Novel bioactive extract from yarrow obtained by the supercritical antisolvent-assisted technique inhibits lipid metabolism in colorectal cancer.

Background: Altered lipid metabolism in cancer is associated to dissemination and prognosis. Bioactive compounds naturally occurring in Achillea millefolium L. (yarrow) have been reported to exert antitumour activities. Food biotechnology may provide on-demand mixtures of bioactive compounds with complementary activities in cancer treatment. Methods: Supercritical-antisolvent-precipitation (SAS) has been applied to fractionate the bioactive compounds from an Ultrasound-Assisted-Extraction yarrow extract resulting in two extracts with distinct polarity, yarrow-precipitate-(PP) and yarrow-separator-(Sep). Total phenolic content and relevant essential oils have been characterized. Antioxidant, anti-inflammatory and antiproliferative activities have been compared. Moreover, the effect on the inhibition of colorectal cancer cells' bioenergetics has been evaluated. Results: Yarrow-PP exerted the highest antioxidant activity, even higher than the complete UAE-yarrow extract, meanwhile yarrow-Sep showed the highest anti-inflammatory activity, even higher than the complete UAE-yarrow extract. Interestingly, yarrow-Sep inhibited key lipid metabolic targets in CRC cells extensively shown to be implicated in cancer dissemination and prognosis -SREBF1, FASN, ABCA1 and HMGCR- and epithelial to mesenchymal targets-CDH1, ATP1B1, CDH2 and Vimentin-augmenting cell adhesion. Conclusions: In summary, SAS technology has been applied to provide a novel combination of bioactive compounds, yarrow-Sep, which merits further research to be proposed as a potential complementary nutraceutical in the treatment of CRC.

Correction: Villalva et al. Antioxidant, Anti-Inflammatory, and Antibacterial Properties of an Achillea millefolium L. Extract and Its Fractions Obtained by Supercritical Anti-Solvent Fractionation against Helicobacter pylori. Antioxidants 2022, 11, 1849.

Table S1 in the Supplementary Material (Phenolic compounds identified in yarrow samples by using HPLC-ESI-QTOF-MS) in the original paper [...].

Combination of Fenugreek and Quinoa Husk as Sources of Steroidal and Triterpenoid Saponins: Bioactivity of Their Co-Extracts and Hydrolysates.

Saponins, both steroidal and triterpenoid, exhibit distinct bioactivities. However, they are not commonly found together in natural sources; instead, sources tend to be rich in one type or another and mainly in the form of saponins rather than the sapogenin aglycones. Developing co-extracts containing both saponin or sapogenin types would be a strategy to harness their respective bioactivities, yielding multibioactive extracts. Therefore, this study evaluates the bioactivity (hypolipidemic, antioxidant, and anti-inflammatory activities) of co-extracts from fenugreek seeds (steroidal-rich saponins) and quinoa husk (triterpenoid-rich saponins), co-extracted at varying proportions, alongside their respective sapogenin-rich hydrolysates. Pancreatic lipase inhibition increased with fenugreek content in co-extracts, especially in sapogenin-rich variants. The latter substantially interfered with cholesterol bioaccessibility (90% vs. 15% in sapogenin-rich extracts). Saponin-rich co-extracts exhibited reduced cytokine release with increased fenugreek content, while sapogenin-rich counterparts showed greater reductions with higher quinoa husk content. Limited cellular antioxidant activities were observed in all extracts, with improved post-hydrolysis bioactivity. Therefore, simultaneous co-extraction of steroidal and triterpenoid sources, such as fenugreek and quinoa husk, as well as their subsequent hydrolysis, are innovative strategies for obtaining multibioactive natural extracts.

Development of Pectin Particles as a Colon-Targeted Marjoram Phenolic Compound Delivery System.

Marjoram is a culinary herb that has been widely employed in folk medicine and presents a high content in phenolics. Thus, the aim of this project was to design formulations to encapsulate phenolic compounds from marjoram to allow their release in the colon. For this purpose, pectin was used as an encapsulating agent, applying two different encapsulation techniques (ionic gelation and spray-drying), followed by a CaCl2 bath. The ionic gelation technique showed a higher yield (77%) compared to spray-drying (31%), and the particles obtained were smaller (267 nm). However, the microparticles obtained by spray-drying presented a higher encapsulation efficiency (93%). Moreover, spray-dried microparticles protected a higher percentage of the encapsulated phenolics from the action of gastrointestinal pHs and enzymes. Hence, the results showed that spray-drying was a more appropriate technique than ionic gelation for the encapsulation of marjoram phenolics in order to protect them during the gastrointestinal step, facilitating their arrival in the colon. These microparticles would also be suitable for inclusion in food matrices for the development of phenolic colon delivery systems.

Polyphenols as NLRP3 inflammasome modulators in cardiometabolic diseases: a review of in vivo studies.

The nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs) are components of the innate immune system, important in coordinating the inflammatory response. Among them, NLRP3 can form inflammasomes, multiprotein complexes activating the inflammatory caspase-1 and leading, through a cell death-mediated signaling cascade, to the release of several proinflammatory cytokines. Dietary polyphenols, plant secondary metabolites, have been reported to exhibit anti-inflammatory properties, although studies have focused most on their effect on the expression of the final circulating cytokines rather than on the upstream signals activating the NLRP3 inflammasome. The present review explores current knowledge on the potential of dietary polyphenols to regulate the whole NLRP3 inflammasome pathway, in the context of cardiometabolic pathologies (obesity, cardiovascular diseases, type 2 diabetes and non-alcoholic fatty liver disease), based on in vivo studies. A clear tendency towards a decrease in the expression of the whole NLRP3 inflammasome signaling pathway when several animal models were supplemented with polyphenols was observed, commonly showing a dose-response effect; these modifications were concomitant with clinical improvements in the pathologies. Nevertheless, the diversity of doses used, the disparity in polyphenol structures tested and, particularly, the scarce clinical trials and exploration of mechanisms of action show the need to develop further research on the topic.

Reply to Franski, R.; Beszterda-Buszczak, M. Comment on "Villalva et al. Antioxidant, Anti-Inflammatory, and Antibacterial Properties of an Achillea millefolium L. Extract and Its Fractions Obtained by Supercritical Anti-Solvent Fractionation against Helicobacter pylori. Antioxidants 2022, 11, 1849".

Franski and Beszterda-Buszczak [...].

Biological Activities of Miracle Berry Supercritical Extracts as Metabolic Regulators in Chronic Diseases.

Synsepalum dulcificum (Richardella dulcifica) is a berry fruit from West Africa with the ability to convert the sour taste into a sweet taste, and for this reason, the fruit is also known as the "miracle berry" (MB). The red and bright berry is rich in terpenoids. The fruit's pulp and skin contain mainly phenolic compounds and flavonoids, which correlate with their antioxidant activity. Different polar extracts have been described to inhibit cell proliferation and transformation of cancer cell lines in vitro. In addition, MB has been shown to ameliorate insulin resistance in a preclinical model of diabetes induced by a chow diet enriched in fructose. Herein, we have compared the biological activities of three supercritical extracts obtained from the seed-a subproduct of the fruit-and one supercritical extract obtained from the pulp and the skin of MB. The four extracts have been characterized in terms of total polyphenols content. Moreover, the antioxidant, anti-inflammatory, hypo-lipidemic, and inhibition of colorectal cancer cell bioenergetics have been compared. Non-polar supercritical extracts from the seed are the ones with the highest effects on the inhibition of bioenergetic of colorectal (CRC) cancer cells. At the molecular level, the effects on cell bioenergetics seems to be related to the inhibition of main drivers of the de novo lipogenesis, such as the sterol regulatory element binding transcription factor (SREBF1) and downstream molecular targets fatty acid synthase (FASN) and stearoyl coenzyme desaturase 1 (SCD1). As metabolic reprograming is considered as one of the hallmarks of cancer, natural extracts from plants may provide complementary approaches in the treatment of cancer. Herein, for the first time, supercritical extracts from MB have been obtained, where the seed, a by-product of the fruit, seems to be rich in antitumor bioactive compounds. Based on these results, supercritical extracts from the seed merit further research to be proposed as co-adjuvants in the treatment of cancer.

Implication of the Polymeric Phenolic Fraction and Matrix Effect on the Antioxidant Activity, Bioaccessibility, and Bioavailability of Grape Stem Extracts.

The bioaccessibility and bioavailability of phenolics compounds of two grape stem extracts with different composition were studied. High polymeric extract (HPE) presented a higher content of total phenolics (TPC), procyanidins, hemicelluloses, proteins, and ashes, whereas low procyanidin extract (LPE) showed a higher fat, soluble sugars, and individual phenolic compounds content. Corresponding to its higher total phenolics content, HPE possesses a higher antioxidant activity (TEAC value). The digestion process reduced the antioxidant activity of the HPE up to 69%, due to the decrease of TPC (75%) with a significant loss of polymeric compounds. LPE antioxidant activity was stable, and TPC decreased by only 13% during the digestion process. Moreover, a higher antioxidant phenolic compounds bioavailability was shown in LPE in contrast to HPE. This behaviour was ascribed mainly to the negative interaction of polymeric fractions and the positive interaction of lipids with phenolic compounds. Therefore, this study highlights the convenience of carrying out previous studies to identify the better extraction conditions of individual bioavailable phenolic compounds with antioxidant activity, along with those constituents that could increase their bioaccessibility and bioavailability, such as lipids, although the role played by other components, such as hemicelluloses, cannot be ruled out.

Participatory action research intervention for improving sleep in inpatients with cancer.

AIM: To design and implement a plan to improve oncohaematological patients' sleep. BACKGROUND: The hospital environment can compromise inpatients' sleep, negatively impacting on health outcomes and patient satisfaction. DESIGN AND METHOD: The improvement plan was designed in collaboration with 18 professionals, 3 patients and 3 accompanying relatives. The study designed followed the SQUIRE 2.0 guidelines. Outcome variables were self-reported patient satisfaction regarding sleep, measured using a 30-item, ad hoc questionnaire and a 10-point visual analogue scale, completed by 318 oncohaematological inpatients (pre-intervention n = 120, post-intervention, n = 198) in a comprehensive cancer centre in Spain from 2017 to 2019. RESULTS: Overall, 61.5% (n = 190) of the inpatients reported sleep alterations, and 92.6% reported interruptions in their nightly sleep. Half slept less than 6 h/night, but 58.0% said they felt rested upon waking, despite the interruptions. These outcomes were similar before and after the intervention. The improvement plan identified four domains for work (professionals, care procedures, instruments/environment and patients/relatives), 10 areas for improvement and 35 actions for implementation. However, overall sleep worsened significantly, from 6.73 to 6.06 on the 10-point scale. The intervention significantly improved variables related to professionals' behaviour, including noise during the shift change, conversations at the control desk and the use of corridor lights. Sleep disturbances were mainly caused by pain/discomfort and infuser alarms, and collectively they decreased significantly after the intervention (p = .008). However, overall sleep worsened significantly, from 6.73 to 6.06 on the 10-point scale. CONCLUSIONS: Pain, clinical devices and noise made by professionals are the main causes of sleep disturbances. Involving professionals in decision-making to improve patients' sleep have a positive impact on noise levels. RELEVANCE TO CLINICAL PRACTICE: This study proposes new strategies for improving sleep by increasing staff awareness and changing attitudes towards patients' sleep. Nurses should be involved in addressing sleep disturbances during hospitalization.

Bioavailability Assessment of Yarrow Phenolic Compounds Using an In Vitro Digestion/Caco-2 Cell Model: Anti-Inflammatory Activity of Basolateral Fraction.

In this study, a combined in vitro digestion/Caco-2 model was performed with the aim to determine the phenolic compounds bioavailability of two yarrow extracts. HPLC-PAD characterisation indicated that the main components in both extracts were 3,5-dicaffeoylquinic acid (DCQA) and luteolin-7-O-glucoside. Analyses after the simulated digestion process revealed that phenolic composition was not affected during the oral phase, whereas gastric and intestinal phases represented critical steps for some individual phenolics, especially intestinal step. The transition from gastric medium to intestinal environment caused an important degradation of 3,5-DCQA (63-67% loss), whereas 3,4-DCQA and 4,5-DCQA increased significantly, suggesting an isomeric transformation within these caffeic acid derivatives. However, an approx. 90% of luteolin-7-O-glucoside was recovered after intestinal step. At the end of Caco-2 absorption experiments, casticin, diosmetin and centaureidin represented the most abundant compounds in the basolateral fraction. Moreover, this fraction presented anti-inflammatory activity since was able to inhibit the secretion of IL-1ß and IL-6 pro-inflammatory cytokines. Thus, the presence in the basolateral fraction of flavonoid-aglycones from yarrow, could be related with the observed anti-inflammatory activity from yarrow extract.

Encapsulation of Marjoram Phenolic Compounds Using Chitosan to Improve Its Colon Delivery.

In this study, chitosan particles were used to encapsulate marjoram phenolic compounds as colon-specific drug-delivery systems. The microparticles were prepared by ionic gelation and spray-drying techniques and varying amounts of polymer and extract, along with different method conditions. The spray drying of microparticles (0.75% low molecular weight chitosan dissolved in 0.4% of acetic acid) presented the best encapsulation efficiency (near 75%), with size ranges from 1.55 to 1.68 µm that allowed the encapsulation of 1.25-1.88 mg/mL of extract. Release studies of individual marjoram phenolic compounds at pH 2 and 7.4 showed that most of the compounds remained encapsulated in the microparticles. Only arbutin and vicenin II presented a high initial burst release. As the polarity of the compounds was reduced, their initial release decreased. In addition, after gastrointestinal digestion, most of marjoram phenolic compounds remained encapsulated. These results prove that chitosan microparticlescould protect the marjoram phenolic compounds during gastrointestinal digestion, specifically those related to anticancer activity, which enables their application as colon-specific delivery systems.

Antioxidant, Anti-Inflammatory, and Antibacterial Properties of an Achillea millefolium L. Extract and Its Fractions Obtained by Supercritical Anti-Solvent Fractionation against Helicobacter pylori.

The main objective of this work is to evaluate the potential utility of an Achillea millefolium extract (yarrow extract, YE) in the control of H. pylori infection. The supercritical anti-solvent fractionation (SAF) process of YE allowed the obtaining of two different fractions: yarrow's precipitated fraction (YPF), enriched in most polar phenolic compounds (luteolin-7-O-glucoside, luteolin, and 3,5-dicaffeoylquinic acid), and yarrow's separator fraction (YSF), enriched in monoterpenes and sesquiterpenes, mainly containing camphor, artemisia ketone, and borneol. YE was effective in reducing reactive oxygen species (ROS) production in human gastric AGS cells by 16% to 29%, depending on the H. pylori strain. YPF had the highest inhibitory activity (38-40%) for ROS production. YE modulated the inflammatory response in AGS gastric cells, decreasing IL-8 production by 53% to 64%. This IL-8 inhibition also showed a strain-dependent character. YPF and YSF exhibited similar behavior, reducing IL-8 production, suggesting that both phenolic compounds and essential oils could contribute to IL-8 inhibition. YSF showed the highest antibacterial activity against H. pylori (6.3-7.1 log CFU reduction, depending on the strain) and lower MIC (0.08 mg/mL). Results obtained have shown that YE and SAF fractions (YPF and YSF) were effective as antioxidant, anti-inflammatory, and antibacterial agents regardless of the H. pylori strain characteristics.

Sustainable Extraction Techniques for Obtaining Antioxidant and Anti-Inflammatory Compounds from the Lamiaceae and Asteraceae Species.

Melissa officinalis L. and Origanum majorana L., within Lamiaceae family, and Calendula officinalis L. and Achillea millefolium L., within the Asteraceae, have been considered a good source of bioactive ingredients with health benefits. In this study, the supercritical fluid extraction (SFE) using pure CO2, and the ultrasound assisted extraction (UAE) were proposed as green techniques to obtain plant-based extracts with potential antioxidant and anti-inflammatory activities. Higher values of total phenolic content and antioxidant activity were achieved in UAE ethanol:water (50:50, v/v) extracts. Meanwhile, UAE pure ethanol extracts showed greater anti-inflammatory activity. RP-HPLC-PAD-ESI-QTOF-MS/MS analysis showed a vast number of phenolic compounds in the extracts, including unreported ones. O. majorana ethanol:water extract presented the highest content of phenolics and antioxidant activity; among its composition, both rosmarinic acid and luteolin glucoside derivatives were abundant. The pure ethanol extract of A. millefolium resulted in an important content of caffeoylquinic acid derivatives, luteolin-7-O-glucoside and flavonoid aglycones, which could be related to the remarkable inhibition of TNF-α, IL-1ß and IL-6 cytokines. Besides, borneol and camphor, found in the volatile fraction of A. millefolium, could contributed to this latter activity. Thus, this study points out that O. majorana and A. millefolium are considered a promising source of bioactive ingredients with potential use in health promotion.

The Health Benefits of the Bioactive Compounds in Foods.

The health benefits of consuming certain foods have been commonly known since ancient times [...].

Valorisation of Grape Stems as a Source of Phenolic Antioxidants by Using a Sustainable Extraction Methodology.

Pressurized liquid extraction with ethanol:water mixtures was proposed for obtaining phenolic antioxidants from grape stems. The optimal extraction conditions were elucidated by using a central composite rotatable design (solvent (X1, 0-100% ethanol:water v/v), temperature (X2, 40-120 °C) and time (X3, 1-11 min)). Response surface methodology determined 30% ethanol:water, 120 °C and 10 min as the optimal extraction conditions regarding total phenolic content (TPC) (185.3 ± 2.9 mg gallic acid/g of extract) and antioxidant activity (3.55 ± 0.21 mmol Trolox/g, 1.22 ± 0.06 mmol Trolox/g and 1.48 ± 0.17 mmol Trolox/g of extract in ABTS, DPPH and ORAC methodologies, respectively). The antioxidant activity was attributed to total polymer procyanidins and flavan-3-ol monomers and oligomers, although other phenolic compound contributions should not be ruled out. Forty-two phenolic compounds were identified in the optimal extract, mainly polymer procyanidins and, to a lesser extent, monomers and oligomers of flavan-3-ols, quercetin-3-O-glucuronide, ε-viniferin, gallic and caftaric acid. Ethyl gallate, ellagic acid, protocatechuic aldehyde, delphinidin-7-O-glucoside and cyanidin-3-O-glucoside were reported for the first time in grape stem extracts. In conclusion, this study highlights the use of this winery side stream as a source of antioxidants within a sustainable food system.

Protein matrices ensure safe and functional delivery of rosmarinic acid from marjoram (Origanum majorana) extracts.

BACKGROUND: To understand the interactions between carriers and functional ingredients is crucial when designing delivery systems, to maximize bioefficacy and functionality. In this study, two different protein matrices were evaluated as means to protect the extract isolated from marjoram leaves (Origanum majorana), casein micelles from fresh skim milk and soy protein isolate (SPI). RESULTS: Marjoram extract was obtained from pressurization of ethanol and water solvent. Protein dispersions of casein and SPI (5 g L-1 each) with or without marjoram extract (0.1-3 mg mL-1 ) were prepared and homogenized. The physicochemical characterization of charge and entrapment efficiency were conducted. The results demonstrated that entrapment efficiency was highly dependent on the carrier itself where SPI formulations showed 20% higher affinity when compared to casein micelles. To investigate the physiological behaviour of the marjoram-protein dispersions, human macrophages were employed. A non-specific inflammatory response of macrophages stimulated with bacterial lipopolysaccharide was measured for TNF-α, IL-1ß and IL-6 cytokine secretion. CONCLUSION: Casein and SPI protein formulations warranted high bioefficacy of marjoram extract, showing their potential as safe carriers. © 2018 Society of Chemical Industry.

Anti-Inflammatory and Antioxidant Activities from the Basolateral Fraction of Caco-2 Cells Exposed to a Rosmarinic Acid Enriched Extract.

The potential use of Origanum majorana L. as a source of bioavailable phenolic compounds, specifically rosmarinic acid (RA), has been evaluated. Phenolic bioavailability was tested using an in vitro digestion process followed by a Caco-2 cellular model of intestinal absorption. The high-performance liquid chromatography-photodiode array detector-tandem mass spectrometry (HPLC-PAD-MS/MS) analysis showed the main components in the extract were 6-hydroxyluteolin-7-O-glucoside and rosmarinic acid, followed by luteolin-O-glucoside. After digestion process, the amount of total phenolic compounds (TPC) only decreased slightly, although a remarkable reduction in RA (near 50%) was detected. Bioavailable fraction contained 7.37 ± 1.39 mg/L digested extract of RA with small quantities of lithospermic acid and diosmin and presented an important antioxidant activity (0.89 ± 0.09 mmol Trolox/L digested extract). Besides, this bioavailable fraction produced a significant inhibition in TNF-α, IL-1ß, and IL-6 secretion, using a human THP-1 macrophages model. Therefore, RA content in the basolateral compartment could play an important role in the antioxidant and anti-inflammatory activities found.

Vaccinium meridionale Swartz extracts and their addition in beef burgers as antioxidant ingredient.

BACKGROUND: Vaccinium meridionale Swartz (mortiño) constitutes a source of bioactive phytochemicals, but reports related to its efficient and green production are scarce. In this study, pressurized liquid extraction (PLE) and ultrasound-assisted extraction of mortiño were compared. Total phenolic content (TPC) and antioxidant capacity (ABTS•+ ) were determined. Beef burgers with 20 g kg-1 of mortiño (MM) or its PLE extract (ME) were manufactured. Lipid oxidation (TBARS) and instrumental color changes were measured after refrigerated storage. RESULTS: High TPC (up to 72 g gallic acid equivalent kg-1 extract) was determined in mortiño extracts, which was positively correlated with antioxidant activity. TBARS values of beef burgers containing either MM or ME did not change after refrigerated storage, whereas lipid oxidation of control burgers increased significantly. The color of burgers with added MM or ME was different (lower b* and a* values) from that of control burgers. However, the evolution of color after storage was similar between control and ME samples. CONCLUSION: Mortiño extracts with high TPC can be obtained by PLE. Both mortiño and its PLE extract are able to control lipid oxidation of beef burgers, but the extract is preferred from the color quality point of view. © 2017 Society of Chemical Industry.

Biological Activities of Asteraceae (Achillea millefolium and Calendula officinalis) and Lamiaceae (Melissa officinalis and Origanum majorana) Plant Extracts.

Asteraceae (Achillea millefolium and Calendula officinalis) and Lamiaceae (Melissa officinalis and Origanum majorana) extracts were obtained by applying two sequential extraction processes: supercritical fluid extraction with carbon dioxide, followed by ultrasonic assisted extraction using green solvents (ethanol and ethanol:water 50:50). The extracts were analyzed in terms of the total content of phenolic compounds and the content of flavonoids; the volatile oil composition of supercritical extracts was analyzed by gas chromatography and the antioxidant capacity and cell toxicity was determined. Lamiaceae plant extracts presented higher content of phenolics (and flavonoids) than Asteraceae extracts. Regardless of the species studied, the supercritical extracts presented the lowest antioxidant activity and the ethanol:water extracts offered the largest, following the order Origanum majorana > Melissa officinalis ≈ Achillea millefolium > Calendula officinalis. However, concerning the effect on cell toxicity, Asteraceae (especially Achillea millefolium) supercritical extracts were significantly more efficient despite being the less active as an antioxidant agent. These results indicate that the effect on cell viability is not related to the antioxidant activity of the extracts.

Extraction of functional ingredients from spinach (Spinacia oleracea L.) using liquid solvent and supercritical CO2 extraction.

BACKGROUND: In this work three different techniques were applied to extract dry leaves of spinach (Spinacia oleracea): solid-liquid extraction (SLE), pressurised liquid extraction (PLE) and supercritical fluid extraction (SFE) to investigate the influence of extraction solvent and technique on extracts composition and antioxidant activity. Moreover, the influence of carotenoids and phenolic compounds on the antioxidant and anti-inflammatory activities of spinach extracts was also studied. RESULTS: The higher concentrations of carotenoids and the lower content of phenolic compounds were observed in the supercritical CO2 extracts; whereas water and/or ethanol PLE extracts presented low amounts of carotenoids and the higher concentrations of phenolic compounds. PLE extract with the highest content of phenolic compounds showed the highest antioxidant activity, although SFE carotenoid rich extract also showed a high antioxidant activity. Moreover, both extracts presented an important anti-inflammatory activity. CONCLUSION: PLE seems to be a good technique for the extraction of antioxidant and anti-inflammatory compounds from spinach leaves. Moreover, spinach phenolic compounds and carotenoids present a high antioxidant activity, whereas spinach carotenoids seem to show a higher anti-inflammatory activity than phenolic compounds. It is worth noting that of our knowledge this is the first time the anti-inflammatory activity of lipophilic extracts from spinach leaves is reported.