in concentration
with the thermal treatment and this decrease was drastic under conventional heating.This work was supported by the Ministry of High Education,
and Scientific Research in Tunisia, and the Spanish Ministry of
Economy and Competitiveness (MINECO) (AGL2015-67995-
C3-2-R) and the Andalusian Regional Government Council
(P11-CTS-7625)
Potential Hepatoprotective Activity of Super Critical Carbon Dioxide Olive Leaf Extracts against CCl4-Induced Liver Damage
Virgin olive oil has demonstrated its effective activity against oxidative stress. However,
data on the bioactive effect of olive leaves or their major constituents on the liver are scarce.
The present research work was conducted to evaluate the hepatoprotective effects of supercritical
carbon dioxide (SC-CO2) extracts from fresh and dried olive leaves on hepatotoxicity caused by
carbon tetrachloride (CCl4) in rat models. For this purpose, healthy albino rats of 180–250 g weight
were used. The assessment of biochemical markers was carried out on blood and liver tissue.
Then, a histopathological study was carried out on liver tissue. The obtained results showed that
fresh and dried olive leaf extracts ameliorate the perturbed biochemical parameters caused by CCl4
treatment. Furthermore, the results registered for the histopathological study are in accordance with
the biochemical parameters and the protective capacity of SC-CO2 extracts against DNA damage,
indicating that olive leaf extracts helped to improve liver fibrosis caused by CCl4 treatment.Tunisian Ministry of Higher Education and Scientific Research
LR15CBBC05Spanish Ministry of Economy and Competitiveness (MINECO)
AGL2015-67995-C3-2Junta de Andalucia
B-AGR-466-UGR1
Water Extract of Cryphaea heteromalla (Hedw.) D. Mohr Bryophyte as a Natural Powerful Source of Biologically Active Compounds
Bryophytes comprise of the mosses, liverworts, and hornworts. Cryphaea heteromalla,
(Hedw.) D. Mohr, is a non-vascular lower plant belonging to mosses group. To the date, the most
chemically characterized species belong to the liverworts, while only 3.2% and 8.8% of the species
belonging to the mosses and hornworts, respectively, have been investigated. In this work, we present
Folin–Ciocalteu and oxygen radical absorbance capacity (ORAC) data related to crude extracts of C.
heteromalla obtained by three di erent extraction solvents: pure water (WT), methanol:water (80:20
v/v) (MET), and ethanol:water (80:20 v/v) (ETH). The water extract proved to be the best solvent
showing the highest content of biophenols and the highest ORAC value. The C. heteromalla-WT
extract was investigated by HPLC-TOF/MS (High Performance Liquid Chromatography-Time of
Flight/Mass Spectrometry) allowing for the detection of 14 compounds, five of which were phenolic
compounds, derivatives of benzoic, caffeic, and coumaric acids. Moreover, the C. heteromalla WT
extract showed a protective effect against reactive oxygen species (ROS) generation induced by
tert-butyl hydroperoxide (TBH) on the murine NIH-3T3 fibroblast cell line.This work was supported by the European Social Funding (FSE Sicilia 2020 Project ID: 2014.IT.05.SFOP.014/
3/10.4/9.2.10/0014)
Extraction and Analysis of Phenolic Compounds in Rice: A Review
Rice represents the main source of calorie intake in many world countries and about
60% of the world population include rice in their staple diet. Whole grain rice, also called brown
rice, represent the unpolished version of the more common white rice including bran, germ,
and endosperm. Many health-promoting properties have been associated to the consumption of
whole grain rice and, for this reason, great attention has been paid by the scientific community towards
the identification and the quantification of bioactive compounds in this food item. In this contribution,
the last five years progresses in the quali-quantitative determination of phenolic compounds in
rice have been highlighted. Special attention has been devoted to the most recent strategies for
the extraction of the target compounds from rice along with the analytical approaches adopted
for the separation, identification and quantification of phenolic acids, flavonoids, anthocyanins,
and proanthocyanidins. More specifically, the main features of the “traditional” extraction methods
(i.e., maceration, ultrasound-assisted extraction) have been described, as well as the more innovative
protocols involving advanced extraction techniques, such as MAE (microwave-assisted extraction).
The predominant role of HPLC in the definition of the phenolic profile has been examined also
presenting the most recent results obtained by using mass spectrometry-based detection systems.
In addition, the most common procedures aimed to the quantification of the total amount of the cited
classes of phenolic compounds have been described together with the spectrophotometric protocols
aimed to the evaluation of the antioxidant properties of rice phenolic extracts (i.e., FRAP, DPPH,
ABTS and ORAC)
Optimizing vacuum drying process of polyphenols, flavanols and DPPH radical scavenging assay in pod husk and bean shell cocoa
The objective of this study was to optimize different vacuum drying conditions for cocoa pod husk and cocoa bean shell in order to enhance these by-products for commercial applications. To carry out the optimization, the response surface methodology was applied using a Box–Behnken experimental design with 15 experiments for which different conditions of temperature (X1), drying time (X2) and vacuum pressure (X3) were established. The response variables were the content of total polyphenols, the content of flavanols and the radical scavenging activity evaluated in the extracts of the different experiments. Temperature (50–70 °C), drying time (3–12 h) and vacuum pressure (50–150 mbar) were considered as independent variables. The main factors affecting the response variables were temperature, followed by vacuum pressure. For the content of polyphenols, the optimal response values predicted for the cocoa pod husk was 11.17 mg GAE/g with a confidence limit (95%) of 9.05 to 13.28 mg GAE/g (optimal conditions: 65 °C, 8 h and 75 mbar), while for the cocoa bean shell cocoa was 29.61 mg GAE/g with a confidence limit (95%) of 26.95 to 32.26 mg GAE/g (optimal conditions: 50 °C, 5 h and 100 mbar). Therefore, results of this study suggest a high content of phenolic compounds obtained from these by-products that show relevance as functional ingredients for application in the food, nutraceutical, and cosmeceutical industriesFondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica
of Perú, project number 184-2020-FONDECY
Diet Supplementation with Polyphenol-Rich Salicornia ramosissima Extracts Protects against Tissue Damage in Experimental Models of Cerebral Ischemia
Strokes are the secondmost common cause of death worldwide and a leading cause of disability.
Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event.
For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte
that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental
stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary
supplementation prior to ischemic challenge can prevent subsequent damage using two animal models.
First, we screened the protective effect against hypoxia–reoxygenation in Drosophila melanogaster
and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious
effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract
against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks
of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume
and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical
profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents
a valuable source of bioactive compounds that show promising disease-modifying activities and
could be further developed as an effective food supplement for the prevention or treatment of
neurovascular disorders.PE-0527-2019 Programa Operativo FEDERConsejería de Transformación
Económica, Industria, Conocimiento y Universidades[PY20_01351]ISCIII, grant number [CD21/00148
- …