Orcinol glucoside targeted p38 as an agonist to promote osteogenesis and protect glucocorticoid-induced osteoporosis

He, Xiangming; Zhao, Wei; Yao, Liping; Sun, Peng; Cheng, Gang; Liu, Yuling; Yu, Yanke; Liu, Na; Wang, T Y; Zhang, Qiaoyan; Qin, Lu‐Ping; Zhang, Quanlong

doi:10.1016/j.phymed.2023.154953

Cited by 10 publications

(2 citation statements)

References 34 publications

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“…These results indicated that DEN alleviated the inhibitory effect of dexamethasone on the P-Jun and P-p38 expression after cotreatment for 3, 7, and 14 days ( P < 0.05, P < 0.01, Figure G). Considering that JNK and p38 pathway could block the effect of GC by inhibiting the nuclear translocation of GR, , the effect of DEN on the nucleation of GR by immunofluorescence was investigated. Dexamethasone increased the transfer of GR into the nucleus, but after 3 days of treatment with DEN, GR nuclear translocation was significantly reduced ( P < 0.01, Figure H).…”

Section: Resultsmentioning

confidence: 99%

“…JNK and p38 inhibitors eliminated the osteogenic protective effect of DEN on dexamethasone-treated BMSCs. Activation of JNK and p38 lead to decreased GR function through phosphorylation. , Here, we addressed that dexamethasone enhanced the nuclear translocation of GR; however, inhibition of JNK or p38 did not significantly affect this change induced by dexamethasone treatment. In conclusion, DEN ameliorates GC-induced bone loss and cell osteoblastic inhibition by promoting JNK and p38 MAPK pathways and restraining GR nuclear translocation.…”

Section: Discussionmentioning

confidence: 96%

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Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition

Li,

Gao,

Zhou

et al. 2024

J. Agric. Food Chem.

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Glucocorticoid-induced osteoporosis (GIOP) is the common reason for secondary osteoporosis. Dendrobine (DEN) is the major biologically active component of Dendrobium of f icinale with anti-inflammatory and antiaging properties. Whether DEN could alleviate osteogenic inhibition in GIOP rats is still unknown. The influence on osteogenic function caused by DEN on dexamethasone-treated bone marrow mesenchymal stem cells and rats was observed. The in vitro results showed that DEN reversed the inhibition of osteogenic differentiation by dexamethasone. Moreover, DEN supplementation attenuated dexamethasone-induced bone loss in vivo. DEN activated JNK and p38 MAPK pathways and restrained GR nuclear translocation, which could be prevented by the JNK (SP600125) or p38 (SB203580) pathway inhibitor. This study verified that DEN alleviated dexamethasone-induced nuclear translocation of GR, and inhibition of osteogenesis via JNK and p38 pathways, laying the foundation for DEN as a therapeutic agent for GIOP.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition

Li,

Gao,

Zhou

et al. 2024

J. Agric. Food Chem.

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Comparison of the Glucocorticoid Receptor Binding and Agonist Activities of Typical Glucocorticoids: Insights into Their Endocrine Disrupting Effects

Liang,

Li,

Zhang

et al. 2024

Chemistry & Biodiversity

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Over the past decades, the synthetic glucocorticoids (GCs) have been widely used in clinical practice and animal husbandry. Given the health hazard of these toxic residues in food, it is necessary to explore the detailed interaction mechanisms of typical GCs and their main target glucocorticoid receptor (GR). Hence, this work compared the GR binding and agonist activities of typical GCs. Fluorescence polarization assay showed that these GCs were potent ligands of GR. Their GR binding affinities were in the order of methylprednisolone > betamethasone ≈ prednisolone > dexamethasone, with IC50 values of 1.67, 2.94, 2.95, and 5.58 nM. Additionally, the limits of detection of dexamethasone, betamethasone, prednisolone, and methylprednisolone were 0.32, 0.14, 0.19, and 0.09 μg/kg in fluorescence polarization assay. Reporter gene assay showed that these GCs induced GR transactivation in a dose‐dependent manner, confirming their GR agonist activities. Among which, dexamethasone at the concentration of 100 nM produced a maximal induction of more than 11‐fold over the blank control. Molecular docking and molecular dynamics simulations suggested that hydrogen‐bonding and hydrophobic interactions played an important role in stabilizing the GC‐GR‐LBD complexes. In summary, this work might help to understand the GR‐mediated endocrine disrupting effects of typical GCs.

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Glaucatotones A−I: Guaiane-type sesquiterpenoids from the roots of Lindera glauca with anti-inflammatory activity

Pan,

Cai,

Liu

et al. 2024

Bioorganic Chemistry

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Orcinol glucoside targeted p38 as an agonist to promote osteogenesis and protect glucocorticoid-induced osteoporosis

Cited by 10 publications

References 34 publications

Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition

Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition

Comparison of the Glucocorticoid Receptor Binding and Agonist Activities of Typical Glucocorticoids: Insights into Their Endocrine Disrupting Effects

Glaucatotones A−I: Guaiane-type sesquiterpenoids from the roots of Lindera glauca with anti-inflammatory activity

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