Irilin D suppresses RANKL-induced osteoclastogenesis and prevents inflammation-induced bone loss by disrupting the NF-κB and MAPK signaling pathways

Gal, Minju; Tuan, Ha Manh; Park, Ju-Hee; Park, Kang-Hyeon; Kim, Okhwa; Min, Byung-Sun; Lee, Jeong-Hyung

doi:10.1016/j.ejphar.2024.176956

European Journal of Pharmacology

2024

DOI: 10.1016/j.ejphar.2024.176956

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Irilin D suppresses RANKL-induced osteoclastogenesis and prevents inflammation-induced bone loss by disrupting the NF-κB and MAPK signaling pathways

Minju Gal,

Ha Manh Tuan,

Ju-Hee Park

et al.

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Triterpenoids from Potentilla chinensis Inhibit RANKL‐Induced Osteoclastogenesis in Vitro and Lipopolysaccharide‐Induced Osteolytic Bone Loss in Vivo

Tran,

Gal,

et al. 2024

Chemistry & Biodiversity

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In this study, a phytochemical investigation on the methanol extract of Potentilla chinensis led to the isolation of eleven triterpenoids including ursolic acid (1), pomolic acid (2), tormentic acid (3), 2‐epi‐corosolic acid (4), 3‐epi‐corosolic acid (ECA, 5), 3β‐hydroxyurs‐11‐en‐13β(28)‐olide (6), euscaphic acid (7), 2‐epi‐tormentic acid (8), corosolic acid (9), uvaol (10), and 3‐O‐acetylpomolic acid (11). Among them, ECA (5) showed potential anti‐osteoclastogenic activity. To the best of our knowledge, this represents the first isolation of ECA (5) from P. chinensis as well as the first investigation of its effects on osteoclast formation. Further study revealed that ECA inhibited RANKL‐induced mature osteoclast formation in vitro without compromising cell viability. Mechanistically, ECA attenuated RANKL‐induced mitogen‐activated protein kinases (MAPKs) and nuclear factor‐κB (NF‐κB) activation, leading to the inhibition of c‐Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) activation. Moreover, ECA protected against LPS‐induced inflammatory bone loss and osteoclast formation in a mouse model. However, ECA did not inhibit LPS‐induced inflammatory responses in macrophages. Our findings suggest that ECA mitigates LPS‐induced inflammatory bone loss in mice by inhibiting RANKL‐induced activation of key osteoclastogenic transcription factors, including c‐Fos and NFATc1, and may be a potential natural triterpenoid for preventing or treating osteolytic diseases.

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Triterpenoids from Potentilla chinensis Inhibit RANKL‐Induced Osteoclastogenesis in Vitro and Lipopolysaccharide‐Induced Osteolytic Bone Loss in Vivo

Tran,

Gal,

et al. 2024

Chemistry & Biodiversity

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show abstract

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Irilin D suppresses RANKL-induced osteoclastogenesis and prevents inflammation-induced bone loss by disrupting the NF-κB and MAPK signaling pathways

Cited by 1 publication

References 40 publications

Triterpenoids from Potentilla chinensis Inhibit RANKL‐Induced Osteoclastogenesis in Vitro and Lipopolysaccharide‐Induced Osteolytic Bone Loss in Vivo

Triterpenoids from Potentilla chinensis Inhibit RANKL‐Induced Osteoclastogenesis in Vitro and Lipopolysaccharide‐Induced Osteolytic Bone Loss in Vivo

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