{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:51:15Z","timestamp":1770414675345,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"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>The aim of this study was to investigate the chondroprotective effect of a standardized extract (KBH-JP-040) of the Korean traditional herbs Kalopanax pictus Castor-Aralia, Hericium erinaceus (Bull.) Persoon, and Astragalus membranaceus Schischkin on in vivo and in vitro osteoarthritis (OA) models. Cultured rat chondrocytes were pre-treated with KBH-JP-040 (50, 100 and 200 \u03bcg\/mL) for 1 h, then recombinant human IL-1\u03b1 (rhIL-1\u03b1) for 24 h. For the in vivo model, rabbits (n = 60) were equally divided into experimental groups: normal control (NC), a collagenase-induced OA group, and OA groups treated with KBH-JP-040 (75, 100, and 150 mg\/kg body weight) and celecoxib (Cx, 100 mg\/kg) orally for 28 days. Treatment with KBH-JP-040 significantly attenuated inflammatory cytokines and matrix metalloproteinases (MMPs), suppressed the expression of I\u03baB\u03b1, NF-\u03baB, and JNK\/p38 mitogen-activated protein (MAP) kinase, and upregulated aggrecan and collagen type-II expression in rhIL-1\u03b1-stimulated chondrocytes. Furthermore, the serum and synovial levels of inflammatory cytokines of rabbits also decreased in the treatment groups when compared with the OA group. Improved magnetic resonance imaging and histopathological findings further confirmed the therapeutic efficacy of KBH-JP-040 against OA. In conclusion, these results indicate that KBH-JP-040 possesses chondroprotective effects, suppressing inflammation and MMPs, and downregulating I\u03baB\u03b1, NF-\u03baB, and JNK\/p38 MAP kinase-signaling pathways. This might be a potential therapeutic candidate for OA treatment.<\/jats:p>","DOI":"10.3390\/nu10030356","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T16:07:17Z","timestamp":1521130037000},"page":"356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chondroprotective Effects of a Standardized Extract (KBH-JP-040) from Kalopanax pictus, Hericium erinaceus, and Astragalus membranaceus in Experimentally Induced In Vitro and In Vivo Osteoarthritis Models"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0243-7746","authenticated-orcid":false,"given":"Md.","family":"Rahman","sequence":"first","affiliation":[{"name":"KNOTUS Co., Ltd. Research and Development Center, 189 Donggureung-Ro, Guri-Si 11910, Gyeonggi-Do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Kolmar BNH Co., Ltd. 22-15, Sandan-gil, Jeonui-myeon, Sejong-si 30003, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Kolmar BNH Co., Ltd. 22-15, Sandan-gil, Jeonui-myeon, Sejong-si 30003, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myung-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"KNOTUS Co., Ltd. Research and Development Center, 189 Donggureung-Ro, Guri-Si 11910, Gyeonggi-Do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do-Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"KNOTUS Co., Ltd. Research and Development Center, 189 Donggureung-Ro, Guri-Si 11910, Gyeonggi-Do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-7173","authenticated-orcid":false,"given":"Hak","family":"Lee","sequence":"additional","affiliation":[{"name":"Kolmar BNH Co., Ltd. 22-15, Sandan-gil, Jeonui-myeon, Sejong-si 30003, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1136\/pmj.79.933.377","article-title":"Osteoarthritis","volume":"79","author":"Haq","year":"2003","journal-title":"J. Postgrad. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jep.2009.07.010","article-title":"Therapeutic effect of Aralia cordata extracts on cartilage protection in collagenase-induced inflammatory arthritis rabbit model","volume":"125","author":"Park","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1142\/S0192415X13500948","article-title":"Influence of six medicinal herbs on collagenase-induced osteoarthritis in rats","volume":"41","author":"Nirmal","year":"2013","journal-title":"Am. J. Chin. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nrrheum.2015.135","article-title":"Strategies for the prevention of knee osteoarthritis","volume":"12","author":"Roos","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.semarthrit.2005.01.013","article-title":"Osteoarthritis: An overview of the disease and its treatment strategies","volume":"35","author":"Cimmino","year":"2005","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1007\/s11999-015-4450-3","article-title":"Prevalence and risk factors of spine, shoulder, hand, hip, and knee osteoarthritis in community-dwelling Koreans older than age 65 years","volume":"473","author":"Cho","year":"2015","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1002\/acr.23211","article-title":"Bone mineral density and the risk of hip and knee osteoarthritis: The Johnston county osteoarthritis project","volume":"69","author":"Barbour","year":"2017","journal-title":"Arthritis Care Res."},{"key":"ref_8","first-page":"w13583","article-title":"Biomechanics and pathomechanisms of osteoarthritis","volume":"142","author":"Egloff","year":"2012","journal-title":"Swiss Med. Wkly."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e222","DOI":"10.1111\/sms.12290","article-title":"Physical activity ameliorates cartilage degeneration in a rat model of aging: A study on lubricin expression","volume":"25","author":"Musumeci","year":"2015","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1254\/jphs.08010FP","article-title":"Therapeutic effect of siegesbeckia pubescens on cartilage protection in a rabbit collagenase-induced model of osteoarthritis","volume":"107","author":"Huh","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_11","first-page":"437","article-title":"Cardiovascular risk associated with celecoxib or etoricoxib: A meta-analysis of randomized controlled trials which adopted comparison with placebo or naproxen","volume":"62","author":"Baldi","year":"2014","journal-title":"Minerva Cardioangiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1016\/j.jnutbio.2013.07.007","article-title":"Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: An in vivo and in vitro study on lubricin expression","volume":"24","author":"Musumeci","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0378-8741(01)00382-8","article-title":"Kalopanaxsaponin a from Kalopanax pictus, a potent antioxidant in the rheumatoidal rat treated with freund\u2019s complete adjuvant reagent","volume":"79","author":"Choi","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jep.2004.05.015","article-title":"Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax pictus, pueraria thunbergiana and rhus verniciflua","volume":"94","author":"Kim","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chang, H.C., Yang, H.L., Pan, J.H., Korivi, M., Pan, J.Y., Hsieh, M.C., Chao, P.M., Huang, P.J., Tsai, C.T., and Hseu, Y.C. (2016). Hericium erinaceus inhibits tnf-alpha-induced angiogenesis and ros generation through suppression of mmp-9\/nf-kappab signaling and activation of nrf2-mediated antioxidant genes in human ea.Hy926 endothelial cells. Oxid. Med. Cell. Longev., 8257238.","DOI":"10.1155\/2016\/8257238"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.4062\/biomolther.2014.103","article-title":"Protective effect of liriodendrin isolated from Kalopanax pictus against gastric injury","volume":"23","author":"Sohn","year":"2015","journal-title":"Biomol. Ther."},{"key":"ref_17","first-page":"613","article-title":"The pharmacology and clinical properties of Kalopanax pictus","volume":"3","author":"Hyun","year":"2009","journal-title":"J. Med. Plants Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.4062\/biomolther.2013.069","article-title":"Kalopanaxsaponin an exerts anti-inflammatory effects in lipopolysaccharide-stimulated microglia via inhibition of jnk and nf-kappab\/ap-1 pathways","volume":"21","author":"Jeong","year":"2013","journal-title":"Biomol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1002\/ptr.5188","article-title":"Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (huangqi)","volume":"28","author":"Fu","year":"2014","journal-title":"Phytother. Res. PTR"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.2147\/DDDT.S114022","article-title":"Formononetin, an active compound of Astragalus membranaceus (fisch) bunge, inhibits hypoxia-induced retinal neovascularization via the hif-1alpha\/vegf signaling pathway","volume":"10","author":"Wu","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.1021\/acs.jafc.5b02914","article-title":"Chemistry, nutrition, and health-promoting properties of Hericium erinaceus (lion\u2019s mane) mushroom fruiting bodies and mycelia and their bioactive compounds","volume":"63","author":"Friedman","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1016\/j.bmcl.2015.10.016","article-title":"Chemical constituents from Hericium erinaceus and their ability to stimulate ngf-mediated neurite outgrowth on pc12 cells","volume":"25","author":"Zhang","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/jor.22671","article-title":"Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors","volume":"32","author":"Matuska","year":"2014","journal-title":"J. Orthop. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/jn\/132.3.341","article-title":"Catechins from green tea (camellia sinensis) inhibit bovine and human cartilage proteoglycan and type\u2161 collagen degradation in vitro","volume":"132","author":"Adcocks","year":"2002","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.joca.2008.06.017","article-title":"Use of routine clinical multimodality imaging in a rabbit model of osteoarthritis\u2014Part I","volume":"17","author":"Bouchgua","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/art.1780260709","article-title":"A new model of osteoarthritis in rabbits. I. Development of knee joint pathology following lateral meniscectomy and section of the fibular collateral and sesamoid ligaments","volume":"26","author":"Colombo","year":"1983","journal-title":"Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3892\/etm.2013.1074","article-title":"Antioxidant and anti-inflammatory effects of astragalus polysaccharide on ea.Hy926 cells","volume":"6","author":"Huang","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s10753-016-0416-1","article-title":"Protective role of liriodendrin in sepsis-induced acute lung injury","volume":"39","author":"Yang","year":"2016","journal-title":"Inflammation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1021\/acs.jnatprod.5b00709","article-title":"Betulin derivatives effectively suppress inflammation in vitro and in vivo","volume":"79","author":"Laavola","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2798","DOI":"10.1038\/cddis.2017.39","article-title":"Betulin exhibits anti-inflammatory activity in lps-stimulated macrophages and endotoxin-shocked mice through an ampk\/akt\/nrf2-dependent mechanism","volume":"8","author":"Ci","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1007\/s10753-013-9700-5","article-title":"Formononetin inhibited the inflammation of lps-induced acute lung injury in mice associated with induction of ppar gamma expression","volume":"36","author":"Ma","year":"2013","journal-title":"Inflammation"},{"key":"ref_32","first-page":"6201","article-title":"Formononetin ameliorates mast cell-mediated allergic inflammation via inhibition of histamine release and production of pro-inflammatory cytokines","volume":"14","author":"Xu","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"561459","DOI":"10.1155\/2014\/561459","article-title":"The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis","volume":"2014","author":"Wojdasiewicz","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.intimp.2010.09.021","article-title":"Anti-arthritic effects of chlorogenic acid in interleukin-1beta-induced rabbit chondrocytes and a rabbit osteoarthritis model","volume":"11","author":"Chen","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/ptr.5002","article-title":"Anti-inflammatory activities of an active fraction isolated from the root of Astragalus membranaceus in raw 264.7 macrophages","volume":"28","author":"Lai","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3109\/08923973.2011.633527","article-title":"Hericium erinaceus suppresses lps-induced pro-inflammation gene activation in raw264.7 macrophages","volume":"34","author":"Kim","year":"2012","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1248\/bpb.25.472","article-title":"In vitro antiinflammatory activity of kalopanaxsaponin an isolated from Kalopanax pictus in murine macrophage raw 264.7 cells","volume":"25","author":"Kim","year":"2002","journal-title":"Biol. Pharm. Bull."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jep.2010.12.005","article-title":"Effect of phellodendron amurense in protecting human osteoarthritic cartilage and chondrocytes","volume":"134","author":"Kim","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00011-012-0546-3","article-title":"Anti-arthritic effects of crocin in interleukin-1beta-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model","volume":"62","author":"Ding","year":"2013","journal-title":"Inflamm. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1021\/np200382s","article-title":"Anti-inflammatory triterpenoid saponins from the stem bark of Kalopanax pictus","volume":"74","author":"Quang","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3839\/jksabc.2009.064","article-title":"Antioxidant and anti-inflammatory activity of Kalopanax pictus leaf","volume":"52","author":"Hu","year":"2009","journal-title":"J. Korean Soc. Appl. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jep.2009.08.046","article-title":"Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models","volume":"126","author":"Zhang","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1532-950X.2007.00363.x","article-title":"Osteophytosis, subchondral bone sclerosis, joint effusion and soft tissue thickening in canine experimental stifle osteoarthritis: Comparison between 1.5 t magnetic resonance imaging and computed radiography","volume":"37","author":"Moreau","year":"2008","journal-title":"Vet. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Jia, L., Chen, J., Wang, Y., Liu, Y., Zhang, Y., and Chen, W. (2014). Magnetic resonance imaging of osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis rabbit model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113707"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/3\/356\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:17Z","timestamp":1760194637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/3\/356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["nu10030356"],"URL":"https:\/\/doi.org\/10.3390\/nu10030356","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,15]]}}}