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This article belongs to the Special Issue Dietary Patterns, Dietary Indices for Colorectal Cancer, Mortality and the Related Disease. ; Cancer mortality rates are undergoing a global downward trend; however, metastasis and relapse after surgery and adjuvant treatments still correlate with poor prognosis and represent the most significant challenges in the treatment of this disease. Advances in genomics, metabolomics, and proteomics are improving our understanding regarding cancer metabolic diversity, resulting in detailed classifications of tumors and raising the effectiveness of precision medicine. Likewise, the growing knowledge of interactions between nutrients and the expression of certain genes could lead to cancer therapies based on precision nutrition strategies. This review aims to identify the recent advances in the knowledge of the mechanistic role of bioactive phytochemicals in foodstuffs in tumor progression, metastasis, and chemo-resistance in order to assess their potential use in precision nutrition therapies targeting relapse in lung, breast, colon, and prostate cancer, and leukemia. A considerable number of bioactive phytochemicals in foodstuffs were identified in the literature with proven effects modulating tumor growth, progression, and metastasis. In addition, the use of foodstuffs in cancer, and specifically in relapse therapies, is being reinforced by the development of different formulations that significantly increase the therapeutic efficiency of these products. This can open the possibility for testing combinations of bioactive phytochemicals with cancer relapse treatments as a potential prevention strategy. ; This research is part of the work plan of Project AGL2016-76736-C3 supported by the Spanish Ministerio de Ciencia, Innovación y Universidades; Project P2018/BAA-4343-ALIBIRD2020-CM supported by the Regional Government of Comunidad de Madrid (V PRICYT). ; Peer reviewed

This is an open access article distributed under the terms of the Creative Commons Attribution License.-- et al. ; Strong evidence suggests that lipid metabolism (LM) has an essential role in tumor growth to support special energetic and structural requirements of tumor cells. Recently, overexpression of LM-related genes, apolipoproteins related to metabolic syndrome, and ACSL/ SCD network involved in fatty acid activation have been proposed as prognostic markers of colon cancer (CC). Furthermore, activation of this latter lipid network has been recently demonstrated to confer invasive and stem cell properties to tumor cells promoting tumor aggressiveness and patient relapse. With the aim of elucidating whether any genetic variation within these genes could influence basal expression levels and consequent susceptibility to relapse, we genotype, in 284 CC patients, 57 polymorphisms located in the 7 genes of these lipid networks previously associated with worse clinical outcome of CC patients (ABCA1, ACSL1, AGPAT1, APOA2, APOC1, APOC2 and SCD), some of them related to CC aggressiveness. After adjusting with clinical confounding factors and multiple comparisons, an association between genotype and disease-free survival (DFS) was shown for rs8086 in 3'-UTR of ACSL1 gene (HR 3.08; 95% CI 1.69-5.63; adjusted p = 0.046). Furthermore, the risk T/T genotype had significantly higher ACSL1 gene expression levels than patients carrying C/T or C/C genotype (means = 5.34; 3.73; 2.37 respectively; p-value (ANOVA) = 0.019), suggesting a functional role of this variant. Thus, we have identified a >risk genotype> of ACSL1 gene that confers constitutive high levels of the enzyme, which is involved in the activation of fatty acids through conversion to acyl-CoA and has been recently related to increased invasiveness of tumor cells. These results suggest that rs8086 of ACSL1 could be a promising prognostic marker in CC patients, reinforcing the relevance of LM in the progression of CC. ; This work was funded by the Ministerio de Economía y Competitividad (Plan Nacional I+D+i AGL2013-48943-C2); Comunidad de Madrid (P2013/ABI-2728. ALIBIRD-CM); and European Union Structural Funds. ; Peer Reviewed

A pressurized water extraction (PWE) method was developed in order to extract β-glucans with bile acids-binding capacities from cultivated mushrooms (Agaricus bisporus, Lentinula edodes, and Pleurotus ostreatus) to be used as supplements to design novel foods with hypocholesterolemic properties. Extraction yields were higher in individual than sequential extractions being the optimal extraction parameters: 200°C, 5 cycles of 5 min each at 10.3 MPa. The crude polysaccharide (PSC) fractions, isolated from the PWE extracts contained mainly β-glucans (including chitooligosaccharides deriving from chitin hydrolysis), α-glucans, and other PSCs (hetero-/proteo-glucans) depending on the extraction temperature and mushroom strain considered. The observed bile acids-binding capacities of some extracts were similar to a β-glucan enriched fraction obtained from cereals. © 2014 American Institute of Chemical Engineers. ; Funded by: European Union within the 7th framework programme. Grant Number: 7FM-PEOPLE-2009-IIF project 251285; Community of Madrid (Spain). Grant Number: ALIBIRD-CM S2009/AGR-1469; Spanish Ministry of Science and Innovation. Grant Number: AGL2010–21537 national R+D and CTICH. ; Peer Reviewed

This is the peer reviewed version of the following article: Palanisamy, M. Testing edible mushrooms to inhibit the pancreatic lipase activity by an in vitro digestion model (2012) International Journal of Food Science and Technology, 47 (5), pp. 1004-1010., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2621.2011.02934.x. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving ; One of the strategies in prevention or treatment of obesity is altering metabolism of lipids by inhibition of dietary fat absorption. The extracts obtained with methanol, water and methanol:water (1:1) from 21 mushroom species were screened as potential sources of pancreatic lipase (PL) inhibitors using a standardised in vitro test. Lepiota procera methanol:water (1:1) extracts showed the highest inhibition activity closely followed by Grifola frondosa, Pleurotus eryngii and Lyophyllum shimeji. Other mushroom strains such as Morchella conica, Marasmius oreades, Lentinula edodes, Amanita ponderosa and Boletus edulis also showed a certain inhibitory activity. However, when the PL inhibitory activity was evaluated using an in vitro digestion model mimicking gut conditions, none of the selected mushroom extracts were able to inhibit PL activity. On the contrary, stimulation of the lipase activity levels was observed and it was not due to endogenous mushroom lipases activities ; The research was supported by the European Union within the 7th framework programme (7FM-PEOPLE-2009-IIF project 251285), ALIBIRD-CM S2009 ⁄AGR-1469 regional program from the Community of Madrid (Spain) and AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovation

The recent development of powerful "omics" technologies (genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has opened new avenues in nutritional sciences toward precision nutrition, which is a genotype-directed nutrition that takes into account the differential responses to nutritional interventions based on gene variation (nutrigenetics) and the effect of nutrients on gene expression (nutrigenomics). Current evidence demonstrates that up to one third of the deaths caused by cancer could be prevented by acting on key risk factors, with diet being one of the most important risk factors due to its association with obesity. Additional factors such as composition of gut microbiome, the immune system, and the nutritional status will have an impact on the final outcome. Nutrient components and bioactive compounds from natural sources can have an impact on cancer progression or even the risk of cancer development by regulating gene expression and/or associated risk factors such as obesity and chronic inflammation. Nowadays, among the different methods to produce natural extracts, the green technology of supercritical fluid extraction (SFE) is quite popular, with a special interest on the use of supercritical CO2 for the extraction of compounds with low polarity. The success of nutritional interventions based on the use of nutraceuticals requires several steps: (i) in vitro and preclinical demonstration of their antitumoral effects; (ii) knowledge of their mechanism of action and molecular targets, which will allow for identification of the specific subgroups of patients who will benefit from them; (iii) the study of genetic variants associated with the differential responses; and (iv) innovative approaches of formulations to improve the in vivo bioavailability of the bioactive ingredients. Herein, we investigate the antitumoral properties and mechanism of action of a supercritical CO2 extract from Calendula officinalis, commonly known as marigold (marigold SFE) in the context of pancreatic cancer. Mechanistically, marigold SFE induces the expression of BMP8B, which leads to an energetic catastrophe ending up with autophagy-induced cell death (AICD). As metabolic reprogramming is a well-recognized hallmark of cancer, the direct impact of marigold SFE on pancreatic cancer cell metabolism encourages further research of its potential as a coadjuvant in pancreatic cancer therapy. Finally, we discuss innovative formulation approaches to augment the clinical therapeutic potential of marigold SFE in nutritional interventions ; This work was supported by the Spanish Ministry of Science (Plan Nacional I + D + i AGL2016-76736-C3), Regional Government of Community of Madrid (P2018/BAA-4343- ALIBIRD2020-CM), Ramón Areces Foundation, and EU Structural Funds

The recent development of powerful "omics" technologies (genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has opened new avenues in nutritional sciences toward precision nutrition, which is a genotype-directed nutrition that takes into account the differential responses to nutritional interventions based on gene variation (nutrigenetics) and the effect of nutrients on gene expression (nutrigenomics). Current evidence demonstrates that up to one third of the deaths caused by cancer could be prevented by acting on key risk factors, with diet being one of the most important risk factors due to its association with obesity. Additional factors such as composition of gut microbiome, the immune system, and the nutritional status will have an impact on the final outcome. Nutrient components and bioactive compounds from natural sources can have an impact on cancer progression or even the risk of cancer development by regulating gene expression and/or associated risk factors such as obesity and chronic inflammation. Nowadays, among the different methods to produce natural extracts, the green technology of supercritical fluid extraction (SFE) is quite popular, with a special interest on the use of supercritical CO2 for the extraction of compounds with low polarity. The success of nutritional interventions based on the use of nutraceuticals requires several steps: (i) in vitro and preclinical demonstration of their antitumoral effects; (ii) knowledge of their mechanism of action and molecular targets, which will allow for identification of the specific subgroups of patients who will benefit from them; (iii) the study of genetic variants associated with the differential responses; and (iv) innovative approaches of formulations to improve the in vivo bioavailability of the bioactive ingredients. Herein, we investigate the antitumoral properties and mechanism of action of a supercritical CO2 extract from Calendula officinalis, commonly known as marigold (marigold SFE) in the context of pancreatic cancer. Mechanistically, marigold SFE induces the expression of BMP8B, which leads to an energetic catastrophe ending up with autophagy-induced cell death (AICD). As metabolic reprogramming is a well-recognized hallmark of cancer, the direct impact of marigold SFE on pancreatic cancer cell metabolism encourages further research of its potential as a coadjuvant in pancreatic cancer therapy. Finally, we discuss innovative formulation approaches to augment the clinical therapeutic potential of marigold SFE in nutritional interventions. ; This work was supported by the Spanish Ministry of Science (Plan Nacional I + D + i AGL2016-76736-C3), Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM), Ramón Areces Foundation, and EU Structural Funds. ; Peer reviewed

This is the peer reviewed version of the following article: Biotechnology Progress 30.2 (2014): 391-400, which has been published in final form at http://dx.doi.org/10.1002/btpr.1865. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving ; A pressurized water extraction (PWE) method was developed in order to extract β-glucans with bile acids-binding capacities from cultivated mushrooms (Agaricus bisporus, Lentinula edodes and Pleurotus ostreatus) to be used as supplements to design novel foods with hypocholesterolemic properties. Extraction yields were higher in individual than sequential extractions being the optimal extraction parameters: 200ºC, 5 cycles of 5 min each at 10.3 MPa. The crude polysaccharide (PSC) fractions, isolated from the PWE extracts contained mainly β-glucans (including chitooligosaccharides deriving from chitin hydrolysis), -glucans and other PSCs (hetero-/proteo-glucans) depending on the extraction temperature and mushroom strain considered. The observed bile acids-binding capacities of some extracts were similar to a β-glucan enriched fraction obtained from cereals. ; The research was supported by the European Union within the 7th framework programme (7FM-PEOPLE-2009-IIF project 251285), ALIBIRD-CM S2009/AGR-1469 regional program from the Community of Madrid (Spain) and AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovation. CTICH is also acknowledged for the cultivation and supplying of the mushrooms fruiting bodies

This is the author's version of a work that was accepted for publication in Journal of Supercritical Fluids .Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Supercritical Fluids 79 (2013): 101-108 http://dx.doi.org/ 10.1016/j.supflu.2012.07.006 ; The use of supercritical fluid technology as an innovative technology to extract bioactive compounds has grown considerably in recent decades. Particularly, the recovery of antioxidants from different herbs is a matter of continuous research and development. Antioxidants can protect cells against the effects of free radicals and thus, play an important role in heart illness, cancer and other diseases. Rosemary (Rosmarinus officinalis L.) has been recognized as one of the Lamiaceae plant with many important biological activities. Particularly, large antioxidant power has been recognized in rosemary and main substances related with this activity were the phenolic diterpenes such as carnosol, rosmanol, carnosic acid, methyl carnosate, and phenolic acids such as the rosmarinic and caffeic acids. Moreover, carnosic acid and carnosol are recognized as the most abundant antioxidants present in rosemary. In this work, supercritical fluid technology was applied to produce rosemary extracts with different compositions and thus, with different bioactivity properties. Selected extracts, from the variety of samples obtained, were used to study the capability of rosemary supercritical extracts to inhibit the proliferation of human liver carcinoma cells. These extracts showed a dose-dependent effect on inhibiting the proliferation of human hepatoma cells. Moreover, observed citostaticity appeared to be significantly influenced by their different composition, suggesting a relevant role of the technology to produce the extracts and the consequently obtained compositions on the potential antitumoral activity of rosemary ; This work has been financed by project AGL2010-21565 (subprogram ALI), RyC 2008- 385 03734, and project INNSAMED IPT-300000-2010-34 (subprogram INNPACTO) from 386 Ministerio de Ciencia e Innovación (Spain), Comunidad Autónoma de Madrid (project 387 ALIBIRD-S2009/AGR-1469) and European Union Structural Funds.

Nowadays, obesity and its associated metabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, or cancer, continue to be a health epidemic in westernized societies, and there is an increased necessity to explore anti-obesity therapies including pharmaceutical and nutraceutical compounds. Considerable attention has been placed on the identification of bioactive compounds from natural sources to manage the metabolic stress associated with obesity. In a previous work, we have demonstrated that a CO2 supercritical fluid extract from yarrow (Yarrow SFE), downregulates the expression of the lipogenic master regulator SREBF1 and its downstream molecular targets FASN and SCD in a tumoral context. Since obesity and diabetes are strongly considered high-risk factors for cancer development, herein, we aimed to investigate the potential therapeutic role of Yarrow SFE in the metabolic stress induced after a high-fat diet in mice. For this purpose, 32 C57BL/6 mice were distributed in four groups according to their diets: standard diet (SD); SD supplemented with Yarrow SFE (SD + Yarrow); high-fat diet (HFD); and HFD supplemented with Yarrow SFE (HFD + Yarrow). Fasting glycemia, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile, gene expression, and lipid content of liver and adipose tissues were analyzed after three months of treatment. Results indicate improved fasting glucose levels in plasma, enhanced insulin sensitivity, and diminished hypercholesterolemia in the HFD + Yarrow group compared to the HFD group. Mechanistically, Yarrow SFE protects liver from steatosis after the HFD challenge by augmenting the adipose tissue buffering capacity of the circulating plasma glucose ; This work was supported by the Spanish Ministry of Science (Plan Nacional I + D + i AGL2016-76736-C3), Regional Government of Community of Madrid (P2013/ABI-2728, ALIBIRD-CM; P2018/BAA-4343-ALIBIRD2020-CM), the Ramón Areces Foundation, and the EU Structural Funds

This article belongs to the Special Issue Dietary Patterns, Dietary Indices for Colorectal Cancer, Mortality and the Related Disease. ; Nowadays, obesity and its associated metabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, or cancer, continue to be a health epidemic in westernized societies, and there is an increased necessity to explore anti-obesity therapies including pharmaceutical and nutraceutical compounds. Considerable attention has been placed on the identification of bioactive compounds from natural sources to manage the metabolic stress associated with obesity. In a previous work, we have demonstrated that a CO2 supercritical fluid extract from yarrow (Yarrow SFE), downregulates the expression of the lipogenic master regulator SREBF1 and its downstream molecular targets FASN and SCD in a tumoral context. Since obesity and diabetes are strongly considered high-risk factors for cancer development, herein, we aimed to investigate the potential therapeutic role of Yarrow SFE in the metabolic stress induced after a high-fat diet in mice. For this purpose, 32 C57BL/6 mice were distributed in four groups according to their diets: standard diet (SD); SD supplemented with Yarrow SFE (SD + Yarrow); high-fat diet (HFD); and HFD supplemented with Yarrow SFE (HFD + Yarrow). Fasting glycemia, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile, gene expression, and lipid content of liver and adipose tissues were analyzed after three months of treatment. Results indicate improved fasting glucose levels in plasma, enhanced insulin sensitivity, and diminished hypercholesterolemia in the HFD + Yarrow group compared to the HFD group. Mechanistically, Yarrow SFE protects liver from steatosis after the HFD challenge by augmenting the adipose tissue buffering capacity of the circulating plasma glucose. ; This work was supported by the Spanish Ministry of Science (Plan Nacional I + D + i AGL2016-76736-C3), Regional Government of Community of Madrid (P2013/ABI-2728, ALIBIRD-CM; P2018/BAA-4343-ALIBIRD2020-CM), the Ramón Areces Foundation, and the EU Structural Funds. ; Peer reviewed

The anticarcinogenic activity of synthetic 1-O-octadecyl-2,3- dibutyroilglycerol (D-SCAKG) in tumor-cell line of colonocytes (SW620) was performed. The effect of the previously digested D-SCAKG under in vitro intestinal conditions was compared to the bioactivity of non-digested D-SCAKG. Antiproliferative activity of each individual product from digestion (1-O-octadecyl-2-butyroilglycerol; 1-O-octadecyl glycerol; butyric acid) was also performed. The impact of solubilization of lipid products within micellar structures was also tested. The 1-O-octadecyl glycerol was the most active compound, followed by 1-O-octadecyl-2-butyroilglycerol, D-SCAKG and butyric acid. The 1-O-octadecyl glycerol and butyric acid were the only molecules that showed antiproliferative effect in absence of micelles. Digested D-SCAKG was 4-fold more effective than non-digested D-SCAKG. A synergism between 1-O-octadecyl-2-butyroilglycerol and 1-O-octadecyl glycerol was evidenced. As summary, the synthetic D-SCAKG seems to be an interesting antitumoral lipid against colonocytes, especially after previous intestinal digestion, and mainly due to the synergism of the major products, namely 1-O-octadecyl-2- butyroilglycerol and 1-O-octadecyl glycerol. At the same time, 1-O-octadecyl-2-butyroilglycerol would constitute a stable esterified form of butyric acid for its vehiculization. © 2013 Published by Elsevier Ireland Ltd. ; This work was supported by Spanish Ministry of Science and Innovation (Plan Nacional I+D+i AGL2010-21565, RyC 2008-03734), Comunidad de Madrid (ALIBIRD, S2009/AGR-1469), European Union Structural Funds and Consolider-Ingenio 2010 Ref. CSD/2007/00063 (FUN-C-FOOD). ; Peer Reviewed

The methanol/water and particularly the water extracts obtained from 26 mushroom species were able to inhibit the 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCR) activity to different extent (10-76%). Cultivated mushrooms such as Pleurotus sp. and Lentinula edodes were among the strains which showed higher HMGCR inhibitory capacities. Their inhibitory properties were not largely influenced by cultivation parameters, mushroom developmental stage or flush number. The HMGCR inhibitory activity of L. edodes was concentrated in the cap excluding the gills while in Pleurotus ostreatus it was distributed through all the different tissues. A method to obtain aqueous fractions with high HMGCR inhibitory activity was optimized using an accelerated solvent extractor (ASE) by selecting 10.7. MPa and 25 °C as common extraction conditions and 5 cycles of 5. min each for P. ostreatus fruiting bodies and 15 cycles of 5. min for L. edodes suggesting that the potential HMGCR inhibitors are different in the two selected mushrooms. © 2012 Elsevier Ltd. ; The research was supported by the European Union within the 7th framework programme (7FM-PEOPLE-2009-IFF project 251285), ALIBIRD-CM S2009/AGR-1469 regional program from the Community of Madrid (Spain),AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovation, and 2010-I-ID-00093 project by ADER (Agency for La Rioja´s economic development). ; Peer Reviewed

The pandemic burden caused by the SARS-CoV-2 coronavirus constitutes a global public health emergency. Increasing understanding about predisposing factors to infection and severity is now a priority. Genetic, metabolic, and environmental factors can play a crucial role in the course and clinical outcome of COVID-19. We aimed to investigate the putative relationship between genetic factors associated to obesity, metabolism and lifestyle, and the presence and severity of SARS-CoV-2 infection. A total of 249 volunteers (178 women and 71 men, with mean and ± SD age of 49 ± 11 years) characterized for dietary, lifestyle habits and anthropometry, were studied for presence and severity of COVID-19 infection, and genotyped for 26 genetic variants related to obesity, lipid profile, inflammation, and biorhythm patterns. A statistically significant association was found concerning a protective effect of APOE rs7412 against SARS-CoV-2 infection (p = 0.039; OR 0.216; CI 0.084, 0.557) after correction for multiple comparisons. This protective effect was also ascribed to the APOɛ2 allele (p = 0.001; OR 0.207; CI 0.0796, 0.538). The genetic variant rs7412 resulting in ApoE2, genetic determinant of lipid and lipoprotein levels, could play a significant role protecting against SARS-CoV-2 infection. ; The authors want to express their gratitude to the GENYAL Platform of Clinical Trials in Nutrition and Health of IMDEA Food Institute for their support, as well as the Counceling of Education of the Community of Madrid for their support in the constitution of GENYAL, and all the volunteers participating in this study. This research was funded by the Plan Nacional I + D + i PID2019 ‐110183RB ‐C21, FACINGLCOVID-CM project. Funding REACT EU Program (Comunidad de Madrid and The European Regional Development Fund. ERDF. European Union). Regional Government of Community of Madrid (Y2020/BIO-6350). Genomic Laboratory GENYALLab (REDLAB, the laboratories network of the Community of Madrid, under the registration number 440). GENYAL LAB ...

This article belongs to the Special Issue Phenolic Compounds in Herbs: Characterization, Antioxidant Properties and Health Benefits. ; 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-1β 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. ; Authors thanks to the Spanish Government (Project: PID2019-110183RB-C22/AEI/10.13039/501100011033) and Comunidad Autónoma de Madrid (ALIBIRD2020-CM (S2018/BAA-4343)) for financial support. ; Peer reviewed

BACKGROUND: Agaricus bisporus mushrooms were able to lower cholesterol levels in hypercholesterolaemic rats and it was suggested that dietary fibre might inhibit cholesterol absorption. However, A. bisporus extracts were also able to inhibit the 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCR, the key enzyme in the cholesterol biosynthetic pathway) and this might also contribute to the observed lowering of cholesterol levels in serum. RESULTS: The methanol-water extracts obtained from A. bisporus were able to inhibit up to 60% the HMGCR activity using an in vitro assay. The HMGCR inhibitory capacities depended on cultivation conditions, strains, etc. The potential inhibitors were not statins, they might be β-glucans able to scavenge the substrate and impair the enzymatic reaction. They were present during all mushroom developmental stages and similarly distributed through all the tissues including the parts discarded as a by-product. Accelerated solvent extractions using 1:1 ethanol-water as pressurised solvent (10.7 MPa, 25°C, five cycles of 5 min) were more effective in the extraction of the HMGCiR inhibitor(s) than supercritical fluid extractions (9 MPa, 40°C) using CO2 with 10% ethanol. CONCLUSION: A mushroom cultivation and two extraction procedures were optimised to obtain fractions from A. bisporus with high HMGCR inhibitory activities to design novel ingredients for hypocholesterolaemic functional foodstuffs ; The research was supported by the European Union within the 7th framework programme (7FM-PEOPLE-2009-IIF Project 251285), by the ALIBIRD-CM S2009/AGR-1469 and ADER 2010-I-ID-0093 regional programs from respectively the Community of Madrid and La Rioja (Spain), and by the AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovation.