{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:25:52Z","timestamp":1782797152296,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673941"],"award-info":[{"award-number":["81673941"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2021,4,19]]},"abstract":"Total flavonoids of Rhizoma Drynariae (TFRD) have been shown to have beneficial effects on osteoarthritis (OA) clinically, but the mechanisms have not been elucidated. In this study, we investigated the effect of TFRD on articular cartilage in an OA rat model established by the Hulth method and in SW1353 chondrocytes induced by the proinflammatory factor interleukin-1\u03b2 (IL-1\u03b2). The results showed that TFRD could alleviate the pathological changes in knee cartilage in OA model rats. In vivo, the qPCR analysis indicated that the mRNA levels of matrix metalloproteinases, MMP-1, MMP-3, and MMP-13, were decreased, while tissue inhibitor of matrix metalloproteinases- (TIMP-) 4 was increased in cartilage, and these changes could be partially prevented by TFRD. In vitro experiments showed that IL-1\u03b2 could significantly increase the expression of MMP-1, MMP-3, and MMP-13 and decrease the expression of TIMP-4 in SW1353 cells at the mRNA and protein levels. TFRD could increase the expression of MMP-3 and MMP-13 and decrease the expression of TIMP-4. Transfection of siRNA and addition of pathway inhibitors were used to clarify that inhibition of NF-\n \n \u03ba<\/a:mi>\n B<\/a:mi>\n <\/a:math>\n <\/jats:inline-formula> and PI3K\/AKT pathway decreased MMP-1, MMP-3, and MMP-13 and increased TIMP-4 expression. We also found that in IL-1\u03b2-induced SW1353 cells, TFRD pretreatment had a modest inhibitory effect on p-AKT (Ser473) and reversed the increase of nuclear factor kappa-B (NF-\n \n \u03ba<\/c:mi>\n B<\/c:mi>\n <\/c:math>\n <\/jats:inline-formula>) p65 in nuclear fraction and the decrease of inhibitor of NF-\n \n \u03ba<\/e:mi>\n B<\/e:mi>\n <\/e:math>\n <\/jats:inline-formula>\n \n \n \n \n I<\/g:mi>\n \u03ba<\/g:mi>\n B<\/g:mi>\n <\/g:mrow>\n <\/g:mfenced>\n <\/g:math>\n <\/jats:inline-formula>-\n \n \u03b1<\/l:mi>\n <\/l:math>\n <\/jats:inline-formula> in the cytosolic fraction. Further immunofluorescence confirmed that TFRD can inhibit IL-1\u03b2-induced NF-\n \n \u03ba<\/n:mi>\n B<\/n:mi>\n <\/n:math>\n <\/jats:inline-formula> p65 translocation to the nucleus to some extent. In conclusion, TFRD showed chondroprotective effects by restoring the MMP\/TIMP balance in OA models by suppressing the activation of the NF-\n \n \u03ba<\/p:mi>\n B<\/p:mi>\n <\/p:math>\n <\/jats:inline-formula> and PI3K\/AKT pathways.<\/jats:p>","DOI":"10.1155\/2021\/6634837","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T19:58:10Z","timestamp":1619035090000},"page":"1-14","source":"Crossref","is-referenced-by-count":12,"title":["Total Flavonoids of Rhizoma Drynariae Restore the MMP\/TIMP Balance in Models of Osteoarthritis by Inhibiting the Activation of the NF-\n \u03ba<\/a:mi>\n B<\/a:mi>\n <\/a:math> and PI3K\/AKT Pathways"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-289X","authenticated-orcid":true,"given":"Guang-Yao","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-5450","authenticated-orcid":true,"given":"Jia-Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-1197","authenticated-orcid":true,"given":"Xiao-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3189-4775","authenticated-orcid":true,"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-2168","authenticated-orcid":true,"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-349X","authenticated-orcid":true,"given":"Yi-Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-9238","authenticated-orcid":true,"given":"Tong-Liang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-9020","authenticated-orcid":true,"given":"Ze-Ran","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-0058","authenticated-orcid":true,"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9163-8426","authenticated-orcid":true,"given":"Qing-Wen","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China"},{"name":"Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(19)30417-9"},{"key":"2","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.3389\/fimmu.2017.01745","article-title":"Aging, obesity, and inflammatory age-related diseases","volume":"8","author":"D. Frasca","year":"2019","journal-title":"Frontiers in Immunology"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703856114"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-019-1391-7"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116786"},{"key":"6","first-page":"73","article-title":"Biochemical and biological attributes of matrix metalloproteinases","volume":"114","author":"N. Cui","year":"2017","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.04.004"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.3390\/nu9091022"},{"key":"9","article-title":"Inflammatory cytokines via up-regulation of aquaporins deteriorated the pathogenesis of early osteoarthritis","volume":"14","author":"C. Tan","year":"2019","journal-title":"PLoS One"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00431"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.06.011"},{"key":"12","doi-asserted-by":"crossref","first-page":"j1909","DOI":"10.1136\/bmj.j1909","article-title":"Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data","volume":"357","author":"M. Bally","year":"2017","journal-title":"British Medical Journal"},{"key":"13","article-title":"Insights into the action mechanisms of traditional Chinese medicine in osteoarthritis","volume":"2017","author":"L. Li","year":"2017","journal-title":"Evidence-Based Complementary and Alternative Medicine"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s139804"},{"issue":"2","key":"15","first-page":"77","article-title":"Clinical observation of total flavonoids of Rhizoma Drynariae in the patients with keen osteoarthritis","volume":"8","author":"R. K. Zhou","year":"2011","journal-title":"China Medical Herald"},{"issue":"4","key":"16","first-page":"254","article-title":"Optimization of macroporous resin in separation of total flavonoids from rhizoma Drynariae","volume":"4","author":"Z. H. Zhao","year":"2009","journal-title":"World Journal of Integrated Traditional and Western Medicine"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.3109\/17453677008991540"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100100107"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0632-0"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711300304"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1482"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1111\/os.12409"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01502-0"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6312"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1002\/art.11433"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17081350"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21283"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239181"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.04.008"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.08.018"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2218"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.2217\/17520363.2.4.409"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.3892\/or.2019.7442"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2017.1411474"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20190043"},{"issue":"8","key":"36","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.3390\/ijms19082308","article-title":"Sargassum serratifolium extract attenuates interleukin-1\u03b2-induced oxidative stress and inflammatory response in chondrocytes by suppressing the activation of NF-\u03baB, p38 MAPK, and PI3K\/akt","volume":"19","author":"P. Cheol","year":"2018","journal-title":"International Journal of Molecular Sciences"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/6634837.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/6634837.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/6634837.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T19:58:23Z","timestamp":1619035103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ecam\/2021\/6634837\/"}},"subtitle":[],"editor":[{"given":"Andreas","family":"Sandner Kiesling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":36,"alternative-id":["6634837","6634837"],"URL":"https:\/\/doi.org\/10.1155\/2021\/6634837","relation":{},"ISSN":["1741-4288","1741-427X"],"issn-type":[{"value":"1741-4288","type":"electronic"},{"value":"1741-427X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}