{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:45:59Z","timestamp":1790131559270,"version":"4.0.1"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Technology development Program of the Ministry of SMEs and Startups","award":["S2910765"],"award-info":[{"award-number":["S2910765"]}]},{"name":"National Research Foundation of Korea (NRF) grant","award":["2020R1I1A1A01072353"],"award-info":[{"award-number":["2020R1I1A1A01072353"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1\u03b2)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1\u03b2-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms22062987","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T11:38:58Z","timestamp":1615808338000},"page":"2987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Antiosteoarthritic Effect of Morroniside in Chondrocyte Inflammation and Destabilization of Medial Meniscus-Induced Mouse Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-5531","authenticated-orcid":false,"given":"Eunkuk","family":"Park","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2031-0802","authenticated-orcid":false,"given":"Chang Gun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Jae","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"},{"name":"Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hee","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seokjin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoju","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-9779","authenticated-orcid":false,"given":"Jeonghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Whan","family":"Choi","sequence":"additional","affiliation":[{"name":"Natural Products Research Institute, Gyeonggi Institute of Science &amp; Technology Promotion, Suwon 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6374-0140","authenticated-orcid":false,"given":"Siyoung","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"},{"name":"Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-3530","authenticated-orcid":false,"given":"Seon-Yong","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"Barr","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s13075-016-1189-5","article-title":"Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats","volume":"18","author":"Fusco","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-981-13-3681-2_6","article-title":"Ageing and osteoarthritis","volume":"91","author":"Sacitharan","year":"2019","journal-title":"Subcell. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rim, Y.A., and Ju, J.H. (2020). The role of fibrosis in osteoarthritis progression. Life, 11.","DOI":"10.3390\/life11010003"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110023","DOI":"10.1016\/j.biopha.2020.110023","article-title":"Protective effect of a new hyaluronic acid-carnosine conjugate on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis","volume":"125","author":"Impellizzeri","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1016\/j.lfs.2005.05.052","article-title":"The effect of IL-1\u03b2 on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes","volume":"77","author":"Aida","year":"2005","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R58","DOI":"10.1186\/ar4494","article-title":"p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis","volume":"16","author":"Philipot","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.biopha.2018.09.161","article-title":"Luteolin inhibits IL-1\u03b2-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model","volume":"109","author":"Fei","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jimi, E., Fei, H., and Nakatomi, C. (2019). NF-\u03baB signaling regulates physiological and pathological chondrogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246275"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Park, C., Jeong, J.W., Lee, D.S., Yim, M.J., Lee, J.M., Han, M.H., Kim, S., Kim, H.S., Kim, G.Y., and Park, E.K. (2018). 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. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082308"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2174\/1573397113666170829155149","article-title":"Current treatment options for osteoarthritis","volume":"14","author":"Hermann","year":"2018","journal-title":"Curr. Rheumatol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1136\/bmjebm-2019-111213","article-title":"Paracetamol as first line for treatment of knee and hip osteoarthritis","volume":"25","author":"Onakpoya","year":"2020","journal-title":"BMJ Evid. Based Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lindler, B.N., Long, K.E., Taylor, N.A., and Lei, W. (2020). Use of herbal medications for treatment of osteoarthritis and rheumatoid arthritis. Medicines, 7.","DOI":"10.3390\/medicines7110067"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Patel, J., Ladani, A., Sambamoorthi, N., LeMasters, T., Dwibedi, N., and Sambamoorthi, U. (2021). A machine learning approach to identify predictors of potentially inappropriate non-steroidal anti-inflammatory drugs (NSAIDs) use in older adults with osteoarthritis. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18010155"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1111\/bcp.13656","article-title":"Long-term adverse effects of paracetamol\u2014A review","volume":"84","author":"McCrae","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tran, N., Pham, B., and Le, L. (2020). Bioactive compounds in anti-diabetic plants: From herbal medicine to modern drug discovery. Biology, 9.","DOI":"10.3390\/biology9090252"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Britti, D., Crupi, R., Impellizzeri, D., Gugliandolo, E., Fusco, R., Schievano, C., Morittu, V.M., Evangelista, M., Di Paola, R., and Cuzzocrea, S. (2017). A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models. BMC Vet. Res., 13.","DOI":"10.1186\/s12917-017-1151-z"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fusco, R., Siracusa, R., Peritore, A.F., Gugliandolo, E., Genovese, T., D\u2019Amico, R., Cordaro, M., Crupi, R., Mandalari, G., and Impellizzeri, D. (2020). The role of cashew (Anacardium occidentale L.) nuts on an experimental model of painful degenerative joint disease. Antioxidants, 9.","DOI":"10.3390\/antiox9060511"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gugliandolo, E., Peritore, A.F., Impellizzeri, D., Cordaro, M., Siracusa, R., Fusco, R., D\u2019Amico, R., Di Paola, R., Schievano, C., and Cuzzocrea, S. (2020). Dietary supplementation with palmitoyl-glucosamine co-micronized with curcumin relieves osteoarthritis pain and benefits joint mobility. Animals, 10.","DOI":"10.3390\/ani10101827"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.jchromb.2011.01.022","article-title":"Analysis of the interactions of multicomponents in Cornus officinalis Sieb. et Zucc. with human serum albumin using on-line dialysis coupled with HPLC","volume":"879","author":"Liu","year":"2011","journal-title":"J. Chromatogr. B"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tian, W., Zhao, J., Lee, J.H., Akanda, M.R., Cho, J.H., Kim, S.K., Choi, Y.J., and Park, B.Y. (2019). Neuroprotective effects of Cornus officinalis on stress-induced hippocampal deficits in rats and H2O2-induced neurotoxicity in SH-SY5Y neuroblastoma cells. Antioxidants, 9.","DOI":"10.3390\/antiox9010027"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ji, L.L., Wang, X., Li, J.J., Zhong, X.J., Zhang, B., Juan, J., and Shang, X.Y. (2019). New iridoid derivatives from the fruits of Cornus officinalis and their neuroprotective activities. Molecules, 24.","DOI":"10.3390\/molecules24030625"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1142\/S0192415X14500736","article-title":"Selective therapeutic effect of Cornus officinalis fruits on the damage of different organs in STZ-induced diabetic rats","volume":"42","author":"Han","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"121","DOI":"10.11005\/jbm.2012.19.2.121","article-title":"Effect of Cornus officinalis on receptor activator of nuclear factor-\u03baB ligand (RANKL)-induced osteoclast differentiation","volume":"19","author":"Kim","year":"2012","journal-title":"J. Bone Metab."},{"key":"ref_25","first-page":"461","article-title":"Anti-Inflammatory effect of Cornus officinalis fruit extract for potential of cosmetic ingredient","volume":"13","author":"Lee","year":"2015","journal-title":"Kor. J. Aesthet. Cosmetol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-016-1172-3","article-title":"Antioxidant activities and oxidative stress inhibitory effects of ethanol extracts from Cornus officinalis on raw 264.7 cells","volume":"16","author":"Hwang","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Quah, Y., Lee, S.J., Lee, E.B., Birhanu, B.T., Ali, M.S., Abbas, M.A., Boby, N., Im, Z.E., and Park, S.C. (2020). Cornus officinalis ethanolic extract with potential anti-allergic, anti-inflammatory, and antioxidant activities. Nutrients, 12.","DOI":"10.3390\/nu12113317"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Park, S., Moon, B.R., Kim, J.E., Kim, H.J., and Zhang, T. (2020). Aqueous extracts of Morus alba root Bark and Cornus officinalis fruit protect against osteoarthritis symptoms in testosterone-deficient and osteoarthritis-induced rats. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121245"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/10408398.2011.632698","article-title":"Pretreatments for the efficient extraction of bioactive compounds from plant-based biomaterials","volume":"54","author":"Zhao","year":"2014","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_30","first-page":"1","article-title":"Extraction, isolation and characterization of bioactive compounds from plants\u2019 extracts","volume":"8","author":"Sasidharan","year":"2011","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jep.2014.03.051","article-title":"Bioactive compounds from Cornus officinalis fruits and their effects on diabetic nephropathy","volume":"153","author":"Ma","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nummenmaa, E., H\u00e4m\u00e4l\u00e4inen, M., Pemmari, A., Moilanen, L.J., Tuure, L., Nieminen, R.M., Moilanen, T., Vuolteenaho, K., and Moilanen, E. (2020). Transient receptor potential ankyrin 1 (TRPA1) is involved in upregulating interleukin-6 expression in osteoarthritic chondrocyte models. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010087"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S1063-4584(03)00168-7","article-title":"Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro","volume":"11","author":"Wang","year":"2003","journal-title":"Osteoarthr. Cartil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"202","DOI":"10.22203\/eCM.v021a16","article-title":"Roles of inflammatory and anabolic cytokines in cartilage metabolism: Signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis","volume":"21","author":"Goldring","year":"2011","journal-title":"Eur. Cells Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1016\/j.cellsig.2007.08.013","article-title":"MyD88, IRAK1 and TRAF6 knockdown in human chondrocytes inhibits interleukin-1-induced matrix metalloproteinase-13 gene expression and promoter activity by impairing MAP kinase activation","volume":"19","author":"Ahmad","year":"2007","journal-title":"Cell. Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"90","DOI":"10.6564\/JKMRS.2011.15.2.090","article-title":"1H NMR-based metabolomic study of Cornus officinalis from different geographical origin","volume":"15","author":"Jung","year":"2011","journal-title":"J. Korean Magn. Reson. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Czerwi\u0144ska, M.E., and Melzig, M.F. (2018). Cornus mas and Cornus officinalis\u2014Analogies and differences of two medicinal plants traditionally used. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00894"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Timur, U.T., Caron, M.M.J., Jeuken, R.M., Bastiaansen-Jenniskens, Y.M., Welting, T.J.M., van Rhijn, L.W., van Osch, G., and Emans, P.J. (2020). Chondroprotective actions of selective COX-2 inhibitors in vivo: A systematic review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186962"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/bph.13720","article-title":"Morroniside, a secoiridoid glycoside from Cornus officinalis, attenuates neuropathic pain by activation of spinal glucagon-like peptide-1 receptors","volume":"174","author":"Xu","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1248\/bpb.31.1422","article-title":"Protective effects of morroniside isolated from Corni fructus against renal damage in streptozotocin-induced diabetic rats","volume":"31","author":"Yokozawa","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pi, W.X., Feng, X.P., Ye, L.H., and Cai, B.C. (2017). Combination of morroniside and diosgenin prevents high glucose-induced cardiomyocytes apoptosis. Molecules, 22.","DOI":"10.3390\/molecules22010163"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.3892\/mmr.2017.6698","article-title":"Chlorogenic acid prevents inflammatory responses in IL-1\u03b2 stimulated human SW1353 chondrocytes, a model for osteoarthritis","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12872","DOI":"10.4238\/2015.October.21.7","article-title":"Differential expression of COX-2 in osteoarthritis and rheumatoid arthritis","volume":"14","author":"Fan","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.4049\/jimmunol.181.7.5082","article-title":"Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: Evidence for signaling via the EP4 receptor","volume":"181","author":"Attur","year":"2008","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7411","DOI":"10.1016\/j.biomaterials.2011.06.037","article-title":"The knee meniscus: Structure-function, pathophysiology, current repair techniques, and prospects for regeneration","volume":"32","author":"Makris","year":"2011","journal-title":"Biomaterials"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Choi, M.C., and Choi, W.H. (2018). Mithramycin A alleviates osteoarthritic cartilage destruction by inhibiting HIF-2\u03b1 expression. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051411"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/art.27290","article-title":"The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis","volume":"62","author":"Bondeson","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-4939-1619-1_12","article-title":"Mouse models of osteoarthritis: Surgical model of posttraumatic osteoarthritis induced by destabilization of the medial meniscus","volume":"1226","author":"Culley","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1002\/jor.23909","article-title":"Meniscal extrusion and degeneration during the course of osteoarthritis in the murine collagenase-induced osteoarthritis model","volume":"36","author":"Utomo","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Batiha, G.E., Olatunde, A., El-Mleeh, A., Hetta, H.F., Al-Rejaie, S., Alghamdi, S., Zahoor, M., Beshbishy, A.M., Murata, T., and Zaragoza-Bastida, A. (2020). Bioactive compounds, pharmacological actions, and pharmacokinetics of wormwood (Artemisia absinthium). Antibiotics, 9.","DOI":"10.3390\/antibiotics9060353"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1248\/cpb.57.112","article-title":"Iodine-catalyzed etherification of morroniside","volume":"57","author":"Sunghwa","year":"2009","journal-title":"Chem. Pharm. Bull."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Cho, C., Kang, L.J., Jang, D., Jeon, J., Lee, H., Choi, S., Han, S.J., Oh, E., Nam, J., and Kim, C.S. (2019). Cirsium japonicum var. maackii and apigenin block Hif-2\u03b1-induced osteoarthritic cartilage destruction. J. Cell. Mol. Med., 23.","DOI":"10.1111\/jcmm.14418"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/2987\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:36:03Z","timestamp":1760160963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/2987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22062987"],"URL":"https:\/\/doi.org\/10.3390\/ijms22062987","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,15]]}}}