{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:36:48Z","timestamp":1790030208884,"version":"4.0.1"},"reference-count":87,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ESSECORE SRL"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Osteoarthritis (OA) is a joint disease characterized by inflammation of the synovium, angiogenesis, cartilage degradation, and osteophyte formation. Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum) are plants which extracts, together to Bromelain and Escin (Aesculus hippocastanum) are traditionally used in OA. However, their mechanistic role remains unclear. We aimed to investigate whether these bioactives alone or in combination (as in Flonat Fast\u00ae) can suppress TNF-\u03b1-induced inflammation, angiogenesis, and osteophyte formation using two cell models involved in OA: endothelial cells and monocytes. Each plant extract was evaluated for its polyphenol content, antioxidant activity, and toxicity. In endothelial cells and monocytes, expression of genes involved in OA was assessed, functional assays for inflammation and angiogenesis were performed, and impairment of reactive oxygen species production (ROS) was evaluated. Exposure of cells to the bioactives alone and in combination before cytokine stimulation resulted in differential counterregulation of several gene and protein expressions, including those for cyclooxygenases-2, metalloproteinase-9, transforming growth factor \u03b21, and bone morphogenic protein-2. We demonstrated that these bioactives modulated monocyte adhesion to endothelial cells as well as cell migration and endothelial angiogenesis. Consistent with radical scavenging activity in the cell-free system, the bioactives curbed TNF-\u03b1-stimulated intracellular ROS production. We confirmed the potential anti-inflammatory and antiangiogenic effects of the combination of Harpagophytum procumbens, Boswellia, Curcuma, Bromelain, and Escin and provided new mechanistic evidence for their use in OA. However, further clinical studies are needed to evaluate the true clinical utility of these bioactives as supportive, preventive, and therapeutic agents.<\/jats:p>","DOI":"10.3390\/ph15101263","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T22:21:11Z","timestamp":1665699671000},"page":"1263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Analysis of the Anti-Inflammatory and Anti-Osteoarthritic Potential of Flonat Fast\u00ae, a Combination of Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum), Evaluated in In Vitro Models of Inflammation Relevant to Osteoarthritis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1589-4177","authenticated-orcid":false,"given":"Stefano","family":"Quarta","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Santarpino","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Paracelsus Medical University, 90471 Nuremberg, Germany"},{"name":"GVM Care & Research, Citt\u00e0 di Lecce Hospital, 73100 Lecce, Italy"},{"name":"Cardiac Surgery Unit, Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8307-1829","authenticated-orcid":false,"given":"Maria Annunziata","family":"Carluccio","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-2081","authenticated-orcid":false,"given":"Nadia","family":"Calabriso","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2753-8487","authenticated-orcid":false,"given":"Egeria","family":"Scoditti","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-3674","authenticated-orcid":false,"given":"Luisa","family":"Siculella","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7828-9519","authenticated-orcid":false,"given":"Fabrizio","family":"Damiano","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-4534","authenticated-orcid":false,"given":"Michele","family":"Maffia","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4983-2767","authenticated-orcid":false,"given":"Tiziano","family":"Verri","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-574X","authenticated-orcid":false,"given":"Raffaele","family":"De Caterina","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy"},{"name":"Cardiology Division, Pisa University Hospital, 56126 Pisa, Italy"},{"name":"Fondazione VillaSerena per la Ricerca, Citt\u00e0 Sant\u2019Angelo, 65013 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Massaro","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), National Research Council (CNR), 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","article-title":"The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis","volume":"6","author":"Sellam","year":"2010","journal-title":"Nat. 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