{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:44:42Z","timestamp":1793285082344,"version":"4.5.0"},"reference-count":99,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1016\/j.phymed.2019.152892","type":"journal-article","created":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T03:12:08Z","timestamp":1552446728000},"page":"152892","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":62,"special_numbering":"C","title":["Berberine and musculoskeletal disorders: The therapeutic potential and underlying molecular mechanisms"],"prefix":"10.1016","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-4551","authenticated-orcid":false,"given":"Sok Kuan","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kok-Yong","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-4102","authenticated-orcid":false,"given":"Soelaiman","family":"Ima-Nirwana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2019.152892_bib0001","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.biopha.2017.08.001","article-title":"Pioglitazone-induced bone loss in diabetic rats and its amelioration by berberine: a portrait of molecular crosstalk","volume":"94","author":"Adil","year":"2017","journal-title":"Biomed. Pharmacother."},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0002","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.phymed.2019.152892_bib0003","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1155\/2011\/959248","article-title":"The molecular pathogenesis of osteosarcoma: a review","volume":"2011","author":"Broadhead","year":"2011","journal-title":"Sarcoma"},{"issue":"7","key":"10.1016\/j.phymed.2019.152892_bib0004","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.joca.2011.04.014","article-title":"Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis","volume":"19","author":"Chan","year":"2011","journal-title":"Osteoarthritis Cartilage"},{"issue":"12","key":"10.1016\/j.phymed.2019.152892_bib0005","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.3390\/ijms17122146","article-title":"Insights on molecular mechanisms of chondrocytes death in osteoarthritis","volume":"17","author":"Charlier","year":"2016","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0006","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/nrd.2016.21","article-title":"Rheumatoid arthritis: current and future trends","volume":"15","author":"Chaudhari","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"issue":"7","key":"10.1016\/j.phymed.2019.152892_bib0007","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/s41419-018-0791-7","article-title":"A novel phosphorylation by AMP-activated kinase regulates RUNX2 from ubiquitination in osteogenesis over adipogenesis","volume":"9","author":"Chava","year":"2018","journal-title":"Cell Death Dis."},{"issue":"3","key":"10.1016\/j.phymed.2019.152892_bib0008","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a026104","article-title":"The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression","volume":"6","author":"Chen","year":"2016","journal-title":"Cold Spring Harb Perspect. Med."},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0009","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1208\/s12249-011-9632-z","article-title":"Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats","volume":"12","author":"Chen","year":"2011","journal-title":"AAPS Pharm. Sci. Tech."},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0010","first-page":"578","article-title":"Berberine induced apoptosis of human osteosarcoma cells by inhibiting phosphoinositide 3 Kinase\/Protein Kinase B (PI3K\/Akt) signal pathway activation","volume":"45","author":"Chen","year":"2016","journal-title":"Iran J. Public Health"},{"key":"10.1016\/j.phymed.2019.152892_bib0011","article-title":"TP53 mutations and survival in osteosarcoma patients: a meta-analysis of published data","volume":"2016","author":"Chen","year":"2016","journal-title":"Dis. Mark."},{"issue":"3","key":"10.1016\/j.phymed.2019.152892_bib0012","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cyto.2009.07.003","article-title":"STAT3 in CD4(+) T helper cell differentiation and inflammatory diseases","volume":"47","author":"Egwuagu","year":"2009","journal-title":"Cytokine"},{"issue":"9","key":"10.1016\/j.phymed.2019.152892_bib0013","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.3109\/03639045.2012.723219","article-title":"Enhancement by sodium caprate and sodium deoxycholate of the gastrointestinal absorption of berberine chloride in rats","volume":"39","author":"Fan","year":"2013","journal-title":"Drug Dev. Ind. Pharm."},{"key":"10.1016\/j.phymed.2019.152892_bib0014","doi-asserted-by":"crossref","first-page":"12155","DOI":"10.1038\/srep12155","article-title":"Transforming berberine into its intestine-absorbable form by the gut microbiota","volume":"5","author":"Feng","year":"2015","journal-title":"Sci. Rep."},{"issue":"Suppl 1(Suppl 1)","key":"10.1016\/j.phymed.2019.152892_bib0015","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/03008200390152188","article-title":"Multiple signaling pathways converge on the Cbfa1\/Runx2 transcription factor to regulate osteoblast differentiation","volume":"44","author":"Franceschi","year":"2003","journal-title":"Connective Tissue Res."},{"issue":"39","key":"10.1016\/j.phymed.2019.152892_bib0016","doi-asserted-by":"crossref","first-page":"33132","DOI":"10.1074\/jbc.M500608200","article-title":"Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression","volume":"280","author":"Gaur","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0017","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1039\/C4MB00500G","article-title":"A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine","volume":"11","author":"Gu","year":"2015","journal-title":"Mol. Biosyst."},{"key":"10.1016\/j.phymed.2019.152892_bib0018","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.phrs.2017.03.002","article-title":"Berberine bioisostere Q8 compound stimulates osteoblast differentiation and function in vitro","volume":"119","author":"Han","year":"2017","journal-title":"Pharmacol Res"},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0019","first-page":"295","article-title":"Berberine alleviates oxidative stress in rats with osteoporosis through receptor activator of NF-kB\/receptor activator of NF-kB ligand\/osteoprotegerin (RANK\/RANKL\/OPG) pathway","volume":"17","author":"He","year":"2017","journal-title":"Bosn. J. Basic Med. Sci."},{"issue":"3","key":"10.1016\/j.phymed.2019.152892_bib0020","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s00774-009-0141-z","article-title":"Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial","volume":"28","author":"Holick","year":"2010","journal-title":"J Bone Miner. Metab."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0021","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejphar.2007.11.013","article-title":"Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-[kappa]B and Akt pathways","volume":"580","author":"Hu","year":"2008","journal-title":"Eur. J Pharmacol."},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0022","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1002\/ptr.3359","article-title":"Protective effects of berberine in an experimental rat osteoarthritis model","volume":"25","author":"Hu","year":"2011","journal-title":"Phytother. Res."},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0023","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1002\/art.30202","article-title":"Berberine induces dendritic cell apoptosis and has therapeutic potential for rheumatoid arthritis","volume":"63","author":"Hu","year":"2011","journal-title":"Arthritis Rheum."},{"issue":"11","key":"10.1016\/j.phymed.2019.152892_bib0024","doi-asserted-by":"crossref","first-page":"26035","DOI":"10.3390\/ijms161125943","article-title":"Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis","volume":"16","author":"Hwang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"issue":"11","key":"10.1016\/j.phymed.2019.152892_bib0025","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/ptr.5693","article-title":"Berberis vulgaris and berberine: an update review","volume":"30","author":"Imenshahidi","year":"2016","journal-title":"Phytother. Res."},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0026","first-page":"671","article-title":"Influence of Palmatine on Bone Metabolism in Ovariectomized Mice and Cytokine Secretion of Osteoblasts","volume":"29","author":"Ishikawa","year":"2015","journal-title":"In Vivo"},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0027","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.smim.2007.10.011","article-title":"Transcriptional regulation of Th17 cell differentiation","volume":"19","author":"Ivanov","year":"2007","journal-title":"Semin. Immunol."},{"key":"10.1016\/j.phymed.2019.152892_bib0028","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature11066","article-title":"AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress","volume":"485","author":"Jeon","year":"2012","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0029","doi-asserted-by":"crossref","first-page":"729","DOI":"10.3892\/or.2016.5327","article-title":"Berberine affects osteosarcoma via downregulating the caspase-1\/IL-1beta signaling axis","volume":"37","author":"Jin","year":"2017","journal-title":"Oncol. Rep."},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0030","doi-asserted-by":"crossref","first-page":"511","DOI":"10.2174\/1871520614666141226124110","article-title":"Berberine exhibits antitumor effects in human ovarian cancer cells","volume":"15","author":"Jin","year":"2015","journal-title":"Anticancer Agents Med. Chem."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/dna.2006.0505","article-title":"Molecular pathogenesis of osteosarcoma","volume":"26","author":"Kansara","year":"2007","journal-title":"DNA Cell Biol."},{"key":"10.1016\/j.phymed.2019.152892_bib0032","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.redox.2016.01.006","article-title":"Molecular regulatory mechanisms of osteoclastogenesis through cytoprotective enzymes","volume":"8","author":"Kanzaki","year":"2016","journal-title":"Redox Biol."},{"issue":"36","key":"10.1016\/j.phymed.2019.152892_bib0033","doi-asserted-by":"crossref","first-page":"33501","DOI":"10.1074\/jbc.M202862200","article-title":"p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation","volume":"277","author":"Kim","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"7","key":"10.1016\/j.phymed.2019.152892_bib0034","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1089\/jwh.2013.4611","article-title":"Osteoporosis prevention, screening, and treatment: a review","volume":"23","author":"Kling","year":"2014","journal-title":"J. Womens Health"},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0035","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/jcb.20958","article-title":"Regulation of osteoblast differentiation by transcription factors","volume":"99","author":"Komori","year":"2006","journal-title":"J. Cell Biochem."},{"key":"10.1016\/j.phymed.2019.152892_bib0036","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1155\/2016\/6145810","article-title":"Enigma of IL-17 and Th17 cells in rheumatoid arthritis and in autoimmune animal models of arthritis","volume":"2016","author":"Kugyelka","year":"2016","journal-title":"Mediators Inflamm."},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0037","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.nutres.2011.03.016","article-title":"Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome","volume":"31","author":"Lamb","year":"2011","journal-title":"Nutr. Res."},{"issue":"8","key":"10.1016\/j.phymed.2019.152892_bib0038","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1359\/jbmr.080325","article-title":"Berberine promotes osteoblast differentiation by Runx2 activation with p38 MAPK","volume":"23","author":"Lee","year":"2008","journal-title":"J. Bone Miner. Res."},{"issue":"10","key":"10.1016\/j.phymed.2019.152892_bib0039","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1248\/bpb.33.1733","article-title":"Palmatine attenuates osteoclast differentiation and function through inhibition of receptor activator of nuclear factor-kappab ligand expression in osteoblast cells","volume":"33","author":"Lee","year":"2010","journal-title":"Biol. Pharm. Bull."},{"issue":"23","key":"10.1016\/j.phymed.2019.152892_bib0040","doi-asserted-by":"crossref","first-page":"8783","DOI":"10.1128\/MCB.20.23.8783-8792.2000","article-title":"Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12","volume":"20","author":"Lee","year":"2000","journal-title":"Mol. Cell Biol."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0041","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1248\/bpb.26.110","article-title":"Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model","volume":"26","author":"Li","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.phymed.2019.152892_bib0042","article-title":"Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus","volume":"2014","author":"Li","year":"2014","journal-title":"Evid. Based Complement Alternat. Med."},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0043","doi-asserted-by":"crossref","first-page":"e66685","DOI":"10.1371\/journal.pone.0066685","article-title":"Mutational analysis of hedgehog signaling pathway genes in human malignant mesothelioma","volume":"8","author":"Lim","year":"2013","journal-title":"PloS one"},{"issue":"12","key":"10.1016\/j.phymed.2019.152892_bib0044","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/nm.2055","article-title":"Modulating hedgehog signaling can attenuate the severity of osteoarthritis","volume":"15","author":"Lin","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.phymed.2019.152892_bib0045","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.fitote.2016.02.001","article-title":"Research progress on berberine with a special focus on its oral bioavailability","volume":"109","author":"Liu","year":"2016","journal-title":"Fitoterapia"},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0046","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.bbrc.2015.02.028","article-title":"Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats","volume":"458","author":"Liu","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0047","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.taap.2015.08.020","article-title":"Berberine attenuates CCN2-induced IL-1beta expression and prevents cartilage degradation in a rat model of osteoarthritis","volume":"289","author":"Liu","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.phymed.2019.152892_bib0048","first-page":"8","article-title":"Update on berberine in nonalcoholic fatty liver disease","volume":"2013","author":"Liu","year":"2013","journal-title":"Evid. Based Complement Alternat. Med."},{"issue":"10","key":"10.1016\/j.phymed.2019.152892_bib0049","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1124\/dmd.110.033936","article-title":"Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats","volume":"38","author":"Liu","year":"2010","journal-title":"Drug Metab. Dispos."},{"issue":"1\u20132","key":"10.1016\/j.phymed.2019.152892_bib0050","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mrfmmm.2008.12.009","article-title":"Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage","volume":"662","author":"Liu","year":"2009","journal-title":"Mutat. Res."},{"issue":"24","key":"10.1016\/j.phymed.2019.152892_bib0051","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.1242\/dev.128.24.5099","article-title":"Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation","volume":"128","author":"Long","year":"2001","journal-title":"Development"},{"key":"10.1016\/j.phymed.2019.152892_bib0052","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/824259","article-title":"Berberine in combination with insulin has additive effects on titanium implants osseointegration in diabetes mellitus rats","volume":"2015","author":"Lu","year":"2015","journal-title":"Evid. Based Complement Alternat. Med."},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0053","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/ar2200","article-title":"Cells of the synovium in rheumatoid arthritis. Dendritic cells","volume":"9","author":"Lutzky","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"10.1016\/j.phymed.2019.152892_bib0054","series-title":"Chapter 35 - The Nature of Osteoporosis Osteoporosis","first-page":"3","author":"Marcus","year":"2001"},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0055","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a008656","article-title":"Caspase functions in cell death and disease","volume":"5","author":"McIlwain","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0056","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/ptr.3353","article-title":"Baekjeolyusin-Tang and its Active Component Berberine Block the Release of Collagen and Proteoglycan from IL-1[beta]-Stimulated Rabbit Cartilage and Down-Regulate Matrix Metalloproteinases in Rabbit Chondrocytes","volume":"25","author":"Moon","year":"2011","journal-title":"PTR, Phytother. Res."},{"issue":"3","key":"10.1016\/j.phymed.2019.152892_bib0057","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1365-2567.2009.03240.x","article-title":"Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease","volume":"129","author":"Onishi","year":"2010","journal-title":"Immunology"},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0058","doi-asserted-by":"crossref","first-page":"436","DOI":"10.4158\/EP.12.4.436","article-title":"Secondary osteoporosis: a review of the recent evidence","volume":"12","author":"Painter","year":"2006","journal-title":"Endocr. Pract."},{"key":"10.1016\/j.phymed.2019.152892_bib0059","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1155\/2015\/905749","article-title":"Application of berberine on treating type 2 diabetes mellitus","volume":"2015","author":"Pang","year":"2015","journal-title":"Int. J. Endocrinol."},{"issue":"10","key":"10.1016\/j.phymed.2019.152892_bib0060","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"},{"issue":"3","key":"10.1016\/j.phymed.2019.152892_bib0061","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1080\/10826076.2012.657731","article-title":"Pharmacokinetic study of berberine from rasont and implication of lysergol for its bioavailability enhancement","volume":"36","author":"Patil","year":"2013","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0062","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.joca.2011.12.018","article-title":"Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development","volume":"20","author":"Pauli","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0063","first-page":"5217","article-title":"Antibacterial activity and mechanism of berberine against Streptococcus agalactiae","volume":"8","author":"Peng","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0064","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1186\/ar4254","article-title":"Linked decreases in liver kinase B1 and AMP-activated protein kinase activity modulate matrix catabolic responses to biomechanical injury in chondrocytes","volume":"15","author":"Petursson","year":"2013","journal-title":"Arthritis Res. Ther."},{"issue":"22","key":"10.1016\/j.phymed.2019.152892_bib0065","first-page":"5258","article-title":"A novel boswellic acids delivery form (Casperome(R)) in the management of musculoskeletal disorders: a review","volume":"21","author":"Riva","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.phymed.2019.152892_bib0066","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3389\/fonc.2017.00296","article-title":"Evaluation of apoptosis and autophagy inducing potential of berberis aristata, azadirachta indica, and their synergistic combinations in parental and resistant human osteosarcoma cells","volume":"7","author":"Sengupta","year":"2017","journal-title":"Front Oncol."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0067","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cellsig.2013.08.046","article-title":"Activation of AMPK protects against hydrogen peroxide-induced osteoblast apoptosis through autophagy induction and NADPH maintenance: new implications for osteonecrosis treatment?","volume":"26","author":"She","year":"2014","journal-title":"Cell Signal"},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0068","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.berh.2018.03.004","article-title":"Wnt signaling as target for the treatment of osteoarthritis","volume":"31","author":"Stampella","year":"2017","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"issue":"6","key":"10.1016\/j.phymed.2019.152892_bib0069","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1136\/annrheumdis-2014-205327","article-title":"Musculoskeletal disorders and the global burden of disease study","volume":"73","author":"Storheim","year":"2014","journal-title":"Ann. Rheum. Dis."},{"issue":"19","key":"10.1016\/j.phymed.2019.152892_bib0070","doi-asserted-by":"crossref","first-page":"19185","DOI":"10.1074\/jbc.M414275200","article-title":"Developmental regulation of Wnt\/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification","volume":"280","author":"Tamamura","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0071","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.toxlet.2015.10.007","article-title":"Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt\/beta-catenin signaling pathway","volume":"240","author":"Tao","year":"2016","journal-title":"Toxicol. Lett."},{"issue":"7","key":"10.1016\/j.phymed.2019.152892_bib0072","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1002\/art.30333","article-title":"Chondrocyte AMP-activated protein kinase activity suppresses matrix degradation responses to proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha","volume":"63","author":"Terkeltaub","year":"2011","journal-title":"Arthritis Rheum."},{"issue":"12","key":"10.1016\/j.phymed.2019.152892_bib0073","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/sctm.17-0137","article-title":"Osteogenic Programming of human mesenchymal stem cells with highly efficient intracellular delivery of RUNX2","volume":"6","author":"Thiagarajan","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"10.1016\/j.phymed.2019.152892_bib0074","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.biopha.2017.02.099","article-title":"Anti-arthritic effect of berberine on adjuvant-induced rheumatoid arthritis in rats","volume":"89","author":"Wang","year":"2017","journal-title":"Biomed. Pharmacother."},{"issue":"7","key":"10.1016\/j.phymed.2019.152892_bib0075","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1258\/ebm.2011.010366","article-title":"Effects of berberine on human rheumatoid arthritis fibroblast-like synoviocytes","volume":"236","author":"Wang","year":"2011","journal-title":"Exp. Biol. Med. (Maywood)"},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0076","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s10753-014-9909-y","article-title":"Berberine ameliorates collagen-induced arthritis in rats associated with anti-inflammatory and anti-angiogenic effects","volume":"37","author":"Wang","year":"2014","journal-title":"Inflammation"},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0077","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3736\/jcim20090408","article-title":"Effects of berberine on differentiation and bone resorption of osteoclasts derived from rat bone marrow cells","volume":"7","author":"Wei","year":"2009","journal-title":"Zhong Xi Yi Jie He Xue Bao"},{"issue":"Suppl 3","key":"10.1016\/j.phymed.2019.152892_bib0078","article-title":"The PI3K\/Akt\/mTOR pathway in innate immune cells: emerging therapeutic applications","volume":"67","author":"Weichhart","year":"2008","journal-title":"Annals Rheumatic Dis."},{"key":"10.1016\/j.phymed.2019.152892_bib0079","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12906-015-0680-x","article-title":"Antifungal activity of berberine hydrochloride and palmatine hydrochloride against Microsporum canis -induced dermatitis in rabbits and underlying mechanism","volume":"15","author":"Xiao","year":"2015","journal-title":"BMC Complement. Altern. Med."},{"key":"10.1016\/j.phymed.2019.152892_bib0080","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.biopha.2018.08.131","article-title":"Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis","volume":"108","author":"Xie","year":"2018","journal-title":"Biomed. Pharmacother."},{"issue":"16","key":"10.1016\/j.phymed.2019.152892_bib0081","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1055\/s-0030-1250040","article-title":"Preventive effects of berberine on glucocorticoid-induced osteoporosis in rats","volume":"76","author":"Xu","year":"2010","journal-title":"Planta Med."},{"key":"10.1016\/j.phymed.2019.152892_bib0082","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/490843","article-title":"Effects and interaction of icariin, curculigoside, and berberine in er-xian decoction, a traditional chinese medicinal formula, on osteoclastic bone resorption","volume":"2012","author":"Xue","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med"},{"issue":"5","key":"10.1016\/j.phymed.2019.152892_bib0083","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.anai.2014.07.021","article-title":"Berberine and limonin suppress IgE production by human B cells and peripheral blood mononuclear cells from food-allergic patients","volume":"113","author":"Yang","year":"2014","journal-title":"Ann. Allergy Asthma Immunol."},{"issue":"7","key":"10.1016\/j.phymed.2019.152892_bib0084","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1089\/dna.2005.24.446","article-title":"Wnt influence on chondrocyte differentiation and cartilage function","volume":"24","author":"Yates","year":"2005","journal-title":"DNA Cell Biol."},{"issue":"46","key":"10.1016\/j.phymed.2019.152892_bib0085","doi-asserted-by":"crossref","first-page":"31972","DOI":"10.1074\/jbc.M109.056838","article-title":"Oxidative stress inhibits insulin-like growth factor-I induction of chondrocyte proteoglycan synthesis through differential regulation of phosphatidylinositol 3-Kinase-Akt and MEK-ERK MAPK signaling pathways","volume":"284","author":"Yin","year":"2009","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0086","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jep.2010.12.013","article-title":"Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in ovariectomized rats","volume":"134","author":"Yogesh","year":"2011","journal-title":"J. Ethnopharmacol."},{"issue":"17","key":"10.1016\/j.phymed.2019.152892_bib0087","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1111\/febs.14147","article-title":"Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut","volume":"284","author":"Yue","year":"2017","journal-title":"FEBS J."},{"key":"10.1016\/j.phymed.2019.152892_bib0088","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cca.2014.12.041","article-title":"PI3K\/Akt signaling in osteosarcoma","volume":"444","author":"Zhang","year":"2015","journal-title":"Clin .Chim. Acta"},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0089","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/jcmm.12186","article-title":"Berberine ameliorates cartilage degeneration in interleukin-1beta-stimulated rat chondrocytes and in a rat model of osteoarthritis via Akt signalling","volume":"18","author":"Zhao","year":"2014","journal-title":"J. Cell Mol. Med."},{"issue":"3","key":"10.1016\/j.phymed.2019.152892_bib0090","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.bbrc.2012.06.045","article-title":"Requirement of the phosphatidylinositol 3-kinase\/Akt signaling pathway for the effect of nicotine on interleukin-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis","volume":"423","author":"Zheng","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"11","key":"10.1016\/j.phymed.2019.152892_bib0091","doi-asserted-by":"crossref","first-page":"27087","DOI":"10.3390\/ijms161125998","article-title":"Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-kappaB and NFAT Pathways","volume":"16","author":"Zhou","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2019.152892_bib0092","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.intimp.2016.02.029","article-title":"Chondroprotective effects of palmatine on osteoarthritis in vivo and in vitro: a possible mechanism of inhibiting the Wnt\/beta-catenin and Hedgehog signaling pathways","volume":"34","author":"Zhou","year":"2016","journal-title":"Int. Immunopharmacol."},{"issue":"2","key":"10.1016\/j.phymed.2019.152892_bib0093","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/j.jss.2011.11.004","article-title":"Berberine inhibits lipopolysaccharide- and polyethylene particle-induced mouse calvarial osteolysis in vivo","volume":"173","author":"Zhou","year":"2012","journal-title":"J. Surg. Res."},{"issue":"10","key":"10.1016\/j.phymed.2019.152892_bib0094","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1080\/03639045.2017.1339076","article-title":"Sustained release effects of berberine-loaded chitosan microspheres on in vitro chondrocyte culture","volume":"43","author":"Zhou","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"issue":"1","key":"10.1016\/j.phymed.2019.152892_bib0095","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.intimp.2015.05.014","article-title":"In vivo anti-apoptosis activity of novel berberine-loaded chitosan nanoparticles effectively ameliorates osteoarthritis","volume":"28","author":"Zhou","year":"2015","journal-title":"Int. Immunopharmacol."},{"issue":"9","key":"10.1016\/j.phymed.2019.152892_bib0096","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s10495-015-1152-y","article-title":"Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling","volume":"20","author":"Zhou","year":"2015","journal-title":"Apoptosis"},{"key":"10.1016\/j.phymed.2019.152892_bib0097","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ejphar.2016.07.027","article-title":"Berberine promotes proliferation of sodium nitroprusside-stimulated rat chondrocytes and osteoarthritic rat cartilage via Wnt\/beta-catenin pathway","volume":"789","author":"Zhou","year":"2016","journal-title":"Eur. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.phymed.2019.152892_bib0098","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.3892\/mmr.2014.2405","article-title":"Berberine induces apoptosis and DNA damage in MG-63 human osteosarcoma cells","volume":"10","author":"Zhu","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.phymed.2019.152892_bib0099","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/aps.2016.125","article-title":"Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system","volume":"38","author":"Zou","year":"2016","journal-title":"Acta Pharmacol. Sin"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711319300625?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711319300625?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:22:38Z","timestamp":1760552558000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711319300625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":99,"alternative-id":["S0944711319300625"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2019.152892","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Berberine and musculoskeletal disorders: The therapeutic potential and underlying molecular mechanisms","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2019.152892","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"152892"}}