{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:50:56Z","timestamp":1781304656312,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T00:00:00Z","timestamp":1445990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Honeybush tea, a sweet tasting caffeine-free tea that is indigenous to South Africa, is rich in bioactive compounds that may have beneficial health effects. Bone remodeling is a physiological process that involves the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. When resorption exceeds formation, bone remodeling can be disrupted resulting in bone diseases such as osteoporosis. Osteoclasts are multinucleated cells derived from hematopoietic precursors of monocytic lineage. These precursors fuse and differentiate into mature osteoclasts in the presence of receptor activator of NF-kB ligand (RANKL), produced by osteoblasts. In this study, the in vitro effects of an aqueous extract of fermented honeybush tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macrophages. We found that commercial honeybush tea extract inhibited osteoclast formation and TRAP activity which was accompanied by reduced bone resorption and disruption of characteristic cytoskeletal elements of mature osteoclasts without cytotoxicity. Furthermore, honeybush tea extract decreased expression of key osteoclast specific genes, matrix metalloproteinase-9 (MMP-9), tartrate resistant acid phosphatase (TRAP) and cathepsin K. This study demonstrates for the first time that honeybush tea may have potential anti-osteoclastogenic effects and therefore should be further explored for its beneficial effects on bone.<\/jats:p>","DOI":"10.3390\/ijerph121113779","type":"journal-article","created":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T13:43:01Z","timestamp":1446039781000},"page":"13779-13793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Commercial Honeybush (Cyclopia spp.) Tea Extract Inhibits Osteoclast Formation and Bone Resorption in RAW264.7 Murine Macrophages\u2014An in vitro Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Amcois","family":"Visagie","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001,  South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abe","family":"Kasonga","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001,  South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwa","family":"Deepak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001,  South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaakirah","family":"Moosa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001,  South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumari","family":"Marais","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001,  South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8646-9672","authenticated-orcid":false,"given":"Marlena","family":"Kruger","sequence":"additional","affiliation":[{"name":"School of Food and Nutrition, Massey Institute for Food Science and Technology, Massey University, Palmerston North 4442, New Zealand"},{"name":"Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa"},{"name":"Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-6044","authenticated-orcid":false,"given":"Magdalena","family":"Coetzee","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001,  South Africa"},{"name":"Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,10,28]]},"reference":[{"key":"ref_1","first-page":"164","article-title":"Recent update on osteoporosis","volume":"2","author":"Agrawal","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.abb.2008.03.037","article-title":"Osteoclast lineage and function","volume":"473","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1242\/jcs.113.3.377","article-title":"The cell biology of osteoclast function","volume":"113","author":"Zhao","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_4","first-page":"499","article-title":"Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption","volume":"52","author":"Halleen","year":"2006","journal-title":"Clin. Lab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/rheumatology\/kes259","article-title":"Osteoclast migration, differentiation and function: Novel therapeutic targets for rheumatic diseases","volume":"52","author":"Kikuta","year":"2013","journal-title":"Rheumatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/nrd916","article-title":"Discoveries, drugs and skeletal disorders","volume":"1","author":"Goltzman","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Takahashi, N., Udagawa, N., and Suda, T. (2014). Vitamin D endocrine system and osteoclasts. Bonekey Rep.","DOI":"10.1038\/bonekey.2013.229"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3803\/EnM.2010.25.4.264","article-title":"Molecular understanding of osteoclast differentiation and physiology","volume":"25","author":"Lee","year":"2010","journal-title":"Endocr. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.sajb.2011.05.014","article-title":"Honeybush (Cyclopia spp.): From local cottage industry to global markets\u2014The catalytic and supporting role of research","volume":"77","author":"Joubert","year":"2011","journal-title":"S. Afr. J. Bot."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ptr.1992","article-title":"A review of the bioactivity of South African herbal teas: Rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia)","volume":"21","author":"McKay","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.fitote.2008.11.001","article-title":"Honeybush (Cyclopia spp.)\u2014A rich source of compounds with high antimutagenic properties","volume":"80","author":"Kokotkiewicz","year":"2008","journal-title":"Fitoterapia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1383-5718(00)00128-5","article-title":"An investigation on the antimutagenic properties of South African herbal teas","volume":"471","author":"Marnewick","year":"2000","journal-title":"Mutat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.canlet.2004.11.014","article-title":"Inhibition of tumour promotion in mouse skin by extracts of Rooibos (Aspalathus linearis) and Honeybush (Cyclopia intermedia), unique South African herbal teas","volume":"224","author":"Marnewick","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.jnutbio.2010.05.007","article-title":"Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation","volume":"22","author":"Shen","year":"2011","journal-title":"J. Nutr. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s00198-007-0527-5","article-title":"Protective effect of green tea polyphenols on bone loss in middle-aged female rats","volume":"19","author":"Shen","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/15321811003617537","article-title":"The in vitro effects of Rooibos and black tea on immune pathways","volume":"31","author":"Hendricks","year":"2010","journal-title":"J. Immunoass. Immunochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jfca.2009.10.006","article-title":"Development of HPLC method for Cyclopia subternata phenolic compound analysis and application to other Cyclopia spp.","volume":"23","author":"Joubert","year":"2010","journal-title":"J. Food Compos. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3109\/03008207.2014.989320","article-title":"Inhibitory effects of eugenol on RANKL-induced osteoclast formation via attenuation of NF-kappaB and MAPK pathways","volume":"56","author":"Deepak","year":"2015","journal-title":"Connect. Tissue Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 Years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kasonga, A.E., Deepak, V., Kruger, M.C., and Coetzee, M. (2015). Arachidonic acid and docosahexaenoic acid suppress osteoclast formation and activity in human CD14+ monocytes, in vitro. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125145"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1002\/jcb.21553","article-title":"The osteoclast: A multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell","volume":"102","year":"2007","journal-title":"J. Cell Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nash, L.A., and Ward, W.E. (2015). Tea and bone health: Findings from human studies, potential mechanisms, and identification of knowledge gaps. Crit. Rev. Food Sci. Nutr.","DOI":"10.1080\/10408398.2014.1001019"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/ajcn\/86.4.1243","article-title":"Tea drinking is associated with benefits on bone density in older women","volume":"86","author":"Devine","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1001\/archinte.162.9.1001","article-title":"Epidemiological evidence of increased bone mineral density in habitual tea drinkers","volume":"162","author":"Wu","year":"2002","journal-title":"Arch. Intern. Med."},{"key":"ref_25","first-page":"57","article-title":"Relationship between tea drinking and bone mineral density in Iranian population","volume":"13","author":"Maghbooli","year":"2007","journal-title":"Iran. J. Public Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2190\/PM.44.1.f","article-title":"Factors associated with low bone density among women with major depressive disorder","volume":"44","author":"Hsiao","year":"2012","journal-title":"Int. J. Psychiat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/978-0-387-89520-8_9","article-title":"RANK(L) as a key target for controlling bone loss","volume":"647","author":"Leibbrandt","year":"2009","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/978-1-61779-415-5_13","article-title":"RANKL-mediated osteoclast formation from murine RAW 264.7 cells","volume":"816","author":"Osdoby","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.foodchem.2012.01.114","article-title":"Isolation and structure elucidation of phenolic compounds from Cyclopia subternata Vogel (Honeybush) intact plant and in vitro cultures","volume":"133","author":"Kokotkiewicz","year":"2012","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jfca.2015.08.002","article-title":"Honeybush herbal teas (Cyclopia spp.) contribute to high levels of dietary exposure to xanthones, benzophenones, dihydrochalcones and other bioactive phenolics","volume":"44","author":"Schulze","year":"2015","journal-title":"J. Food Compos. Anal."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/ptr.5001","article-title":"Hesperidin prevents androgen deficiency-induced bone loss in male mice","volume":"28","author":"Chiba","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1248\/bpb.21.1322","article-title":"The effect of Kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan","volume":"21","author":"Li","year":"1998","journal-title":"Biol. Pharm. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jcb.22800","article-title":"Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced activation of NF-kappaB and ERK","volume":"112","author":"Ang","year":"2011","journal-title":"J. Cell Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.phymed.2012.12.002","article-title":"Cyclopia maculata and Cyclopia subternata (honeybush tea) inhibits adipogenesis in 3T3-L1 pre-adipocytes","volume":"20","author":"Dudhia","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/jmicro\/52.6.551","article-title":"Cathepsins in the osteoclast","volume":"52","author":"Goto","year":"2003","journal-title":"J. Electron. Microsc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S8756-3282(00)00368-9","article-title":"Structure, function, and regulation of tartrate-resistant acid phosphatase","volume":"27","author":"Oddie","year":"2000","journal-title":"Bone"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/0-306-46826-3_32","article-title":"Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice","volume":"477","author":"Saftig","year":"2000","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1006\/excr.2002.5612","article-title":"Osteoclasts from mice deficient in tartrate-resistant acid phosphatase have altered ruffled borders and disturbed intracellular vesicular transport","volume":"279","author":"Hollberg","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.yexcr.2006.10.001","article-title":"RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation","volume":"313","author":"Sundaram","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/j.1600-0765.2004.00743.x","article-title":"Inhibitory effects of green tea polyphenol (\u2212)-epigallocatechin gallate on the expression of matrix metalloproteinase-9 and on the formation of osteoclasts","volume":"39","author":"Yun","year":"2004","journal-title":"J. Periodontal Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00776-007-1143-0","article-title":"Diet and lifestyle associated with increased bone mineral density: Cross-sectional study of Japanese elderly women at an osteoporosis outpatient clinic","volume":"12","author":"Muraki","year":"2007","journal-title":"J. Orthop. Sci."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/12\/11\/13779\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:51:03Z","timestamp":1760215863000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/12\/11\/13779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,28]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,11]]}},"alternative-id":["ijerph121113779"],"URL":"https:\/\/doi.org\/10.3390\/ijerph121113779","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,28]]}}}