{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:07:45Z","timestamp":1789474065324,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Dysregulated hepatic cholesterol handling and oxidative stress represent key targets for nutritional interventions. This study investigated a combination of Ophiocordyceps sinensis (formerly Cordyceps sinensis) extract and coenzyme Q10 (CoQ10) using a sequential gut\u2013liver in vitro model. Differentiated Caco-2\/HT29-MTX co-cultures were used to assess intestinal transport, transepithelial electrical resistance (TEER), and junctional organisation. The resulting basolateral intestinal-conditioned medium was applied to high-glucose-stressed HepG2 cells. The combined treatment-maintained epithelial electrical integrity (TEER &gt; 400 \u03a9\u00b7cm2) and tight junction protein abundance, while transiently increasing paracellular fluorescein transport (Papp) and enhancing basolateral CoQ10 recovery (+29%). In HepG2 cells, the conditioned medium reduced superoxide production (\u221238%) and enhanced both DiI-labelled low-density lipoprotein (DiI-LDL) uptake (+26%) and intracellular total bile acid content (+33%). These functional outcomes were accompanied by coordinated changes in protein abundance: a decrease in sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and proprotein convertase subtilisin\/kexin type 9 (PCSK9) levels, alongside increased low-density lipoprotein receptor (LDLR), cytochrome P450 family 7 subfamily A member 1 (CYP7A1), and ATP-binding cassette transporter A1 (ABCA1) expression. Pharmacological inhibition with dorsomorphin suggested a partial involvement of AMP-activated protein kinase (AMPK) signalling, although this mechanistic assessment remained exploratory. Overall, these findings demonstrate the coordinated modulation of intestinal transport, functional hepatic endpoints, and cholesterol-related protein abundance.<\/jats:p>","DOI":"10.3390\/molecules31183265","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:57:34Z","timestamp":1789473454000},"page":"3265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Hepatic Cholesterol-Related Pathways by Ophiocordyceps sinensis and Coenzyme Q10 in a Sequential Gut\u2013Liver In Vitro Model"],"prefix":"10.3390","volume":"31","author":[{"given":"Simone","family":"Mul\u00e8","sequence":"first","affiliation":[{"name":"Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, Piazza Sant\u2019Eusebio 5, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Galla","sequence":"additional","affiliation":[{"name":"Noivita s.r.l.s., Spin Off of University of Piemonte Orientale, Strada Privata Curti n. 7, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Musu","sequence":"additional","affiliation":[{"name":"Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, Piazza Sant\u2019Eusebio 5, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Parini","sequence":"additional","affiliation":[{"name":"Noivita s.r.l.s., Spin Off of University of Piemonte Orientale, Strada Privata Curti n. 7, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Molinari","sequence":"additional","affiliation":[{"name":"Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, Piazza Sant\u2019Eusebio 5, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-270X","authenticated-orcid":false,"given":"Francesca","family":"Uberti","sequence":"additional","affiliation":[{"name":"Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, Piazza Sant\u2019Eusebio 5, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrcardio.2011.2","article-title":"Pharmacological strategies for lowering LDL cholesterol: Statins and beyond","volume":"8","author":"Brautbar","year":"2011","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Luo, F., Yu, L., Xian, X., Shan, B., and Das, A. (2024). Editorial: New and emerging lipid-lowering therapies for reducing cardiovascular risk: Beyond statins. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1364170"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jcsm.12654","article-title":"Effects of statins on mitochondrial pathways","volume":"12","author":"Mollazadeh","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40256-017-0251-2","article-title":"Does coenzyme Q10 supplementation mitigate statin-associated muscle symptoms? Pharmacological and methodological considerations","volume":"18","author":"Taylor","year":"2018","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1210\/jc.2018-01185","article-title":"Statin treatment decreases mitochondrial respiration but muscle coenzyme Q10 levels are unaltered: The LIFESTAT study","volume":"104","author":"Dohlmann","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1194\/jlr.M008144","article-title":"High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol","volume":"51","author":"Welder","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_7","unstructured":"Pokhrel, B., Pellegrini, M.V., and Levine, S.N. (2025). PCSK9 inhibitors. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_8","first-page":"503","article-title":"Increasing the value of rice by transformation into red yeast rice","volume":"34","author":"Pratoomchai","year":"2015","journal-title":"J. Sci. Technol. Mahasarakham Univ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.atherosclerosissup.2019.08.023","article-title":"The role of red yeast rice (RYR) supplementation in plasma cholesterol control: A review and expert opinion","volume":"39","author":"Banach","year":"2019","journal-title":"Atheroscler. Suppl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s40264-018-0661-3","article-title":"Adverse events to food supplements containing red yeast rice: Comparative analysis of FAERS and CAERS reporting systems","volume":"41","author":"Raschi","year":"2018","journal-title":"Drug Saf."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Norata, G.D., and Banach, M. (2024). The impact of red yeast rice extract use on the occurrence of muscle symptoms and liver dysfunction: An update from the adverse event reporting systems and available meta-analyses. Nutrients, 16.","DOI":"10.3390\/nu16030444"},{"key":"ref_12","first-page":"69","article-title":"Nutraceutical alternatives to red yeast rice extract\/monacolin K for moderate hypercholesterolaemia: Current evidence and knowledge gaps","volume":"1","author":"Comi","year":"2022","journal-title":"Eur. Atheroscler. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/012772574X285280240220065812","article-title":"Cholesterol absorption inhibition by some nutraceuticals","volume":"16","author":"Kumar","year":"2025","journal-title":"Recent Adv. Food Nutr. Agric."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/clc.22862","article-title":"Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience","volume":"41","author":"Ward","year":"2018","journal-title":"Clin. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"312","DOI":"10.2174\/0127724328250471231222094648","article-title":"Berberine: A multi-target natural PCSK9 inhibitor with the potential to treat diabetes, Alzheimer\u2019s disease, cancer, and cardiovascular disease","volume":"19","author":"Coppinger","year":"2024","journal-title":"Curr. Rev. Clin. Exp. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"mjad073","DOI":"10.1093\/jmcb\/mjad073","article-title":"The interplay between the muscle and liver in the regulation of glucolipid metabolism","volume":"15","author":"Chen","year":"2024","journal-title":"J. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1617805","DOI":"10.1155\/2020\/1617805","article-title":"Role of oxidative stress in hepatic and extrahepatic dysfunctions during nonalcoholic fatty liver disease (NAFLD)","volume":"2020","author":"Gonzalez","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0711","DOI":"10.1097\/HC9.0000000000000711","article-title":"Skeletal muscle and MASLD: Mechanistic and clinical insights","volume":"9","author":"Marjot","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1172\/JCI29383","article-title":"Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice","volume":"116","author":"Lagace","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hwang, J.T., Choi, E., Choi, H.K., Park, J.H., and Chung, M.Y. (2021). The cholesterol-lowering effect of Capsella bursa-pastoris is mediated via SREBP2- and HNF-1\u03b1-regulated PCSK9 inhibition in obese mice and HepG2 cells. Foods, 10.","DOI":"10.3390\/foods10020408"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhong, S., Li, J., Wei, M., Deng, Z., and Liu, X. (2023). Fresh and browned lotus root extracts promote cholesterol metabolism in FFA-induced HepG2 cells through different pathways. Foods, 12.","DOI":"10.3390\/foods12091781"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/aps.2016.134","article-title":"Lowering serum lipids via PCSK9-targeting drugs: Current advances and future perspectives","volume":"38","author":"He","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1096\/fj.201700442R","article-title":"AMPK in skeletal muscle function and metabolism","volume":"32","author":"Hingst","year":"2018","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12944-017-0541-3","article-title":"Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: A review","volume":"16","author":"Oscarsson","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, X., Xin, Y., Mo, Y., Marozik, P., He, T., and Guo, H. (2022). The bioavailability and biological activities of phytosterols as modulators of cholesterol metabolism. Molecules, 27.","DOI":"10.3390\/molecules27020523"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/fob2.70018","article-title":"Bioactive polysaccharides and their potential health benefits in reducing the risks of metabolic syndrome: A review","volume":"2","author":"Oyalo","year":"2025","journal-title":"Food Biomacromol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mul\u00e8, S., Galla, R., Parini, F., Botta, M., Ferrari, S., and Uberti, F. (2025). An in vitro gut-liver-adipose axis model to evaluate the anti-obesity potential of a novel probiotic-polycosanol combination. Foods, 14.","DOI":"10.3390\/foods14112003"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.lwt.2015.03.109","article-title":"A comparison of chemical composition, bioactive components and antioxidant activity of natural and cultured Cordyceps sinensis","volume":"63","author":"Wang","year":"2015","journal-title":"LWT Food Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jff.2013.04.018","article-title":"Bioactive principles from Cordyceps sinensis: A potent food supplement\u2014A review","volume":"5","author":"Shashidhar","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.numecd.2013.09.019","article-title":"\u03b2-Glucan attenuates inflammatory responses in oxidized LDL-induced THP-1 cells via the p38 MAPK pathway","volume":"24","author":"Wang","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ashraf, S.A., Elkhalifa, A.E.O., Siddiqui, A.J., Patel, M., Awadelkareem, A.M., Snoussi, M., Ashraf, M.S., Adnan, M., and Hadi, S. (2020). Cordycepin for health and wellbeing: A potent bioactive metabolite of an entomopathogenic fungus. Molecules, 25.","DOI":"10.3390\/molecules25122735"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1177\/1096620X251380195","article-title":"Wild Cordyceps polysaccharides alleviate atherosclerosis by attenuating macrophage cholesterol accumulation through the PPAR\u03b3-LXR\u03b1-ABCA1\/ABCG1 pathway","volume":"28","author":"Liu","year":"2025","journal-title":"J. Med. Food"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.jff.2012.02.009","article-title":"Comparison of the hepatoprotective activity between cultured Cordyceps militaris and natural Cordyceps sinensis","volume":"4","author":"Wang","year":"2012","journal-title":"J. Funct. Foods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jff.2017.12.045","article-title":"Oat \u03b2-glucan inhibits adipogenesis and hepatic steatosis in high-fat diet-induced hyperlipidemic mice via AMPK signaling","volume":"41","author":"Liu","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/jcmm.12187","article-title":"Cordycepin activates AMP-activated protein kinase (AMPK) via interaction with the \u03b31 subunit","volume":"18","author":"Wu","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115163","DOI":"10.1016\/j.biopha.2023.115163","article-title":"Cordycepin inhibits myogenesis via activating the ERK1\/2 MAPK signalling pathway in C2C12 cells","volume":"165","author":"Cheng","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Xie, T., Wang, C., Jin, Y., Meng, Q., Liu, Q., Wu, J., and Sun, H. (2020). Coenzyme Q10-induced activation of the AMPK-YAP-OPA1 pathway alleviates atherosclerosis by improving mitochondrial function, inhibiting oxidative stress and promoting energy metabolism. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01034"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13388","DOI":"10.3390\/ijms150813388","article-title":"Water-soluble coenzyme Q10 inhibits nuclear translocation of apoptosis-inducing factor and cell death caused by mitochondrial complex I inhibition","volume":"15","author":"Li","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Van Laar, A., Grootaert, C., Van Nieuwerburgh, F., Deforce, D., Desmet, T., Beerens, K., and Van Camp, J. (2022). Metabolism and Health Effects of Rare Sugars in a CACO-2\/HepG2 Coculture Model. Nutrients, 14.","DOI":"10.3390\/nu14030611"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sung, J.H., and Kim, R. (2026). In vitro models of the gut-liver axis: What we\u2019ve learned and what remains to be built. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1858289"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110452","DOI":"10.1016\/j.jnutbio.2026.110452","article-title":"Nobiletin ameliorates hepatic insulin resistance by modulating the gut-liver axis","volume":"158","author":"Tang","year":"2026","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.tiv.2014.02.005","article-title":"Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines","volume":"28","author":"Bricks","year":"2014","journal-title":"Toxicol. In Vitro"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.tiv.2003.09.010","article-title":"Feasibility of a simple double-layered coculture system incorporating metabolic processes of the intestine and liver tissue: Application to the analysis of benzo[a]pyrene toxicity","volume":"18","author":"Choi","year":"2004","journal-title":"Toxicol. In Vitro"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108067","DOI":"10.1016\/j.abb.2019.108067","article-title":"Extracellular coenzyme Q10 (CoQ10) is reduced to ubiquinol-10 by intact HepG2 cells independent of intracellular CoQ10 reduction","volume":"672","author":"Takahashi","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41392-022-01125-5","article-title":"Regulation of cholesterol homeostasis in health and diseases: From mechanisms to targeted therapeutics","volume":"7","author":"Duan","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1111\/apt.16602","article-title":"Review article: Therapeutic aspects of bile acid signalling in the gut-liver axis","volume":"54","author":"Simbrunner","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109090","DOI":"10.3748\/wjg.v31.i29.109090","article-title":"Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities","volume":"31","author":"Abdalla","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hoffmann, P., Burmester, M., Langeheine, M., Brehm, R., Empl, M.T., Seeger, B., and Breves, G. (2021). Caco-2\/HT29-MTX co-cultured cells as a model for studying physiological properties and toxin-induced effects on intestinal cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0257824"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"136192","DOI":"10.1016\/j.jhazmat.2024.136192","article-title":"A comprehensive study on the digestion, absorption, and metabolization of tropane alkaloids in human cell models","volume":"480","author":"Faria","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4162\/nrp.2014.8.2.125","article-title":"Black rice extract protected HepG2 cells from oxidative stress-induced cell death via ERK1\/2 and Akt activation","volume":"8","author":"Yoon","year":"2014","journal-title":"Nutr. Res. Pract."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Uberti, F., Trotta, F., Pagliaro, P., Bisericaru, D.M., Cavalli, R., Ferrari, S., Penna, C., and Matencio, A. (2023). Developing new cyclodextrin-based nanosponges complexes to improve vitamin D absorption in an in vitro study. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065322"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.bbrc.2019.06.108","article-title":"Cordycepin alleviates hepatic lipid accumulation by inducing protective autophagy via the PKA\/mTOR pathway","volume":"516","author":"Li","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Guile, M.D., Jain, A., Anderson, K.A., and Clarke, C.F. (2023). New insights on the uptake and trafficking of coenzyme Q. Antioxidants, 12.","DOI":"10.3390\/antiox12071391"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10981","DOI":"10.1039\/D4FO02844A","article-title":"CoQ10 bioaccessibility and Caco-2 cell uptake improved with novel medium-chain triglyceride encapsulation","volume":"15","author":"Li","year":"2024","journal-title":"Food Funct."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lechuga, S., Marino-Melendez, A., Naydenov, N.G., Zafar, A., Braga-Neto, M.B., and Ivanov, A.I. (2024). Regulation of epithelial and endothelial barriers by molecular chaperones. Cells, 13.","DOI":"10.3390\/cells13050370"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00018-012-1070-x","article-title":"Regulation of intestinal epithelial permeability by tight junctions","volume":"70","author":"Suzuki","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/2211068214561025","article-title":"TEER measurement techniques for in vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J. Lab. Autom."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular permeability and tight junction regulation in gut health and disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Steinbauer, S., Wallner, M., Karl, L.M., Gramatte, T., Essl, K., Iken, M., Weghuber, J., Blank-Landeshammer, B., and R\u00f6hrl, C. (2025). Differential enhancement of fat-soluble vitamin absorption and bioefficacy via micellization in combination with selected plant extracts in vitro. Nutrients, 17.","DOI":"10.3390\/nu17020359"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.jnutbio.2014.02.013","article-title":"Proposing a Caco-2\/HepG2 cell model for in vitro iron absorption studies","volume":"25","author":"Scheers","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_61","first-page":"4","article-title":"Recreating gut-liver axis during NAFLD onset by using a Caco-2\/HepG2 co-culture system","volume":"2","author":"Meroni","year":"2022","journal-title":"Metab. Target Organ Damage"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40170-018-0187-2","article-title":"Hepatocellular carcinoma-associated hypercholesterolemia: Involvement of proprotein convertase subtilisin\/kexin type 9 (PCSK9)","volume":"6","author":"Athavale","year":"2018","journal-title":"Cancer Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1021\/acs.jafc.4c10375","article-title":"A Comprehensive Review of Beneficial Effects of Phytosterols on Glycolipid Metabolism and Related Mechanisms","volume":"73","author":"Chen","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"16976","DOI":"10.1021\/acs.jafc.4c03104","article-title":"Lipolysis and Sterol Stability and Bioaccessibility of Wholemeal Rye Bread Enriched with Plant Sterols Subjected to Adult and Elderly Digestion Conditions","volume":"72","author":"Mercatante","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Leng, E., Xiao, Y., Mo, Z., Li, Y., Zhang, Y., Deng, X., Zhou, M., Zhou, C., He, Z., and He, J. (2018). Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2189-6"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.numecd.2019.06.001","article-title":"Differential effects of red yeast rice, Berberis aristata and Morus alba extracts on PCSK9 and LDL uptake","volume":"29","author":"Lupo","year":"2019","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Sundararaman, S.S., D\u00f6ring, Y., and van der Vorst, E.P.C. (2021). PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070793"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.livres.2020.05.001","article-title":"Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis","volume":"4","author":"Chiang","year":"2020","journal-title":"Liver Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Xu, M., Xiao, Y., Yin, J., Hou, W., Yu, X., Shen, L., Liu, F., Wei, L., and Jia, W. (2014). Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103702"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Mantle, D. (2025). Coenzyme Q10 and intracellular signalling pathways: Clinical relevance. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262211024"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1158\/1535-7163.MCT-13-0579","article-title":"The AMPK inhibitor compound C is a potent AMPK-independent antiglioma agent","volume":"13","author":"Liu","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez-Rivero, J.M., Pastor-Maldonado, C.J., de la Mata, M., Villanueva-Paz, M., Povea-Cabello, S., \u00c1lvarez-C\u00f3rdoba, M., Villal\u00f3n-Garc\u00eda, I., Su\u00e1rez-Carrillo, A., Talaver\u00f3n-Rey, M., and Munuera, M. (2019). Atherosclerosis and coenzyme Q. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205195"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Qu, S.L., Li, S.S., Li, D., and Zhao, P.J. (2022). Metabolites and their bioactivities from the genus Cordyceps. Microorganisms, 10.","DOI":"10.3390\/microorganisms10081489"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/hep.31749","article-title":"Cordycepin ameliorates nonalcoholic steatohepatitis by activation of the AMP-activated protein kinase signalling pathway","volume":"74","author":"Lan","year":"2021","journal-title":"Hepatology"},{"key":"ref_75","first-page":"195","article-title":"Total carbohydrates concentration evaluation in products of microbial origin","volume":"76","author":"Alonso","year":"2019","journal-title":"Afinidad"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Galla, R., Mul\u00e8, S., Ferrari, S., Parini, F., Givonetti, A., Cavaletto, M., Miletto, I., Paul, G., Giovenzana, G.B., and Marchese, L. (2025). Non-animal hyaluronic acid from Tremella fuciformis: A new source with a structure and chemical profile comparable to hyaluronic acid. Foods, 14.","DOI":"10.3390\/foods14081362"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.mimet.2014.12.020","article-title":"A high-throughput colorimetric assay of \u03b2-1,3-D-glucans by Congo red dye","volume":"109","author":"Semedo","year":"2015","journal-title":"J. Microbiol. Methods"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.foodchem.2010.12.149","article-title":"A new colorimetric method to quantify \u03b2-1,3-1,6-glucans in comparison with total \u03b2-1,3-glucans in edible mushrooms","volume":"127","author":"Nitschke","year":"2011","journal-title":"Food Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1016\/j.mito.2007.04.002","article-title":"Analysis of coenzyme Q in human blood and tissues","volume":"7","author":"Barshop","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Zhu, Y.Y., Wu, M.M.H., Zhao, Z.C., Gu, F.T., Huang, L.X., Kwok, K.W.H., and Wu, J.Y. (2025). An antioxidative exopolysaccharide-protein complex of Cordyceps Cs-HK1 fungus and its epithelial barrier-protective effects in Caco-2 cell culture. Antioxidants, 14.","DOI":"10.3390\/antiox14121501"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.biocel.2004.11.017","article-title":"Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human Caco-2 cells","volume":"37","author":"Groneberg","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Galla, R., Mul\u00e8, S., Ferrari, S., Grigolon, C., Molinari, C., and Uberti, F. (2024). Palmitoylethanolamide as a supplement: The importance of dose-dependent effects for improving nervous tissue health in an in vitro model. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25169079"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s12272-013-0150-2","article-title":"Monacolin K affects lipid metabolism through the SIRT1\/AMPK pathway in HepG2 cells","volume":"36","author":"Huang","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s12272-014-0502-6","article-title":"HepG2 cells as an in vitro model for evaluation of cytochrome P450 induction by xenobiotics","volume":"38","author":"Choi","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kanmani, P., and Kim, H. (2018). Protective effects of lactic acid bacteria against TLR4-induced inflammatory response in hepatoma HepG2 cells through modulation of toll-like receptor negative regulators of mitogen-activated protein kinase and NF-\u03baB signalling. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01537"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Bort, A., S\u00e1nchez, B.G., Mateos-G\u00f3mez, P.A., D\u00edaz-Laviada, I., and Rodr\u00edguez-Henche, N. (2019). Capsaicin targets lipogenesis in HepG2 cells through AMPK activation, AKT inhibition and PPARs regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071660"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Molinari, C., Morsanuto, V., Ruga, S., Notte, F., Farghali, M., Galla, R., and Uberti, F. (2020). The role of BDNF on aging-modulation markers. Brain Sci., 10.","DOI":"10.3390\/brainsci10050285"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Galla, R., Grisenti, P., Farghali, M., Saccuman, L., Ferraboschi, P., and Uberti, F. (2021). Ovotransferrin supplementation improves iron absorption: An in vitro gastro-intestinal model. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111543"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ejpb.2014.03.017","article-title":"A tunable Caco-2\/HT29-MTX co-culture model mimicking variable permeabilities of the human intestine obtained by an original seeding procedure","volume":"87","author":"Tempesta","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s42255-022-00591-z","article-title":"Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo","volume":"4","author":"Murphy","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Frigerio, J., Tedesco, E., Benetti, F., Insolia, V., Nicotra, G., Mezzasalma, V., Pagliari, S., Labra, M., and Campone, L. (2021). Anticholesterolemic activity of three vegetal extracts (artichoke, caigua, and fenugreek) and their unique blend. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.726199"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Jiao, P., Yang, N., Jia, Q., Fan, B., Feng, K., Yu, J., and Zhao, S. (2025). A dual-reporter LDLR system integrating fluorescence and luminescence for understanding LDLR regulation and facilitating drug discovery. Front. Mol. Biosci., 12.","DOI":"10.3389\/fmolb.2025.1552085"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"H2841","DOI":"10.1111\/1750-3841.13528","article-title":"Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol glucuronides","volume":"81","author":"Shao","year":"2016","journal-title":"J. Food Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.bcp.2009.12.007","article-title":"Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy","volume":"79","author":"Mullen","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6737","DOI":"10.1038\/s41598-018-24935-6","article-title":"Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network","volume":"8","author":"Chae","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/18\/3265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:58:43Z","timestamp":1789473523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/18\/3265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":95,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["molecules31183265"],"URL":"https:\/\/doi.org\/10.3390\/molecules31183265","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}