{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:49Z","timestamp":1785403669337,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T00:00:00Z","timestamp":1675468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Osteoarthritis (OA) is a common disorder that can affect any joint in the human body. This study aimed to examine the anti-arthritic properties of high and low doses of grapefruit juice (GFJ), as grapefruit appears to contain anti-inflammatory biochemicals. Forty male Sprague\u2013Dawley rats weighing 170\u2013180 g were divided into five groups. These groups comprised the untreated control group and osteoarthritic (Osteo) rats administered intra-articular injections of Freund\u2019s complete adjuvant (CFA; 0.5 mL; 1 mg\/mL) as follows: OA rats administered low doses of GFJ (Osteo+GFJ (low); 5 mL\/kg body weight (BW)); OA rats administered high doses of GFJ (Osteo+GFJ (high); 27 mL\/kg BW); and OA rats administered diclofenac sodium (Osteo+Diclo) as a reference drug. Injections of CFA induced OA, as indicated by a significant increase in the serum levels of the inflammatory biomarkers C-reactive protein (CRP), interleukin-1\u03b2 (IL-1\u03b2), and (prostaglandin (PGE2), as well as matrix metalloproteinases (MMP-1) and cathepsin K. The synovial levels of glycosaminoglycans (GAGs), tumor necrosis factor (TNF-\u03b1), and interleukin 6 (IL-6) also increased, with a concomitant reduction in osteocalcin levels. The administration of either high or low doses of GFJ reduced CRP, IL-1\u03b2, PGE2, MMP-1, cathepsin K, and osteocalcin while increasing the synovial levels of GAGs, TNF-\u03b1, and IL-6, slowing cartilage degradation and boosting joint function. The results showed comparable histopathological and biochemical responses. A comparison of the treatments showed that high-dose GFJ had a greater chondroprotective effect than low-dose GFJ.<\/jats:p>","DOI":"10.3390\/nu15040798","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:59:10Z","timestamp":1675659550000},"page":"798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chondroprotective Effects of Grapefruit (Citrus paradisi Macfad.) Juice in a Complete Freund\u2019s Adjuvant Rat Model of Knee Osteoarthritis"],"prefix":"10.3390","volume":"15","author":[{"given":"Reem S.","family":"Alazragi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Science, University of Jeddah, P.O. Box 34, Jeddah 21959, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi M.","family":"Baeissa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, University of Jeddah, P.O. Box 34, Jeddah 21959, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115245","DOI":"10.1016\/j.bone.2020.115245","article-title":"Subchondral bone dysplasia partly participates in prenatal dexamethasone induced-osteoarthritis susceptibility in female offspring rats","volume":"133","author":"Xiao","year":"2020","journal-title":"Bone"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","article-title":"Proteases involved in cartilage matrix degradation in osteoarthritis","volume":"1824","author":"Troeberg","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/nrrheum.2016.148","article-title":"Changes in the osteochondral unit during osteoarthritis: Structure, function and cartilage\u2013bone crosstalk","volume":"12","author":"Goldring","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"118859","DOI":"10.1016\/j.ijpharm.2019.118859","article-title":"Thermoresponsive Hyalomer intra-articular hydrogels improve monoiodoacetate-induced osteoarthritis in rats","volume":"573","author":"Hanafy","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Coaccioli, S., Sarzi-Puttini, P., Zis, P., Rinonapoli, G., and Varrassi, G. (2022). Osteoarthritis: New insight on its pathophysiology. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206013"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Barreto, R.B., Santana, B.H.d., Martins, B.M., Porto, E.S., Severino, P., Cardoso, J.C., Souto, E.B., and Albuquerque-J\u00fanior, R.L.d. (2022). Application of Formononetin for the Treatment of Knee Osteoarthritis Induced by Medial Meniscectomy in a Rodent Model. Appl. Sci., 12.","DOI":"10.3390\/app12178591"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.drudis.2018.05.023","article-title":"Recent advances in intra-articular drug delivery systems for osteoarthritis therapy","volume":"23","author":"Maudens","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_8","first-page":"671","article-title":"Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex","volume":"19","author":"Abdulmajeed","year":"2015","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103306","DOI":"10.1016\/j.etap.2019.103306","article-title":"Allicin modulates diclofenac sodium induced hepatonephro toxicity in rats via reducing oxidative stress and caspase 3 protein expression","volume":"74","author":"Orabi","year":"2020","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.exger.2019.01.002","article-title":"Association between naturally occurring spine osteoarthritis in geriatric rats and neurogenic inflammation within neurosegmentally linked skeletal muscle","volume":"118","author":"Duarte","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_11","first-page":"129","article-title":"Hypoglycemic and hypolipidemic effects of grapefruit juice in diabetic rats","volume":"13","author":"Hamed","year":"2008","journal-title":"Tikrit J. Pure Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Stabrauskiene, J., Kopustinskiene, D.M., Lazauskas, R., and Bernatoniene, J. (2022). Naringin and naringenin: Their mechanisms of action and the potential anticancer activities. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071686"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chudnovskiy, R., Thompson, A., Tharp, K., Hellerstein, M., Napoli, J.L., and Stahl, A. (2014). Consumption of clarified grapefruit juice ameliorates high-fat diet induced insulin resistance and weight gain in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108408"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1002\/art.24817","article-title":"Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment","volume":"60","author":"Ochaion","year":"2009","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Levy, A.S., Simon, O., Shelly, J., and Gardener, M. (2006). 6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund\u2019s adjuvant. BMC Pharmacol., 6.","DOI":"10.1186\/1471-2210-6-12"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S380","DOI":"10.1016\/S0924-8579(07)71209-8","article-title":"P1369 Modification of cephalexin serum concentration by grapefruit juice co-administration in rats","volume":"29","author":"Cuciureanu","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S2221-1691(13)60116-1","article-title":"Ameliorative effect of grapefruit juice on amiodarone\u2013induced cytogenetic and testicular damage in albino rats","volume":"3","author":"Sakr","year":"2013","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3329\/jbsp.v10i1.24615","article-title":"Antinociceptive and Anti-inflammatory Effects of Combined Administration of a-tocopherol and Diclofenac","volume":"10","author":"Juaira","year":"2015","journal-title":"J. Bangladesh Soc. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1136\/ard.55.10.695","article-title":"Microscopic analysis of synovial fluid--the perfect diagnostic test?","volume":"55","author":"Freemont","year":"1996","journal-title":"Ann. Rheum. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/j.jsps.2022.10.008","article-title":"Noscapine hydrochloride (benzyl-isoquinoline alkaloid) effectively prevents protein denaturation through reduction of IL-6, NF-kB, COX-2, Prostaglandin-E2 in rheumatic rats","volume":"30","author":"Akhter","year":"2022","journal-title":"Saudi Pharm. J."},{"key":"ref_21","first-page":"19476035221102566","article-title":"Decrease in Glycosaminoglycan with Aging in Normal Rat Articular Cartilage Is Greater in Females than in Males","volume":"13","author":"Osago","year":"2022","journal-title":"Cartilage"},{"key":"ref_22","unstructured":"Suvarna, K.S., Layton, C., and Bancroft, J.D. (2018). Bancroft\u2019s Theory and Practice of Histological Techniques E-Book, Elsevier Health Sciences."},{"key":"ref_23","first-page":"062","article-title":"Is there crosstalk between subchondral bone, cartilage, and meniscus in the pathogenesis of osteoarthritis?","volume":"27","author":"Atik","year":"2016","journal-title":"Jt. Dis. Relat. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16028","DOI":"10.1038\/boneres.2016.28","article-title":"Bone\u2013cartilage crosstalk: A conversation for understanding osteoarthritis","volume":"4","author":"Findlay","year":"2016","journal-title":"Bone Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1007\/s10753-012-9444-7","article-title":"Effect of ethanol extract of Trigonella foenum graecum (Fenugreek) seeds on Freund\u2019s adjuvant-induced arthritis in albino rats","volume":"35","author":"Suresh","year":"2012","journal-title":"Inflammation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"113602","DOI":"10.1016\/j.jep.2020.113602","article-title":"Tunisian Olea europaea L. leaf extract suppresses Freund\u2019s complete adjuvant-induced rheumatoid arthritis and lipopolysaccharide-induced inflammatory responses","volume":"268","author":"Hong","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2217\/ijr.13.5","article-title":"Diclofenac in the treatment of osteoarthritis","volume":"8","author":"Roth","year":"2013","journal-title":"Int. J. Clin. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1136\/gutjnl-2017-314786","article-title":"Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial","volume":"68","author":"Roager","year":"2019","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0031-6865(99)00062-X","article-title":"Content of CYP3A4 inhibitors, naringin, naringenin and bergapten in grapefruit and grapefruit juice products","volume":"74","author":"Ho","year":"2000","journal-title":"Pharm. Acta Helv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/open.202100223","article-title":"Flavonoids in lemon and grapefruit IntegroPectin","volume":"10","author":"Scurria","year":"2021","journal-title":"ChemistryOpen"},{"key":"ref_31","unstructured":"Bacanl\u0131, M., Ba\u015faran, A.A., and Ba\u015faran, N. (2018). Polyphenols: Prevention and Treatment of Human Disease, Elsevier."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.3748\/wjg.v23.i28.5097","article-title":"Therapeutic potential of flavonoids in inflammatory bowel disease: A comprehensive review","volume":"23","author":"Salaritabar","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3390\/nu5030637","article-title":"Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats","volume":"5","author":"Alam","year":"2013","journal-title":"Nutrients"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.metabol.2011.12.004","article-title":"The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults","volume":"61","author":"Dow","year":"2012","journal-title":"Metabolism"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jfda.2014.06.005","article-title":"Hypocholesterolemic properties of grapefruit (Citrus paradisii) and shaddock (Citrus maxima) juices and inhibition of angiotensin-1-converting enzyme activity","volume":"22","author":"Oboh","year":"2014","journal-title":"J. Food Drug Anal."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.joca.2019.06.014","article-title":"Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced-patellofemoral joint osteoarthritis","volume":"28","author":"Bei","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jgr.2020.01.004","article-title":"Ginsenoside Rb1 inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation","volume":"45","author":"Aravinthan","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15226\/2475-4676\/2\/4\/00129","article-title":"Formulation and Evaluation of Novel Herbal Aerosol for Arthritis","volume":"2","author":"Aiyalu","year":"2017","journal-title":"J. Rheumatol. Arthritic Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, J. (2018). Meta-analysis of serum C-reactive protein and cartilage oligomeric matrix protein levels as biomarkers for clinical knee osteoarthritis. BMC Musculoskelet. Disord., 19.","DOI":"10.1186\/s12891-018-1932-y"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.joca.2008.01.014","article-title":"Should subchondral bone turnover be targeted when treating osteoarthritis?","volume":"16","author":"Karsdal","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbacli.2016.05.002","article-title":"Glycosaminoglycan measured from synovial fluid serves as a useful indicator for progression of Osteoarthritis and complements Kellgren\u2013Lawrence Score","volume":"6","author":"Kulkarni","year":"2016","journal-title":"BBA Clin."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nirmal, P.S., Jagtap, S.D., Narkhede, A.N., Nagarkar, B.E., and Harsulkar, A.M. (2017). New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-016-1535-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1089\/jmf.2014.0088","article-title":"Helichrysum and grapefruit extracts boost weight loss in overweight rats reducing inflammation","volume":"18","author":"Etxeberria","year":"2015","journal-title":"J. Med. Food"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.lfs.2018.07.017","article-title":"Combating oxidative stress disorders with citrus flavonoid: Naringenin","volume":"208","author":"Zaidun","year":"2018","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1021\/acs.molpharmaceut.7b00797","article-title":"Grapefruit flavonoid Naringenin regulates the expression of LXR\u03b1 in THP-1 macrophages by modulating AMP-activated protein kinase","volume":"15","author":"Saenz","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jdermsci.2015.12.008","article-title":"Naringin protects ultraviolet B-induced skin damage by regulating p38 MAPK signal pathway","volume":"82","author":"Ren","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_48","first-page":"3746","article-title":"Effect of naringin on monosodium iodoacetate-induced osteoarthritis pain in rats","volume":"23","author":"Xu","year":"2017","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Souza, J.M., Tuin, S.A., Robinson, A.G., Souza, J.G.O., Bianchini, M.A., and Miguez, P.A. (2020). Effect of Flavonoid Supplementation on Alveolar Bone Healing-A Randomized Pilot Trial. Dent. J., 8.","DOI":"10.3390\/dj8030086"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.fct.2017.12.038","article-title":"Grapefruit and its biomedical, antigenotoxic and chemopreventive properties","volume":"112","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.bbrc.2012.12.003","article-title":"Hyaluronan inhibits TLR-4 dependent cathepsin K and matrix metalloproteinase 1 expression in human fibroblasts","volume":"430","author":"Hirabara","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"102183","DOI":"10.1016\/j.ctim.2019.08.017","article-title":"The efficacy of topical sesame oil in patients with knee osteoarthritis: A randomized double-blinded active-controlled non-inferiority clinical trial","volume":"47","author":"Askari","year":"2019","journal-title":"Complement. Ther. Med."},{"key":"ref_53","first-page":"E193","article-title":"Osteocalcin in serum, saliva and gingival crevicular fluid: Their relation with periodontal treatment outcome in postmenopausal women","volume":"12","author":"Bullon","year":"2007","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.nut.2005.12.002","article-title":"Citrus juice modulates bone strength in male senescent rat model of osteoporosis","volume":"22","author":"Deyhim","year":"2006","journal-title":"Nutrition"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1093\/jn\/133.6.1892","article-title":"Hesperidin, a Citrus Flavonoid, Inhibits Bone Loss and Decreases Serum and Hepatic Lipids in Ovariectomized Mice","volume":"133","author":"Chiba","year":"2003","journal-title":"J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1021\/jf0484632","article-title":"Antioxidant Activity of Citrus Limonoids, Flavonoids, and Coumarins","volume":"53","author":"Yu","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s00776-013-0362-9","article-title":"Naringin promotes osteoblast differentiation and effectively reverses ovariectomy-associated osteoporosis","volume":"18","author":"Xu","year":"2013","journal-title":"J. Orthop. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e5714","DOI":"10.1590\/1414-431x20165714","article-title":"Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model","volume":"50","author":"Wang","year":"2017","journal-title":"Braz. J. Med. Biol. Res. = Rev. Bras. Pesqui. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153134","DOI":"10.1016\/j.phymed.2019.153134","article-title":"Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflammation and rheumatoid arthritis","volume":"66","author":"Hasan","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1007\/s11926-012-0288-9","article-title":"Intersection of inflammation and herbal medicine in the treatment of osteoarthritis","volume":"14","author":"Mobasheri","year":"2012","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/j.joca.2019.08.007","article-title":"Intra-articular injection of magnesium chloride attenuates osteoarthritis progression in rats","volume":"27","author":"Yao","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"730907","DOI":"10.1155\/2012\/730907","article-title":"Effect of GCSB-5, a Herbal Formulation, on Monosodium Iodoacetate-Induced Osteoarthritis in Rats","volume":"2012","author":"Kim","year":"2012","journal-title":"Evid. -Based Complement. Altern. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kim, Y., Park, H.-J., Kim, M.-K., Kim, Y.-I., Kim, H.J., Bae, S.-K., N\u00f6r, J.E., and Bae, M.-K. (J. Dent. Sci., 2022). Naringenin stimulates osteogenic\/odontogenic differentiation and migration of human dental pulp stem cells, J. Dent. Sci., in press.","DOI":"10.1016\/j.jds.2022.08.029"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.joca.2015.05.035","article-title":"Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy","volume":"23","author":"Larsson","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109347","DOI":"10.1016\/j.biopha.2019.109347","article-title":"Anti-inflammatory effect and potential mechanism of betulinic acid on \u03bb-carrageenan-induced paw edema in mice","volume":"118","author":"Ou","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Aborehab, N.M., El Bishbishy, M.H., Refaiy, A., and Waly, N.E. (2017). A putative Chondroprotective role for IL-1\u03b2 and MPO in herbal treatment of experimental osteoarthritis. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-2002-y"},{"key":"ref_67","first-page":"1","article-title":"Naringin in the repair of knee cartilage injury via the TGF-\u03b2\/ALK5\/Smad2\/3 signal transduction pathway combined with an acellular dermal matrix","volume":"32","author":"Ye","year":"2022","journal-title":"J. Orthop. Transl."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.1038\/s41598-019-42546-7","article-title":"Knee osteoarthritis induces atrophy and neuromuscular junction remodeling in the quadriceps and tibialis anterior muscles of rats","volume":"9","author":"Cunha","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.etap.2018.05.009","article-title":"Diabetes escalates knee osteoarthritis in rats: Evidence of adaptive mechanism","volume":"61","author":"Adeyemi","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/4\/798\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:24:02Z","timestamp":1760120642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/4\/798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,4]]},"references-count":69,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["nu15040798"],"URL":"https:\/\/doi.org\/10.3390\/nu15040798","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,4]]}}}