Liuwei Dihuang Pills alleviates postmenopausal osteoporosis and fatigue in rats by inhibiting the epigenetic regulatory molecule BRD4 pathway
OBJECTIVE: To explore the role of epigenetic signal molecule bromodomain protein 4 (BRD4) in mediating the therapeutic effect of Liuwei Dihuang (LWDH) Pills on postmenopausal osteoporosis (PMOP) and fatigue.
METHODS: Thirty rat models of PMOP induced by bilateral ovariectomy were randomized equally into two groups for treatment with normal saline (model group) or LWDH Pills (385.7 mg/kg), with another 15 sham-operated rats as the sham operation group. After 12 weeks of treatment, femoral samples were taken to determine the bone density and BRD4 protein expression. The weight-bearing exhaustive swimming time of the rat models was recorded, and serum levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured using enzyme-linked immunosorbent assay. In cultured primary osteoblasts the changes in the expressions of BRD4, MAPK and NF-κB proteins were detected by immunofluorescence staining following treatment with LWDH Pills.
RESULTS: The rat models of PMOP showed significantly up-regulated expression of BRD4 protein in the femoral tissue (P < 0.05), which was obviously lowered by treatment with LWDH Pills. The rats treated with LWDH Pills also showed significant improvement of fatigue. Immunofluorescent staining of the osteoblasts showed that treatment with LWDH Pills significantly decreased the protein expressions of BRD4, MAPK and NF-κB. Analysis of the GSE56116 dataset revealed that that patients with kidney-yin deficiency had significantly higher BRD4 expression than those in the kidney-yang-deficiency group and non-kidney-deficiency group (P < 0.05). The upregulation of BRD4 expression involved multiple signaling pathways including neural ligand receptor response, cytoskeleton rearrangement, cytokine interaction, and granulocyte colony-stimulating factor chemotaxis pathways.
CONCLUSION: LWDH can alleviate PMOP and fatigue by decreasing BRD4 signaling pathway, suggesting that potential of BRD4 as a promising therapeutic target for PMOP.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
|---|---|
| Enthalten in: |
Nan fang yi ke da xue xue bao = Journal of Southern Medical University - 43(2023), 12 vom: 20. Dez., Seite 1998-2005 |
| Sprache: |
Chinesisch |
|---|
| Beteiligte Personen: |
Ruan, H [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.01.2024 Date Revised 11.01.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.12122/j.issn.1673-4254.2023.12.02 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366800043 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366800043 | ||
| 003 | DE-627 | ||
| 005 | 20240114233920.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240114s2023 xx |||||o 00| ||chi c | ||
| 024 | 7 | |a 10.12122/j.issn.1673-4254.2023.12.02 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1256.xml |
| 035 | |a (DE-627)NLM366800043 | ||
| 035 | |a (NLM)38189384 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a chi | ||
| 100 | 1 | |a Ruan, H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Liuwei Dihuang Pills alleviates postmenopausal osteoporosis and fatigue in rats by inhibiting the epigenetic regulatory molecule BRD4 pathway |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.01.2024 | ||
| 500 | |a Date Revised 11.01.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To explore the role of epigenetic signal molecule bromodomain protein 4 (BRD4) in mediating the therapeutic effect of Liuwei Dihuang (LWDH) Pills on postmenopausal osteoporosis (PMOP) and fatigue | ||
| 520 | |a METHODS: Thirty rat models of PMOP induced by bilateral ovariectomy were randomized equally into two groups for treatment with normal saline (model group) or LWDH Pills (385.7 mg/kg), with another 15 sham-operated rats as the sham operation group. After 12 weeks of treatment, femoral samples were taken to determine the bone density and BRD4 protein expression. The weight-bearing exhaustive swimming time of the rat models was recorded, and serum levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured using enzyme-linked immunosorbent assay. In cultured primary osteoblasts the changes in the expressions of BRD4, MAPK and NF-κB proteins were detected by immunofluorescence staining following treatment with LWDH Pills | ||
| 520 | |a RESULTS: The rat models of PMOP showed significantly up-regulated expression of BRD4 protein in the femoral tissue (P < 0.05), which was obviously lowered by treatment with LWDH Pills. The rats treated with LWDH Pills also showed significant improvement of fatigue. Immunofluorescent staining of the osteoblasts showed that treatment with LWDH Pills significantly decreased the protein expressions of BRD4, MAPK and NF-κB. Analysis of the GSE56116 dataset revealed that that patients with kidney-yin deficiency had significantly higher BRD4 expression than those in the kidney-yang-deficiency group and non-kidney-deficiency group (P < 0.05). The upregulation of BRD4 expression involved multiple signaling pathways including neural ligand receptor response, cytoskeleton rearrangement, cytokine interaction, and granulocyte colony-stimulating factor chemotaxis pathways | ||
| 520 | |a CONCLUSION: LWDH can alleviate PMOP and fatigue by decreasing BRD4 signaling pathway, suggesting that potential of BRD4 as a promising therapeutic target for PMOP | ||
| 650 | 4 | |a English Abstract | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Liuwei Dihuang Pills | |
| 650 | 4 | |a bromodomain protein 4 | |
| 650 | 4 | |a fatigue | |
| 650 | 4 | |a postmenopausal osteoporosis | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a BRD4 protein, human |2 NLM | |
| 650 | 7 | |a Bromodomain Containing Proteins |2 NLM | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 700 | 1 | |a She, D |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nan fang yi ke da xue xue bao = Journal of Southern Medical University |d 2006 |g 43(2023), 12 vom: 20. Dez., Seite 1998-2005 |w (DE-627)NLM16087646X |x 1673-4254 |7 nnns |
| 773 | 1 | 8 | |g volume:43 |g year:2023 |g number:12 |g day:20 |g month:12 |g pages:1998-2005 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.12122/j.issn.1673-4254.2023.12.02 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 43 |j 2023 |e 12 |b 20 |c 12 |h 1998-2005 | ||