PMID- 38396794 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20240227 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 4 DP - 2024 Feb 9 TI - The Role of Rosavin in the Pathophysiology of Bone Metabolism. LID - 10.3390/ijms25042117 [doi] LID - 2117 AB - Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor kappa B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions. FAU - Wojdasiewicz, Piotr AU - Wojdasiewicz P AUID- ORCID: 0000-0003-3309-996X AD - Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland. FAU - Turczyn, Pawel AU - Turczyn P AUID- ORCID: 0000-0001-6219-6422 AD - Department of Early Arthritis, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartanska 1, 02-637 Warsaw, Poland. FAU - Lach-Gruba, Anna AU - Lach-Gruba A AD - Department of Rehabilitation, St. Anna's Trauma Surgery Hospital, Mazovian Rehabilitation Center-STOCER, Barska 16/20, 02-315 Warsaw, Poland. FAU - Poniatowski, Lukasz A AU - Poniatowski LA AD - Department of Neurosurgery, Dietrich-Bonhoeffer-Klinikum, Salvador-Allende-Strasse 30, 17036 Neubrandenburg, Germany. FAU - Purrahman, Daryush AU - Purrahman D AUID- ORCID: 0000-0002-8215-2686 AD - Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. FAU - Mahmoudian-Sani, Mohammad-Reza AU - Mahmoudian-Sani MR AD - Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. FAU - Szukiewicz, Dariusz AU - Szukiewicz D AUID- ORCID: 0000-0002-0124-060X AD - Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland. LA - eng PT - Journal Article PT - Review DEP - 20240209 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 1R72C0ROME (rosavin) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) RN - 0 (NF-kappa B) RN - EC 3.4.- (Metalloproteases) RN - 0 (RANK Ligand) RN - 0 (NFATC Transcription Factors) RN - 0 (Disaccharides) SB - IM MH - Animals MH - Mice MH - *Osteoclasts/metabolism MH - Tartrate-Resistant Acid Phosphatase/metabolism MH - Osteogenesis MH - *Bone Resorption/metabolism MH - Cell Differentiation MH - NF-kappa B/metabolism MH - Metalloproteases/metabolism MH - RANK Ligand/metabolism MH - NFATC Transcription Factors/metabolism MH - *Disaccharides PMC - PMC10889099 OTO - NOTNLM OT - Rhodiola rosea OT - adaptogens OT - bone loss OT - bone metabolism OT - osteoblasts OT - osteoclastogenesis OT - osteogenesis OT - osteoporosis OT - rosavin COIS- The authors declare no conflict of interest. EDAT- 2024/02/24 11:45 MHDA- 2024/02/26 06:44 PMCR- 2024/02/09 CRDT- 2024/02/24 01:03 PHST- 2024/01/02 00:00 [received] PHST- 2024/02/04 00:00 [revised] PHST- 2024/02/07 00:00 [accepted] PHST- 2024/02/26 06:44 [medline] PHST- 2024/02/24 11:45 [pubmed] PHST- 2024/02/24 01:03 [entrez] PHST- 2024/02/09 00:00 [pmc-release] AID - ijms25042117 [pii] AID - ijms-25-02117 [pii] AID - 10.3390/ijms25042117 [doi] PST - epublish SO - Int J Mol Sci. 2024 Feb 9;25(4):2117. doi: 10.3390/ijms25042117.