Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production
Osteoporosis represents an imbalance between bone formation and bone resorption. As a result of low estrogen levels, it is markedly prevalent during menopause, thus making such patients susceptible to fractures. Both bone formation and resorption are modulated by nitric oxide (NO). Currently, there...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Osteoporosis |
| Online Access: | http://dx.doi.org/10.1155/2019/1592328 |
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| author | Rebecca A. Rajfer Manuel Flores Andrea Abraham Eduardo Garcia Natalhy Hinojosa Mina Desai Jorge N. Artaza Monica G. Ferrini |
| author_facet | Rebecca A. Rajfer Manuel Flores Andrea Abraham Eduardo Garcia Natalhy Hinojosa Mina Desai Jorge N. Artaza Monica G. Ferrini |
| author_sort | Rebecca A. Rajfer |
| collection | DOAJ |
| description | Osteoporosis represents an imbalance between bone formation and bone resorption. As a result of low estrogen levels, it is markedly prevalent during menopause, thus making such patients susceptible to fractures. Both bone formation and resorption are modulated by nitric oxide (NO). Currently, there are no risk-free pharmaceutical prevention therapies for osteoporosis. COMB-4, a nutraceutical combination of Paullinia cupana, Muira puama, ginger, and L-citrulline, known to activate the NO-cGMP pathway, was reported to accelerate fracture healing in the rat. To determine whether COMB-4 could be effective in preventing menopausal osteoporosis, it was compared to estradiol (E2) in an ovariectomized (OVX) rat osteoporosis model. Nine-month-old female Sprague Dawley rats were divided into SHAM, OVX, OVX+E2, and OVX+COMB-4. After 100 days of treatment, bone mineral density (BMD) and bone mineral content (BMC) were measured by DXA scan. TRAP staining was performed in the femur and lumbar vertebrae. TRACP 5b and osteocalcin levels were assayed in the serum. MC3T3-E1 cells were differentiated into osteoblasts and treated with COMB-4 for one week in order to evaluate calcium deposition by Alizarin staining, cGMP production by ELISA, and upregulation of the nitric oxide synthase (NOS) enzymes by RT-PCR. OVX resulted in a decrease in BMD, BMC, and serum osteocalcin and an increase in serum TRACP 5b. Except for an increase in BMC with COMB-4, both E2 and COMB-4 reverted all bone and serum markers, as well as the number of osteoclasts in the vertebrae, to SHAM levels. Incubation of MC3T3-E1 cells with COMB-4 demonstrated an increase in the three NOS isoforms, cGMP, and calcium deposition. COMB-4 increased BMD in OVX rats by inhibiting bone resorption and increasing calcium deposition presumably via activation of the NO-cGMP pathway. It remains to be determined whether COMB-4 could be a potential nutraceutical therapy for the prevention of premenopausal bone loss. |
| format | Article |
| id | doaj-art-aede6b35909a4498bf78f93b96efc93c |
| institution | Kabale University |
| issn | 2090-8059 2042-0064 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Osteoporosis |
| spelling | doaj-art-aede6b35909a4498bf78f93b96efc93c2025-08-20T03:39:00ZengWileyJournal of Osteoporosis2090-80592042-00642019-01-01201910.1155/2019/15923281592328Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide ProductionRebecca A. Rajfer0Manuel Flores1Andrea Abraham2Eduardo Garcia3Natalhy Hinojosa4Mina Desai5Jorge N. Artaza6Monica G. Ferrini7Department of Orthopedic Surgery, Loma Linda University, Loma Linda, CA, USADepartment of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USADepartment of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USADepartment of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USADepartment of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USAPerinatal Research Laboratory, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USADepartment of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USADepartment of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USAOsteoporosis represents an imbalance between bone formation and bone resorption. As a result of low estrogen levels, it is markedly prevalent during menopause, thus making such patients susceptible to fractures. Both bone formation and resorption are modulated by nitric oxide (NO). Currently, there are no risk-free pharmaceutical prevention therapies for osteoporosis. COMB-4, a nutraceutical combination of Paullinia cupana, Muira puama, ginger, and L-citrulline, known to activate the NO-cGMP pathway, was reported to accelerate fracture healing in the rat. To determine whether COMB-4 could be effective in preventing menopausal osteoporosis, it was compared to estradiol (E2) in an ovariectomized (OVX) rat osteoporosis model. Nine-month-old female Sprague Dawley rats were divided into SHAM, OVX, OVX+E2, and OVX+COMB-4. After 100 days of treatment, bone mineral density (BMD) and bone mineral content (BMC) were measured by DXA scan. TRAP staining was performed in the femur and lumbar vertebrae. TRACP 5b and osteocalcin levels were assayed in the serum. MC3T3-E1 cells were differentiated into osteoblasts and treated with COMB-4 for one week in order to evaluate calcium deposition by Alizarin staining, cGMP production by ELISA, and upregulation of the nitric oxide synthase (NOS) enzymes by RT-PCR. OVX resulted in a decrease in BMD, BMC, and serum osteocalcin and an increase in serum TRACP 5b. Except for an increase in BMC with COMB-4, both E2 and COMB-4 reverted all bone and serum markers, as well as the number of osteoclasts in the vertebrae, to SHAM levels. Incubation of MC3T3-E1 cells with COMB-4 demonstrated an increase in the three NOS isoforms, cGMP, and calcium deposition. COMB-4 increased BMD in OVX rats by inhibiting bone resorption and increasing calcium deposition presumably via activation of the NO-cGMP pathway. It remains to be determined whether COMB-4 could be a potential nutraceutical therapy for the prevention of premenopausal bone loss.http://dx.doi.org/10.1155/2019/1592328 |
| spellingShingle | Rebecca A. Rajfer Manuel Flores Andrea Abraham Eduardo Garcia Natalhy Hinojosa Mina Desai Jorge N. Artaza Monica G. Ferrini Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production Journal of Osteoporosis |
| title | Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production |
| title_full | Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production |
| title_fullStr | Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production |
| title_full_unstemmed | Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production |
| title_short | Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production |
| title_sort | prevention of osteoporosis in the ovariectomized rat by oral administration of a nutraceutical combination that stimulates nitric oxide production |
| url | http://dx.doi.org/10.1155/2019/1592328 |
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