{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:04:51Z","timestamp":1753887891446,"version":"3.41.2"},"reference-count":40,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Braz. Dent. J."],"abstract":"<jats:p>Abstract Periodontitis is a common chronic inflammatory disease characterized by alveolar bone loss. The high polyphenol content in cocoa pod husk (Theobroma cacao L) has the potential to influence bone metabolism and contribute to the inhibition of bone resorption. The aim of this study was to analyze the anti-osteoclastogenesis potential of cocoa pod husk (Theobroma cacao L.) in both in silico and in vivo study. An analysis of the anti-osteoclastogenesis potential of T. cacao bioactive compounds was conducted using molecular docking simulations. Thirty male Wistar rats (Rattus novergicus) were randomly assigned to control negative groups (placebo gel), control positive groups (2% doxycycline gel), and treatment groups (10% cocoa pod husk (CPH) extract gel), with measurements taken on days 7 and 14. Wistar rats were induced with 0.05 ml of P. gingivalis at a concentration of 2x109 CFU\/ml intrasulcularly in the maxillary molar to achieved in periodontitis. The number of osteoclasts was observed by hematoxylin and eosin staining, the level of TNF-\u03b1 was assessed by enzyme-linked immunosorbent assay, and the expression of RANKL was evaluated by immunohistochemical staining. Data were analyzed using One-way ANOVA to examine the differences between the groups. The in silico study showed that the catechin, epicatechin, quercetin, and procyanidin B2 had a strong binding affinity for TNF-\u03b1 and RANKL. Administration of 10% CPH reduced the number of osteoclasts (p&lt;0.05), TNF-\u03b1 level on days 7 and 14 (p&lt;0.05), and RANKL expression on day 7 (p&lt;0.05) in experimental rats with periodontitis. Administering 10% CPH inhibited osteoclastogenesis in the experimental periodontitis rats.<\/jats:p>","DOI":"10.1590\/0103-6440202406015","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T12:35:53Z","timestamp":1733142953000},"source":"Crossref","is-referenced-by-count":0,"title":["Anti-Osteoclastogenesis Potential of Cocoa Pod Husk (Theobroma cacao L.) Extract: In Silico and In Vivo Study"],"prefix":"10.1590","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9915-0468","authenticated-orcid":false,"given":"Yani Corvianindya","family":"Rahayu","sequence":"first","affiliation":[{"name":"Universitas Airlangga,  Indonesia; Universitas Jember,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-974X","authenticated-orcid":false,"given":"Ernie Maduratna","family":"Setiawatie","sequence":"additional","affiliation":[{"name":"Universitas Airlangga,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-3653","authenticated-orcid":false,"given":"Retno Pudji","family":"Rahayu","sequence":"additional","affiliation":[{"name":"Universitas Airlangga,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-8929","authenticated-orcid":false,"given":"S","family":"Siswandono","sequence":"additional","affiliation":[{"name":"Universitas Airlangga,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-6782","authenticated-orcid":false,"given":"Retno","family":"Indrawati","sequence":"additional","affiliation":[{"name":"Universitas Airlangga,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-3372","authenticated-orcid":false,"given":"Hendrik Setia","family":"Budi","sequence":"additional","affiliation":[{"name":"Universitas Airlangga,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3905-7413","authenticated-orcid":false,"given":"Hari Basuki","family":"Notobroto","sequence":"additional","affiliation":[{"name":"Universitas Airlangga,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8539-3687","authenticated-orcid":false,"given":"Rahmah A. Alwasilah","family":"Darojah","sequence":"additional","affiliation":[{"name":"Universitas Jember,  Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","published-online":{"date-parts":[[2024]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3390\/bioengineering10111274","article-title":"Ageing and Inflammation: What happens in Periodontium?","volume":"10","author":"Zhu L","year":"2023","journal-title":"Bioengineering"},{"issue":"1","key":"ref2","first-page":"59","article-title":"Ozon therapy in periodontic","volume":"5","author":"Bansal G","year":"2022","journal-title":"J Med Life"},{"issue":"3","key":"ref3","article-title":"Your health is in your mouth: A comprehensive view to promote general wellness","volume":"14","author":"Barranca-E.A Romo-Gonz\u00e1lez T","year":"2022","journal-title":"Front Oral Health"},{"issue":"2","key":"ref4","first-page":"239","article-title":"Effect of severity of chronic periodontitis on oral health-related quality of life","volume":"16","author":"Salari A","year":"2023","journal-title":"Maedica"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41368-019-0068-8","article-title":"Interleukin-1\u03b2 is a potential therapeutic target for periodontitis: a narrative review","volume":"12","author":"Cheng R","year":"2020","journal-title":"Int J Oral Sci"},{"issue":"10","key":"ref6","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.3390\/ijms23105540","article-title":"Osteoimmunology in periodontitis: local proteins and compounds to alleviate periodontitis","volume":"23","author":"Sirisereephap K","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"8","key":"ref7","first-page":"373","article-title":"Effectiveness of cassava leaves extract (Manihot esculenta rantz) on the number of osteoblast and osteoclast of periodontitis rat model","volume":"6","author":"Shita ADP","year":"2022","journal-title":"Health Notion"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"342","DOI":"10.4103\/ccd.ccd_97_18","article-title":"Comparative evaluation of serum tumor necrosis factor \u03b1 in health and chronic periodontitis: a Case-control study","volume":"11","author":"Jain P","year":"2020","journal-title":"Contemp Clin Dent"},{"key":"ref9","article-title":"Identification of potential TNF-\u03b1 inhibitors: from in silico to in vitro studies","volume":"10","author":"Zia K","year":"2020","journal-title":"Sci Rep"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1152\/physrev.00036.2016","article-title":"Osteoimmunology: The conceptual framework unifying the immune and skeletal systems","volume":"97","author":"Okamoto K","year":"2017","journal-title":"Physiol Rev"},{"issue":"7","key":"ref11","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1902\/jop.2007.070073","article-title":"RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis","volume":"78","author":"Jin Q","year":"2007","journal-title":"J Periodontol"},{"key":"ref12","first-page":"1","article-title":"Inflammasomes in Alveolar Bone Loss","volume":"12","author":"Li Y","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1186\/s12903-023-03241-2","article-title":"Effectiveness of chlorhexidine gels and chips in periodontitis patients after scaling and root planing: a systematic review and meta-analysis","volume":"23","author":"Annisa ZU Sulijaya B","year":"2023","journal-title":"BMC Oral Health"},{"issue":"5","key":"ref14","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3390\/molecules21050559","article-title":"The traditional medicine and modern medicine from natural products","volume":"21","author":"Yuan H","year":"2016","journal-title":"Molecules"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2329-6836.1000308","article-title":"Comparison of medicinally important natural products versus synthetic drugs-a short commentary","volume":"6","author":"Nisar B","year":"2018","journal-title":"Nat Prod Chem Res"},{"issue":"2","key":"ref16","first-page":"14","article-title":"Study of benefits of active compounds in cacao pod rind extract (Theobroma cacao)","volume":"15","author":"Sukatik Yetri Y","year":"2020","journal-title":"J Ilmiah Poli Rekayasa"},{"issue":"4","key":"ref17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.20473\/j.djmkg.v56.i4.p220-225","article-title":"Analysis of antioxidant and antibacterial activity of cocoa pod husk extract (Theobroma cacao L.)","volume":"56","author":"Rahayu YC","year":"2023","journal-title":"Dent J"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.30659\/odj.9.1.46-52","article-title":"The cytotoxic and proliferative activity of cocoa pod husk extract (Theobroma cacao L.) on periodontal ligament fibroblasts","volume":"9","author":"Rahayu YC","year":"2022","journal-title":"Odonto Dent J"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.30649\/denta.v14i2.6","article-title":"The Effect of proanthocyanidin cocoa pod rind extract (Theobroma cacao L.) on MMP-8 expession in gingival tissue of periodontitis rats model","volume":"14","author":"Rahayu YC","year":"2021","journal-title":"Denta Jurnal"},{"issue":"3","key":"ref20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/dj8030086","article-title":"Effect of flavonoid supplementation on alveolar bone healing-a randomized pilot trial","volume":"8","author":"Souza JM","year":"2020","journal-title":"Dent J"},{"issue":"2","key":"ref21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.5114\/bta.2023.127206","article-title":"Computational evaluation of bioactive compounds in Curcuma zanthorrhiza targeting SIRT1 and NF\u03baB","volume":"104","author":"Prasetyawan S","year":"2023","journal-title":"BioTechnologia"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"6535","DOI":"10.48048\/tis.2023.6535","article-title":"Effects of cocoa pod husk extract (Theobroma cacao L.) on alveolar bone in experimental","volume":"20","author":"Rahayu YC","year":"2023","journal-title":"Trends In Sci"},{"issue":"16","key":"ref23","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"177","author":"Percie du Sert N","year":"2020","journal-title":"Br J Pharmacoln"},{"issue":"6","key":"ref24","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1002\/vms3.936","article-title":"Optimisation of ketamine-xylazine anaesthetic dose and its association with changes in the dendritic spine of CA1 hippocampus in the young and old male and female Wistar rats","volume":"8","author":"Sotoudeh N","year":"2022","journal-title":"Vet Med Sci"},{"key":"ref25","first-page":"1093 012037","article-title":"Effectivity of black tea polyphenol in adipogenesis-related IGF-1 and its receptor pathway through in silico based study","author":"Susanto H","year":"2018","journal-title":"J Phys: Conf Ser"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.20473\/j.djmkg.v45.i2.p102-106","article-title":"Deoxypyridinoline level in gingival crevicular fluid as alveolar bone loss biomarker in periodontal disease","volume":"45","author":"Dharmayanti A.W.S","year":"2012","journal-title":"Dent J"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s11101-017-9529-x","article-title":"Molecular signaling mechanisms behind polyphenol-induced bone anabolism","volume":"16","author":"Torre E","year":"2017","journal-title":"Phytochem Rev"},{"key":"ref28","article-title":"Polyphenols as potential preventers of osteoporosis: A comprehensive review on antioxidant and anti-inflammatory effects, molecular mechanisms, and signal pathways in bone metabolism","volume":"123","author":"Zhan S","year":"2024","journal-title":"J Nutr Biochem"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s10753-020-01188-y","article-title":"Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model","volume":"43","author":"Patel A","year":"2020","journal-title":"Inflammation"},{"issue":"3","key":"ref30","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/idj.12221","article-title":"Non-antibacterial tetracycline formulations: host-modulators in the treatment of periodontitis and relevant systemic diseases","volume":"66","author":"Golub LM","year":"2016","journal-title":"Int Dent J"},{"key":"ref31","article-title":"RANKL expression in periodontal disease: where does RANKL come from?","author":"Chen B","year":"2014","journal-title":"Biomed Res Int"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"812","DOI":"10.22146\/jfps.8227","article-title":"Optimization of HPMC and Na-CMC as gelling agents on physical properties and stability in sunflower seed oil gel formulation","volume":"11","author":"Rahmani SIP","year":"2023","journal-title":"J Food Pharm Sci"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1055\/s-0040-1712718","article-title":"Cytokines and Chemokines in Periodontitis","volume":"14","author":"Ramadan DE","year":"2020","journal-title":"Eur J Dent"},{"issue":"31","key":"ref34","first-page":"62","article-title":"Study of Porphyromonas gingivalis in periodontal diseases: A Systematic review and meta-analysis","volume":"12","author":"Rafiei M","year":"2017","journal-title":"Med J Islam Repub Iran"},{"key":"ref35","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2020.110975","article-title":"Doxycycline restores the impaired osteogenic commitment of diabetic-derived bone marrow mesenchymal stromal cells by increasing the canonical WNT signaling","volume":"518","author":"Gomes PS","year":"2020","journal-title":"Mol Cell Endocrinol"},{"issue":"6","key":"ref36","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.52711\/0974-360X.2022.00442","article-title":"OPG and RANKL signal transduction in osteoblast regulation post application extract collagen in osteogenesis","volume":"5","author":"Kurnia S","year":"2022","journal-title":"Research J Pharm and Tech"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/1678-7757-2017-0326","article-title":"Alveolar bone healing in rats: micro-CT, immunohistochemical and molecular","volume":"26","author":"Hassumi JS","year":"2018","journal-title":"J Appl Oral Sci"},{"key":"ref38","first-page":"1","article-title":"Active compounds extraction of cocoa pod husk (Thebroma cacao L.) and potential as fungicides","volume":"1","author":"Rachmawaty A. Mu'nisa","year":"2018","journal-title":"Journal Of Physics: Conference Series"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.3390\/antiox9111136","article-title":"Osteoprotective roles of green tea catechins","volume":"9","author":"Huang HT","year":"2020","journal-title":"Antioxidants"},{"issue":"17","key":"ref40","first-page":"6605","article-title":"TNF-\u03b1 and RANKL promote osteoclastogenesis by upregulating RANK via the NF-\u03baB pathway","author":"Luo G","year":"2018","journal-title":"Mol Med Rep"}],"container-title":["Brazilian Dental Journal"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0103-64402024000100263&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T12:36:05Z","timestamp":1733142965000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0103-64402024000100263&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"references-count":40,"alternative-id":["S0103-64402024000100263"],"URL":"https:\/\/doi.org\/10.1590\/0103-6440202406015","relation":{},"ISSN":["1806-4760","0103-6440"],"issn-type":[{"type":"electronic","value":"1806-4760"},{"type":"print","value":"0103-6440"}],"subject":[],"published":{"date-parts":[[2024]]},"article-number":"e24-6015"}}