Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress
Secondary osteoporosis is commonly caused by long-term intake of glucocorticoids (GCs), such as dexamethasone (DEX). Diosmin, a natural substance with potent antioxidant and anti-inflammatory properties, is clinically used for treating some vascular disorders. The current work targeted exploring the...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223002494 |
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| author | El-Shaimaa A. Arafa Noran O. Elgendy Mai A. Elhemely Eglal A. Abdelaleem Wafaa R. Mohamed |
| author_facet | El-Shaimaa A. Arafa Noran O. Elgendy Mai A. Elhemely Eglal A. Abdelaleem Wafaa R. Mohamed |
| author_sort | El-Shaimaa A. Arafa |
| collection | DOAJ |
| description | Secondary osteoporosis is commonly caused by long-term intake of glucocorticoids (GCs), such as dexamethasone (DEX). Diosmin, a natural substance with potent antioxidant and anti-inflammatory properties, is clinically used for treating some vascular disorders. The current work targeted exploring the protective properties of diosmin to counteract DEX-induced osteoporosis in vivo. Rats were administered DEX (7 mg/kg) once weekly for 5 weeks, and in the second week, vehicle or diosmin (50 or 100 mg/kg/day) for the next four weeks. Femur bone tissues were collected and processed for histological and biochemical examinations. The study findings showed that diosmin alleviated the histological bone impairments caused by DEX. In addition, diosmin upregulated the expression of Runt-related transcription factor 2 (Runx2) and phosphorylated protein kinase B (p-AKT) and the mRNA transcripts of Wingless (Wnt) and osteocalcin. Furthermore, diosmin counteracted the rise in the mRNA levels of receptor activator of nuclear factor-kB ligand (RANKL) and the reduction in osteoprotegerin (OPG), both were induced by DEX. Diosmin restored the oxidant/antioxidant equilibrium and exerted significant antiapoptotic activity. The aforementioned effects were more pronounced at the dose level of 100 mg/kg. Collectively, diosmin has proven to protect rats against DEX-induced osteoporosis by augmenting osteoblast and bone development while hindering osteoclast and bone resorption. Our findings could be used as a stand for recommending supplementation of diosmin for patients chronically using GCs. |
| first_indexed | 2024-04-09T21:02:24Z |
| format | Article |
| id | doaj.art-e54a8e8c93294d3dba19c524add400e5 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T21:02:24Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-e54a8e8c93294d3dba19c524add400e52023-03-29T09:22:24ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-05-01161114461Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stressEl-Shaimaa A. Arafa0Noran O. Elgendy1Mai A. Elhemely2Eglal A. Abdelaleem3Wafaa R. Mohamed4College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates; Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Corresponding author at: College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Department of Clinical Pharmacy, Beni-Suef University Hospital, Faculty of Medicine, Beni-Suef University, Beni-Suef, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M20 4GJ, United KingdomDepartment of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Corresponding author.Secondary osteoporosis is commonly caused by long-term intake of glucocorticoids (GCs), such as dexamethasone (DEX). Diosmin, a natural substance with potent antioxidant and anti-inflammatory properties, is clinically used for treating some vascular disorders. The current work targeted exploring the protective properties of diosmin to counteract DEX-induced osteoporosis in vivo. Rats were administered DEX (7 mg/kg) once weekly for 5 weeks, and in the second week, vehicle or diosmin (50 or 100 mg/kg/day) for the next four weeks. Femur bone tissues were collected and processed for histological and biochemical examinations. The study findings showed that diosmin alleviated the histological bone impairments caused by DEX. In addition, diosmin upregulated the expression of Runt-related transcription factor 2 (Runx2) and phosphorylated protein kinase B (p-AKT) and the mRNA transcripts of Wingless (Wnt) and osteocalcin. Furthermore, diosmin counteracted the rise in the mRNA levels of receptor activator of nuclear factor-kB ligand (RANKL) and the reduction in osteoprotegerin (OPG), both were induced by DEX. Diosmin restored the oxidant/antioxidant equilibrium and exerted significant antiapoptotic activity. The aforementioned effects were more pronounced at the dose level of 100 mg/kg. Collectively, diosmin has proven to protect rats against DEX-induced osteoporosis by augmenting osteoblast and bone development while hindering osteoclast and bone resorption. Our findings could be used as a stand for recommending supplementation of diosmin for patients chronically using GCs.http://www.sciencedirect.com/science/article/pii/S0753332223002494OsteoporosisGlucocorticoidsDiosminRANKL/OPGRunx-2Oxidative stress |
| spellingShingle | El-Shaimaa A. Arafa Noran O. Elgendy Mai A. Elhemely Eglal A. Abdelaleem Wafaa R. Mohamed Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress Biomedicine & Pharmacotherapy Osteoporosis Glucocorticoids Diosmin RANKL/OPG Runx-2 Oxidative stress |
| title | Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress |
| title_full | Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress |
| title_fullStr | Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress |
| title_full_unstemmed | Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress |
| title_short | Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress |
| title_sort | diosmin mitigates dexamethasone induced osteoporosis in vivo role of runx2 rankl opg and oxidative stress |
| topic | Osteoporosis Glucocorticoids Diosmin RANKL/OPG Runx-2 Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223002494 |
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