Toosendanin inhibits osteoclast formation and alleviate postmenopausal osteoporosis by regulating the p38 signaling pathway

Tan, Tingting; Li, Tao; Cheng, Xiang; Ouyang, Zhengxiao

doi:10.1016/j.intimp.2023.109745

Cited by 7 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent research has shown that TSN possesses diverse beneficial effects in animal experiments, including a broad-spectrum anti-cancer activity [29], anti-obesity effects [30], anti-viral properties [31], and anti-inflammatory and anti-colitis effects [32]. Furthermore, a recent study demonstrated that TSN suppresses osteoclast formation and attenuates osteoporosis in an ovariectomized mouse model [33]. This study has shown that treatment of osteoclast precursor cells with TSN inhibits RANKL-stimulated expression of c-Fos and NFATc1 by suppressing the activation of p38 mitogen-activated protein kinase (MAPK), subsequently inhibiting the expression of osteoclast-specific genes and osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus

Kim,

Gu,

Yang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Melia toosendan fructus, traditionally employed in traditional Chinese and Korean herbal medicine, exhibits diverse biological properties encompassing anti-tumor, anti-inflammatory, and anti-viral effects. However, its influence on bone metabolism remains largely unexplored. In this study, we investigated the impact of an ethanolic extract of Melia toosendan fructus (MTE) on osteoclast differentiation and characterized its principal active constituent in osteoclast differentiation and function, as well as its effects on bone protection. Our findings demonstrate that MTE effectively inhibits the differentiation of osteoclast precursors induced by receptor activator of nuclear factor κB ligand (RANKL). Utilizing a bioassay-guided fractionation approach coupled with UHPLC-MS/MS analysis, we isolated and identified the triterpenoid compound toosendanin (TSN) as the active constituent responsible for MTE’s anti-osteoclastogenic activity. TSN treatment downregulated the expression of nuclear factor of activated T cells c1, a pivotal osteoclastogenic transcription factor, along with molecules implicated in osteoclast-mediated bone resorption, including tumor necrosis factor receptor-associated factor 6, carbonic anhydrase II, integrin beta-3, and cathepsin K. Furthermore, treatment of mature osteoclasts with TSN impaired actin ring formation, acidification, and resorptive function. Consistent with our in vitro findings, TSN administration mitigated trabecular bone loss and reduced serum levels of the bone resorption marker, C-terminal cross-linked telopeptides of type I collagen, in a mouse bone loss model induced by intraperitoneal injections of RANKL. These results suggest that TSN, as the principal active constituent of MTE with inhibitory effects on osteoclastogenesis, exhibits bone-protective properties by suppressing both osteoclast differentiation and function. These findings imply the potential utility of TSN in the treatment of diseases characterized by excessive bone resorption.

show abstract

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus

Kim,

Gu,

Yang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Wang et al discovered that BML-111, a synthetic lipoxin A4 agonist, effectively alleviated structural joint damage and inhibited osteoclast formation by reducing the activation of MAPK pathways (Wang et al 2023b ). Tan et al found that toosendanin (TSN) targeted and interfered with the activation of the p38 subunit, thereby regulating the MAPK cascade and inhibiting osteoclast formation (Tan et al 2023 ). Jiang et al demonstrated that PD0325901, a specific inhibitor of ERK, inhibited the expression of c-Fos and NFATc1, and suppressed osteoclast differentiation in a time-dependent and dose-dependent manner (Jiang et al 2023 ).…”

Section: The Rankl/rank Signaling Pathway Activates Nfatc1mentioning

confidence: 99%

Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets

Zheng,

Liu,

Deng

et al. 2024

Mol Med

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

show abstract

Therapeutic potential of toosendanin: Novel applications of an old ascaris repellent as a drug candidate

Hu,

Xu,

Chen

et al. 2023

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Toosendanin inhibits osteoclast formation and alleviate postmenopausal osteoporosis by regulating the p38 signaling pathway

Cited by 7 publications

References 35 publications

Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus

Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus

Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets

Therapeutic potential of toosendanin: Novel applications of an old ascaris repellent as a drug candidate

Contact Info

Product

Resources

About