Chrysoeriol: a natural RANKL inhibitor targeting osteoclastogenesis and ROS regulation for osteoporosis therapy.

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Hao Luo, Sijian Lin, Hao Lv, Wen Tan, Junlong Zhong, Jiachao Xiong, ZhiMing Liu, Qin Wu, Ming Chen, Kai Cao
{"title":"Chrysoeriol: a natural RANKL inhibitor targeting osteoclastogenesis and ROS regulation for osteoporosis therapy.","authors":"Hao Luo, Sijian Lin, Hao Lv, Wen Tan, Junlong Zhong, Jiachao Xiong, ZhiMing Liu, Qin Wu, Ming Chen, Kai Cao","doi":"10.1007/s00210-024-03714-3","DOIUrl":null,"url":null,"abstract":"<p><p>Chrysoeriol (CHE) is a naturally occurring compound with established anti-inflammatory and anti-tumor effects. This study examines its potential role in regulating osteoclast differentiation and activity, both of which are crucial for bone remodeling. Computational docking revealed high binding affinity between CHE and RANKL, specifically at the Lys-181 residue of RANKL, suggesting potential inhibitory interactions on osteoclastogenesis. In vitro assays confirmed CHE's non-toxic profile at concentrations below 20 μM and demonstrated a dose-dependent suppression of osteoclast differentiation. Notably, CHE treatment significantly reduced TRAP activity and bone resorption capacity in a dose-dependent manner. Furthermore, CHE markedly decreased ROS production by NOX-1 expression and modulated the NRF2/KEAP1 pathway to enhance ROS clearance. The compound also showed inhibitory effects on the NF-κB and MAPK signaling pathways, which are crucial for osteoclast activation. In an ovariectomized mouse model, administration of CHE mitigated bone loss, indicating its therapeutic potential in osteoporosis. Collectively, these findings establish CHE as a promising natural therapeutic agent for treating bone disorders characterized by excessive bone resorption, underscoring the need for further clinical investigation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Naunyn-Schmiedeberg's archives of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00210-024-03714-3","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Chrysoeriol (CHE) is a naturally occurring compound with established anti-inflammatory and anti-tumor effects. This study examines its potential role in regulating osteoclast differentiation and activity, both of which are crucial for bone remodeling. Computational docking revealed high binding affinity between CHE and RANKL, specifically at the Lys-181 residue of RANKL, suggesting potential inhibitory interactions on osteoclastogenesis. In vitro assays confirmed CHE's non-toxic profile at concentrations below 20 μM and demonstrated a dose-dependent suppression of osteoclast differentiation. Notably, CHE treatment significantly reduced TRAP activity and bone resorption capacity in a dose-dependent manner. Furthermore, CHE markedly decreased ROS production by NOX-1 expression and modulated the NRF2/KEAP1 pathway to enhance ROS clearance. The compound also showed inhibitory effects on the NF-κB and MAPK signaling pathways, which are crucial for osteoclast activation. In an ovariectomized mouse model, administration of CHE mitigated bone loss, indicating its therapeutic potential in osteoporosis. Collectively, these findings establish CHE as a promising natural therapeutic agent for treating bone disorders characterized by excessive bone resorption, underscoring the need for further clinical investigation.

黄菊醇:一种天然的RANKL抑制剂,靶向破骨细胞生成和ROS调节,用于骨质疏松症治疗。
黄松醇(CHE)是一种天然存在的化合物,具有抗炎和抗肿瘤作用。本研究探讨了其在调节破骨细胞分化和活性方面的潜在作用,这两者对骨重塑都至关重要。计算对接显示CHE和RANKL之间的高结合亲和力,特别是在RANKL的Lys-181残基上,这表明CHE和RANKL之间可能存在抑制破骨细胞发生的相互作用。体外实验证实,CHE在浓度低于20 μM时无毒,并显示出剂量依赖性地抑制破骨细胞分化。值得注意的是,CHE治疗以剂量依赖的方式显著降低TRAP活性和骨吸收能力。此外,CHE通过NOX-1的表达显著降低ROS的产生,并调节NRF2/KEAP1通路,增强ROS清除。该化合物还显示出对破骨细胞活化至关重要的NF-κB和MAPK信号通路的抑制作用。在去卵巢小鼠模型中,给药CHE减轻了骨质流失,表明其在骨质疏松症中的治疗潜力。综上所述,这些发现表明CHE是一种很有前景的天然治疗剂,用于治疗以骨吸收过度为特征的骨疾病,强调了进一步临床研究的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信