In Vitro Insights into the Role of 7,8-Epoxy-11-Sinulariolide Acetate Isolated from Soft Coral in the Potential Attenuation of Inflammation and Osteoclastogenesis

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2024 Feb 23

PMID 38393066

Authors

Lin-Mao Ke

Dan-Dan Yu

Ming-Zhi Su

Liao Cui

Yue-Wei Guo

Affiliations

Soon will be listed here.

Abstract

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the process of bone remodeling. Excessive osteoclast differentiation plays a pivotal role in the pathogenesis of bone diseases such as rheumatoid arthritis and osteoporosis. In the present study, we examined whether 7,8-epoxy-11-sinulariolide acetate (Esa), a marine natural product present in soft coral , attenuates inflammation and osteoclastogenesis in vitro. The results indicated that Esa significantly inhibited lipopolysaccharide (LPS)-induced inflammation model of RAW264.7 cells and suppressed receptor activator for nuclear factor-κB ligand (RANKL)-triggered osteoclastogenesis. Esa significantly down-regulated the protein expression of iNOS, COX-2, and TNF-α by inhibiting the NF-κB/MAPK/PI3K pathways and reducing the release of reactive oxygen species (ROS) in RAW264.7 macrophages. Besides, Esa treatment significantly inhibited osteoclast differentiation and suppressed the expression of osteoclast-specific markers such as NFATC1, MMP-9, and CTSK proteins. These findings suggest that Esa may be a potential agent for the maintenance of bone homeostasis associated with inflammation.

References

Liu J, Li X, Wang H, Ren Y, Li Y, Guo F . Bavachinin selectively modulates PPAR γ and maintains bone homeostasis in Type 2 Diabetes. Phytother Res. 2023; 37(10):4457-4472. DOI: 10.1002/ptr.7912. View

Recker R, Lewiecki E, Miller P, Reiffel J . Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. 2009; 122(2 Suppl):S22-32. DOI: 10.1016/j.amjmed.2008.12.004. View

Hu Y, Zhou Q, Liu T, Liu Z . Coixol Suppresses NF-κB, MAPK Pathways and NLRP3 Inflammasome Activation in Lipopolysaccharide-Induced RAW 264.7 Cells. Molecules. 2020; 25(4). PMC: 7070437. DOI: 10.3390/molecules25040894. View

Vellucci R, Terenzi R, Kanis J, Kress H, Mediati R, Reginster J . Understanding osteoporotic pain and its pharmacological treatment. Osteoporos Int. 2018; 29(7):1477-1491. DOI: 10.1007/s00198-018-4476-y. View

Xiao L, Zhong M, Huang Y, Zhu J, Tang W, Li D . Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways. Aging (Albany NY). 2020; 12(21):21706-21729. PMC: 7695364. DOI: 10.18632/aging.103976. View

Zhang Y, Xie C, Wang Y, He X, Xie M, Li Y . Penidihydrocitrinins A-C: New Polyketides from the Deep-Sea-Derived W17 and Their Anti-Inflammatory and Anti-Osteoporotic Bioactivities. Mar Drugs. 2023; 21(10). PMC: 10608093. DOI: 10.3390/md21100538. View

Song Y, Yu D, Su M, Luo H, Cao J, Liang L . Structurally Diverse Diterpenes from the South China Sea Soft Coral . Mar Drugs. 2023; 21(2). PMC: 9960596. DOI: 10.3390/md21020069. View

Hu B, Wu F, Shi Z, He B, Zhao X, Wu H . Dehydrocostus lactone attenuates osteoclastogenesis and osteoclast-induced bone loss by modulating NF-κB signalling pathway. J Cell Mol Med. 2019; 23(8):5762-5770. PMC: 6653234. DOI: 10.1111/jcmm.14492. View

Xia Y, Inoue K, Du Y, Baker S, Reddy E, Greenblatt M . TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis. Nat Commun. 2022; 13(1):3920. PMC: 9263175. DOI: 10.1038/s41467-022-31475-1. View

10.

Wang C, Zhu X, Chen R, Zhang X, Lian N . Overexpression of SENP3 promotes PPAR-γ transcription through the increase of HIF-1α stability via SUMO2/3 and participates in molecular mechanisms of osteoporosis. Mol Cell Endocrinol. 2023; 577:112014. DOI: 10.1016/j.mce.2023.112014. View

11.

Cho S, Kim H, Jung H, Park J, Jang Y, Ahn J . Effect of Ishophloroglucin A Isolated from on In Vitro Osteoclastogenesis and Osteoblastogenesis. Mar Drugs. 2023; 21(7). PMC: 10381815. DOI: 10.3390/md21070377. View

12.

Zhang Y, Li Z, Huang B, Liu K, Peng S, Liu X . Anti-Osteoclastogenic and Antibacterial Effects of Chlorinated Polyketides from the Beibu Gulf Coral-Derived Fungus GXIMD 02505. Mar Drugs. 2022; 20(3). PMC: 8956104. DOI: 10.3390/md20030178. View

13.

Su M, Cao J, Huang J, Liu S, Im D, Yoo J . The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist. Mar Drugs. 2017; 15(1). PMC: 5295227. DOI: 10.3390/md15010007. View

14.

Li X, Lin X, Wu Z, Su Y, Liang J, Chen R . Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-κB and ERK Signaling Pathways. Drug Des Devel Ther. 2021; 15:61-74. PMC: 7800467. DOI: 10.2147/DDDT.S283694. View

15.

Qu Y, Liu X, Zong S, Sun H, Liu S, Zhao Y . Protocatechualdehyde Inhibits the Osteoclast Differentiation of RAW264.7 and BMM Cells by Regulating NF-B and MAPK Activity. Biomed Res Int. 2021; 2021:6108999. PMC: 8302381. DOI: 10.1155/2021/6108999. View

16.

Doi K, Murata K, Ito S, Suzuki A, Terao C, Ishie S . Role of Lysine-Specific Demethylase 1 in Metabolically Integrating Osteoclast Differentiation and Inflammatory Bone Resorption Through Hypoxia-Inducible Factor 1α and E2F1. Arthritis Rheumatol. 2022; 74(6):948-960. PMC: 9156537. DOI: 10.1002/art.42074. View

17.

Marshall J . The gastrointestinal tolerability and safety of oral bisphosphonates. Expert Opin Drug Saf. 2003; 1(1):71-8. DOI: 10.1517/14740338.1.1.71. View

18.

Yao Y, Cai X, Ren F, Ye Y, Wang F, Zheng C . The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases. Front Immunol. 2021; 12:664871. PMC: 8044404. DOI: 10.3389/fimmu.2021.664871. View

19.

Hassumi M, Silva-Filho V, Campos-Junior J, Vieira S, Cunha F, Alves P . PPAR-gamma agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis. Int Immunopharmacol. 2009; 9(10):1150-8. DOI: 10.1016/j.intimp.2009.06.002. View

20.

Ha Y, Choi Y, Oh Y, Kang E, Khang G, Park Y . Fucoxanthin Suppresses Osteoclastogenesis via Modulation of MAP Kinase and Nrf2 Signaling. Mar Drugs. 2021; 19(3). PMC: 7997314. DOI: 10.3390/md19030132. View