{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:15:54Z","timestamp":1788470154463,"version":"build-2803163510"},"reference-count":76,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Science Centre, Poland","award":["2016\/23\/B\/NZ9\/03629"],"award-info":[{"award-number":["2016\/23\/B\/NZ9\/03629"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone mass loss occurs with a decrease in osteoblast proliferation and differentiation, or the enhancement of bone resorption, which further leads to the impairment of bone mineral density and increase in bone fracture. Recent studies suggest that some phenolic compounds found in food play positive role in bone metabolism. High content of phenolic compounds with potential beneficial effects on bone metabolism have been identified in the Viburnum opulus fruit. The aim of the study was to determine the influence of V. opulus fresh juice (FJ) and juice purified by solid phase extraction (PJ) on osteogenesis processes with osteosarcoma Saos-2 cell lines. V. opulus purified juice revealed stronger potential as an inducer of Saos-2 osteogenic differentiation. Saos-2 cells matrix mineralization was evaluated with alkaline phosphatase (ALP) activity measurement and alizarin red S staining. Gene expression analysis showed the elevation of the mRNA levels of Runt-related transcription factor 2 (RUNX2), ALP, collagen type 1 and osteonectin, whereas the nuclear factor-\u03baB ligand and osteoprotegerin ratio (RANKL\/OPG) decreased. Furthermore, V. opulus was able to diminish the secretion of pro-inflammatory cytokines Il6 and TNF\u03b1, however had no effect on vascular endothelial growth factor (VEGF). It decreased intracellular oxidative stress and induced DNA repair, but had no effect on the growth inhibition of lactic acid beneficial microorganisms.<\/jats:p>","DOI":"10.3390\/ijms21144909","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"4909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Viburnum opulus L. Juice Phenolic Compounds Influence Osteogenic Differentiation in Human Osteosarcoma Saos-2 Cells"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-1654","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Zak\u0142os-Szyda","sequence":"first","affiliation":[{"name":"Institute of Molecular and Industrial Biotechnology, Department of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4\/10, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1865-4833","authenticated-orcid":false,"given":"Adriana","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Environmental Biotechnology, Lodz University of Technology, W\u00f3lcza\u0144ska 171\/173, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3279-0612","authenticated-orcid":false,"given":"Nina","family":"Pietrzyk","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Industrial Biotechnology, Department of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4\/10, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-4818","authenticated-orcid":false,"given":"Anna","family":"Pods\u0119dek","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Industrial Biotechnology, Department of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4\/10, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.11138\/ccmbm\/2017.14.1.209","article-title":"Oxidative stress in bone remodeling: Role of antioxidants","volume":"14","author":"Domazetovic","year":"2017","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"494","DOI":"10.3389\/fendo.2019.00494","article-title":"Modulatory effects of plant polyphenols on bone remodeling: A prospective view from the bench to bedside","volume":"10","author":"Nicolin","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6882-14-29","article-title":"Potential anti-osteoporotic effects of herbal extracts on osteoclasts, osteoblasts and chondrocytes in vitro","volume":"14","author":"Mukudai","year":"2014","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100216","DOI":"10.1016\/j.bonr.2019.100216","article-title":"An insight into the paradigms of osteoporosis: From genetics to biomechanics","volume":"11","author":"Taha","year":"2019","journal-title":"Bone Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Komori, T. (2019). Regulation of proliferation, differentiation and functions of osteoblasts by runx2. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071694"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1002\/jcp.29131","article-title":"Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway","volume":"235","author":"Zhu","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"706","DOI":"10.14348\/molcells.2017.0225","article-title":"Current understanding of RANK signaling in osteoclast differentiation and maturation","volume":"40","author":"Park","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00223-015-9954-z","article-title":"High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment","volume":"96","author":"Shu","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1749-799X-6-30","article-title":"Effects of obesity on bone metabolism","volume":"6","author":"Cao","year":"2011","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.3389\/fimmu.2019.01001","article-title":"Effects of sweet cherry polyphenols on enhanced osteoclastogenesis associated with childhood obesity","volume":"10","author":"Corbo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.3945\/jn.108.100032","article-title":"Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese mice","volume":"139","author":"Kyung","year":"2009","journal-title":"J. Nutr."},{"key":"ref_12","first-page":"1","article-title":"Evaluation of osteogenesis and angiogenesis of icariin in local controlled release and systemic delivery for calvarial defect in ovariectomized rats","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_13","unstructured":"WHO (2016). Library Global Report on Diabetes, WHO Press."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5812401","DOI":"10.1155\/2017\/5812401","article-title":"Effects of polyphenol intake on metabolic syndrome: Current evidences from human trials","volume":"2017","author":"Badimon","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1007\/s00125-015-3592-x","article-title":"Polyphenol-rich diets improve glucose metabolism in people at high cardiometabolic risk: A controlled randomised intervention trial","volume":"58","author":"Bozzetto","year":"2015","journal-title":"Diabetologia"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sequeira, I.R., and Poppitt, S.D. (2017). Unfolding novel mechanisms of polyphenol flavonoids for better glycaemic control: Targeting pancreatic islet amyloid polypeptide (IAPP). Nutrients, 9.","DOI":"10.3390\/nu9070788"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2174\/1874070701812010219","article-title":"Polyphenols as Suitable Control for Obesity and Diabetes","volume":"12","author":"Mihaylova","year":"2018","journal-title":"Open Biotechnol. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s11101-017-9529-x","article-title":"Molecular signaling mechanisms behind polyphenol-induced bone anabolism","volume":"16","author":"Torre","year":"2017","journal-title":"Phytochem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kang, G.G., Francis, N., Hill, R., Waters, D., Blanchard, C., and Santhakumar, A.B. (2020). Dietary polyphenols and gene expression in molecular pathways associated with type 2 diabetes mellitus: A review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010140"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Austermann, K., Baecker, N., Stehle, P., and Heer, M. (2019). Putative effects of nutritive polyphenols on bone metabolism in vivo\u2014Evidence from human studies. Nutrients, 11.","DOI":"10.3390\/nu11040871"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/jmf.2015.0045","article-title":"Soy isoflavones and osteoporotic bone loss: A review with an emphasis on modulation of bone remodeling","volume":"19","author":"Zheng","year":"2016","journal-title":"J. Med. Food"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zak\u0142os-Szyda, M., Budryn, G., Grzelczyk, J., Perez-Sanchez, H., and \u017by\u017celewicz, D. (2020). Evaluation of Isoflavones as bone resorption inhibitors upon interactions with receptor activator of nuclear factor-\u03bab ligand (RANKL). Molecules, 25.","DOI":"10.3390\/molecules25010206"},{"key":"ref_23","first-page":"1721","article-title":"Polyphenols from grape pomace induce osteogenic differentiation in mesenchymal stem cells","volume":"45","author":"Torre","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zak\u0142os-Szyda, M., Pawlik, N., Polka, D., Nowak, A., Kozio\u0142kiewicz, M., and Pods\u0119dek, A. (2019). Viburnum opulus fruit phenolic compounds as cytoprotective agents able to decrease free fatty acids and glucose uptake by Caco-2 cells. Antioxidants, 8.","DOI":"10.3390\/antiox8080262"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.2174\/1568026615666150619143051","article-title":"Antidiabetic effect of polyphenolic extracts from selected edible plants as \u03b1-amylase, \u03b1-glucosidase and PTP1B inhibitors, and \u03b2 pancreatic cells cytoprotective agents\u2014A comparative study","volume":"15","author":"Majewska","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_26","first-page":"33","article-title":"The influence of Viburnum opulus polyphenolic compounds on metabolic activity and migration of HeLa and MCF cells","volume":"33","author":"Pawlik","year":"2019","journal-title":"Acta Innov."},{"key":"ref_27","first-page":"2","article-title":"Cellular and animal models for the identification of osteoporosis determinants increasing vertebral compression fractures risk","volume":"3","author":"Act","year":"2015","journal-title":"Osteoporos. Phys. Act."},{"key":"ref_28","first-page":"864","article-title":"Biochemical and agro-biological diversity of Viburnum opulus genotypes","volume":"5","author":"Daubaras","year":"2010","journal-title":"Cent. Eur. J. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.3390\/nu12072003","article-title":"Viburnum opulus L. juice phenolics inhibit mouse 3T3-L1 cells adipogenesis and pancreatic lipase activity","volume":"12","author":"Pietrzyk","year":"2020","journal-title":"Nutrients"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zak\u0142os-Szyda, M., Kowalska-Baron, A., Pietrzyk, N., and Drzazga, A. (2020). Evaluation of Viburnum opulus L. fruit phenolics cytoprotective potential on insulinoma MIN6 cells relevant for diabetes mellitus and obesity. Antioxidants, 9.","DOI":"10.3390\/antiox9050433"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Min, J., Yuan, Z., Zhang, Q., Lin, S., Wang, K., and Luo, J. (2018). Analysis of anti-osteoporosis function of chlorogenic acid by gene microarray profiling in ovariectomy rat model. Biosci. Rep., 38.","DOI":"10.1042\/BSR20180775"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/s11094-014-1105-8","article-title":"Biologically active substances from european guelder berry fruits","volume":"48","author":"Perova","year":"2014","journal-title":"Pharm. Chem. J."},{"key":"ref_33","first-page":"e20180014","article-title":"Stanozolol promotes osteogenic gene expression and apposition of bone mineral in vitro Abstract","volume":"27","author":"Ghiacci","year":"2019","journal-title":"J. Appl. Oral Serv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00223-014-9879-y","article-title":"SaOS2 osteosarcoma cells as an in vitro model for studying the transition of human osteoblasts to osteocytes","volume":"95","author":"Prideaux","year":"2014","journal-title":"Calcif. Tissue Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jnutbio.2017.09.014","article-title":"Select polyphenolic fractions from dried plum enhance osteoblast activity through BMP-2 signaling","volume":"55","author":"Graef","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10068-013-0055-3","article-title":"Chlorogenic acid promotes osteoblastogenesis in human adipose tissue-derived mesenchymal stem cells","volume":"22","author":"Bin","year":"2013","journal-title":"Food Sci. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, B., Lee, S., Song, S., Kim, W.H., Song, E., Lee, J., Lee, S., Han, D., and Lee, J. (2019). Protective effects of melon extracts on bone strength, mineralization, and metabolism in rats with ovariectomy-induced osteoporosis. Antioxidants, 8.","DOI":"10.3390\/antiox8080306"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhou, R.P., Lin, S.J., Wan, W.B., Zuo, H.L., Yao, F.F., Ruan, H.B., Xu, J., Song, W., Zhou, Y.C., and Wen, S.Y. (2016). Chlorogenic acid prevents osteoporosis by Shp2\/PI3K\/Akt pathway in ovariectomized rats. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166751"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9926","DOI":"10.1074\/jbc.M113.522870","article-title":"(\u2212)-Epicatechin gallate (ECG) stimulates osteoblast differentiation via runt-related transcription factor 2 (RUNX2) and transcriptional coactivator with PDZ-binding motif (TAZ)-mediated transcriptional activation","volume":"289","author":"Byun","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kovar, H., Bierbaumer, L., and Radic-sarikas, B. (2020). The YAP\/TAZ pathway in osteogenesis and bone sarcoma pathogenesis. Cells, 9.","DOI":"10.3390\/cells9040972"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cmet.2019.10.003","article-title":"TAZ is a negative regulator of PPAR\u03b3 activity in adipocytes and TAZ deletion improves insulin sensitivity and glucose tolerance","volume":"31","author":"Isaac","year":"2020","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lin, S.Y., Kang, L., Wang, C.Z., Huang, H.H., Cheng, T.L., Huang, H.T., Lee, M.J., Lin, Y.S., Ho, M.L., and Wang, G.J. (2018). (\u2212)-Epigallocatechin-3-gallate (EGCG) enhances osteogenic differentiation of human bone marrow mesenchymal stem cells. Molecules, 23.","DOI":"10.3390\/molecules23123221"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4248\/BR201301003","article-title":"Osteoclasts: New Insights","volume":"1","author":"Feng","year":"2013","journal-title":"Bone Research"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Shin, J., Kim, J.E., Pak, K.J., Kang, J.I., Kim, T.S., Lee, S.Y., Yeo, I.H., Park, J.H.Y., Kim, J.H., and Kang, N.J. (2017). A combination of soybean and Haematococcus extract alleviates ultraviolet B-induced photoaging. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030682"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, S.T., Kang, L., Wang, C.Z., Huang, P.J., Huang, H.T., Lin, S.Y., Chou, S.H., Lu, C.C., Shen, P.C., and Lin, Y.S. (2019). (\u2212)-Epigallocatechin-3-gallate decreases osteoclastogenesis via modulation of RANKL and osteoprotegrin. Molecules, 24.","DOI":"10.3390\/molecules24010156"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1248\/bpb.b13-00430","article-title":"Chlorogenic acid inhibits osteoclast differentiation and bone resorption by down-regulation of receptor activator of nuclear factor kappa-b ligand-induced nuclear factor of activated t cells c1 expression","volume":"36","author":"Kwak","year":"2013","journal-title":"Biol. Pharm. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"579305","DOI":"10.1155\/2014\/579305","article-title":"Antiosteoporotic effect of combined extract of morus alba and polygonum odoratum","volume":"2014","author":"Sungkamanee","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"364604","DOI":"10.1155\/2012\/364604","article-title":"Potential antiosteoporotic agents from plants: A comprehensive review","volume":"2012","author":"Jia","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbrc.2003.12.073","article-title":"Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-\u03baB","volume":"314","author":"Bai","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2131\/jts.39.803","article-title":"Grape seed proanthocyanidins inhibit H2O2-induced osteoblastic MC3T3-E1 cell apoptosis via ameliorating H2O2-induced mitochondrial dysfunction","volume":"39","author":"Zhang","year":"2014","journal-title":"J. Toxicol. Sci."},{"key":"ref_51","first-page":"1","article-title":"The Preventive effect of biochanin a on bone loss in ovariectomized rats: Involvement in regulation of growth and activity of osteoblasts and osteoclasts","volume":"2013","author":"Su","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1039\/C5FO01222H","article-title":"Comparison of black, green and rooibos tea on osteoblast activity","volume":"7","author":"Nash","year":"2016","journal-title":"Food Funct."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2016.12.010","article-title":"Obesity is a concern for bone health with aging","volume":"39","author":"Claudia","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Liang, N., and Kitts, D.D. (2016). Role of chlorogenic acids in controlling oxidative and inflammatory stress conditions. Nutrients, 8.","DOI":"10.3390\/nu8010016"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bone.2014.09.017","article-title":"Bringing new life to damaged bone: The importance of angiogenesis in bone repair and regeneration","volume":"70","author":"Stegen","year":"2015","journal-title":"Bone"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s13402-014-0216-2","article-title":"Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1\u03b1\/AKT pathway","volume":"38","author":"Park","year":"2015","journal-title":"Cell. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1002\/mnfr.201500407","article-title":"Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity","volume":"59","author":"Ana","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11056","DOI":"10.1002\/jcb.28383","article-title":"Phenolic and anthocyanin fractions from wild blueberries (V. angustifolium) differentially modulate endothelial cell migration partially through RHOA and RAC1","volume":"120","author":"Tsakiroglou","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wang, A., Leong, D.J., He, Z., Xu, L., Liu, L., Kim, S.J., Hirsh, D.M., Hardin, J.A., Cobelli, N.J., and Sun, H.B. (2016). Procyanidins mitigate osteoarthritis pathogenesis by, at least in part, suppressing vascular endothelial growth factor signaling. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122065"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Farah, A., and dePaula Lima, J. (2019). Consumption of chlorogenic acids through coffee and health implications. Beverages, 5.","DOI":"10.3390\/beverages5010011"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.3945\/jn.108.095554","article-title":"Chlorogenic Acids from Green Coffee Extract are Highly Bioavailable in Humans","volume":"138","author":"Farah","year":"2008","journal-title":"J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Clifford, M.N., Kerimi, A., and Williamson, G. (2020). Bioavailability and metabolism of chlorogenic acids (acyl-quinic acids) in humans. Compr. Rev. Food Sci. Food Saf., 1\u201354.","DOI":"10.1111\/1541-4337.12518"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"895","DOI":"10.18388\/abp.2015_1154","article-title":"The impact of polyphenols on Bifidobacterium growth","volume":"62","author":"Gwiazdowska","year":"2015","journal-title":"Acta Biochim. Pol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3389\/fmicb.2019.00829","article-title":"Antibacterial properties of polyphenols: Characterization and QSAR (Quantitative structure-activity relationship) models","volume":"10","author":"Forquet","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"103861","DOI":"10.1016\/j.jff.2020.103861","article-title":"Proanthocyanidins in grape seeds: An updated review of their health benefits and potential uses in the food industry","volume":"67","author":"Unusan","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biopha.2017.10.064","article-title":"Chlorogenic acid (CGA): A pharmacological review and call for further research","volume":"97","author":"Naveed","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jfda.2018.01.002","article-title":"Benefaction of probiotics for human health: A review","volume":"26","author":"Patra","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/fsn3.868","article-title":"Chlorogenic acid alleviates obesity and modulates gut microbiota in high-fed mice","volume":"7","author":"Wang","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1080\/19490976.2017.1371893","article-title":"Mechanisms of gut microbiota-mediated bone remodeling","volume":"9","author":"Yan","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_70","first-page":"1","article-title":"The effect of probiotic bacteria on transepithelial calcium transport and calcium uptake in human intestinal-like caco-2 cells","volume":"7","author":"Gilman","year":"2006","journal-title":"Curr. Issues Intest. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/jcpe.12838","article-title":"Probiotic Lactobacillus rhamnosus GG prevents alveolar bone loss in a mouse model of experimental periodontitis","volume":"45","author":"Gatej","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/boneres.2017.46","article-title":"Intestinal microbiota: A potential target for the treatment of postmenopausal osteoporosis","volume":"5","author":"Xu","year":"2017","journal-title":"Bone Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1093\/rheumatology\/kez302","article-title":"Gut microbiota alterations associated with reduced bone mineral density in older adults","volume":"58","author":"Das","year":"2019","journal-title":"Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e00810","DOI":"10.1002\/mbo3.810","article-title":"Microbial osteoporosis: The interplay between the gut microbiota and bones via host metabolism and immunity","volume":"8","author":"Li","year":"2019","journal-title":"Microbiologyopen"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.yrtph.2015.09.021","article-title":"Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens","volume":"73","author":"Nowak","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/jcb.23016","article-title":"Effects of Cissus quadrangularis on the Proliferation, differentiation and matrix mineralization of human osteoblast like SaOS-2 Cells","volume":"1045","author":"Muthusami","year":"2011","journal-title":"J. Cell. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:22Z","timestamp":1760176222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,11]]},"references-count":76,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ijms21144909"],"URL":"https:\/\/doi.org\/10.3390\/ijms21144909","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,11]]}}}