KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK
The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB act...
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MDPI AG
2022-07-01
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| Series: | Nutrients |
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| author | Laura Salvadori Maria Laura Belladonna Beatrice Castiglioni Martina Paiella Eleonora Panfili Tommaso Manenti Catia Ercolani Luca Cornioli Sara Chiappalupi Giulia Gentili Massimiliano Leigheb Guglielmo Sorci Michela Bosetti Nicoletta Filigheddu Francesca Riuzzi |
| author_facet | Laura Salvadori Maria Laura Belladonna Beatrice Castiglioni Martina Paiella Eleonora Panfili Tommaso Manenti Catia Ercolani Luca Cornioli Sara Chiappalupi Giulia Gentili Massimiliano Leigheb Guglielmo Sorci Michela Bosetti Nicoletta Filigheddu Francesca Riuzzi |
| author_sort | Laura Salvadori |
| collection | DOAJ |
| description | The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized <i>Withania somnifera</i>, <i>Silybum marianum</i> and <i>Trigonella foenum-graecum</i> herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Β ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. <i>Withania somnifera</i> appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or <i>Withania somnifera</i>-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs. |
| first_indexed | 2024-03-09T05:07:17Z |
| format | Article |
| id | doaj.art-b44742cc88494c29b9e18b4b7391fcd2 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T05:07:17Z |
| publishDate | 2022-07-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-b44742cc88494c29b9e18b4b7391fcd22023-12-03T12:53:15ZengMDPI AGNutrients2072-66432022-07-011415305310.3390/nu14153053KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPKLaura Salvadori0Maria Laura Belladonna1Beatrice Castiglioni2Martina Paiella3Eleonora Panfili4Tommaso Manenti5Catia Ercolani6Luca Cornioli7Sara Chiappalupi8Giulia Gentili9Massimiliano Leigheb10Guglielmo Sorci11Michela Bosetti12Nicoletta Filigheddu13Francesca Riuzzi14Department Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment Medicine and Surgery, University of Perugia, 06132 Perugia, ItalyDepartment Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, ItalyDepartment Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyDepartment Medicine and Surgery, University of Perugia, 06132 Perugia, ItalyLaboratori Biokyma srl, 52031 Anghiari, ItalyLaboratori Biokyma srl, 52031 Anghiari, ItalyLaboratori Biokyma srl, 52031 Anghiari, ItalyInteruniversity Institute of Myology (IIM), 06132 Perugia, ItalyInteruniversity Institute of Myology (IIM), 06132 Perugia, ItalyDepartment of Health Sciences, University of Piemonte Orientale, 28100 Novara, ItalyInteruniversity Institute of Myology (IIM), 06132 Perugia, ItalyDepartment Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, ItalyDepartment Translational Medicine, University of Piemonte Orientale, 28100 Novara, ItalyInteruniversity Institute of Myology (IIM), 06132 Perugia, ItalyThe imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized <i>Withania somnifera</i>, <i>Silybum marianum</i> and <i>Trigonella foenum-graecum</i> herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Β ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. <i>Withania somnifera</i> appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or <i>Withania somnifera</i>-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs.https://www.mdpi.com/2072-6643/14/15/3053osteoclastRANKLosteoblastsignaling pathwaysnatural productage-related diseases |
| spellingShingle | Laura Salvadori Maria Laura Belladonna Beatrice Castiglioni Martina Paiella Eleonora Panfili Tommaso Manenti Catia Ercolani Luca Cornioli Sara Chiappalupi Giulia Gentili Massimiliano Leigheb Guglielmo Sorci Michela Bosetti Nicoletta Filigheddu Francesca Riuzzi KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK Nutrients osteoclast RANKL osteoblast signaling pathways natural product age-related diseases |
| title | KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK |
| title_full | KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK |
| title_fullStr | KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK |
| title_full_unstemmed | KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK |
| title_short | KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK |
| title_sort | kymasin up natural product inhibits osteoclastogenesis and improves osteoblast activity by modulating src and p38 mapk |
| topic | osteoclast RANKL osteoblast signaling pathways natural product age-related diseases |
| url | https://www.mdpi.com/2072-6643/14/15/3053 |
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