Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway

doi:10.1002/ptr.8209

科研成果详情

题名	Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway
作者	Lou, Chao1,2; Fang, Yuqin1,2; Mei, Yifan3; Hu, Wei 1,2; Sun, Liaojun1,2; Jin, Chen1,2; Chen, Hua1,2; Zheng, Wenhao 1,2
发表日期	2024-04-20
发表期刊	Phytotherapy research : PTR 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	NLRP3 Nrf2 cucurbitacin B osteoarthritis pyroptosis
其他关键词	NF-KAPPA-B ; SYNOVIAL INFLAMMATION ; TARGET ; NRF2
摘要	Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod-like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro-inflammatory factors induced by interleukin-1β (IL-1β), including cyclooxygenase-2, inducible nitric oxide synthase, IL-1β, and IL-18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5. CuB protects cells by activating the Nrf2/hemeoxygenase-1 (HO-1) pathway and inhibiting nuclear factor-κB (NF-κB)/NLRP3 inflammasome-mediated pyroptosis. Moreover, in vivo experiments show that CuB can slow down cartilage degradation in an OA mouse model. CuB effectively prevents the progression of OA by inhibiting inflammation in chondrocytes and ECM degradation. This action is further mediated through the activation of the Nrf2/HO-1 pathway to inhibit NF-κB/NLRP3 inflammasome activation. Thus, CuB is a potential therapeutic agent for OA.
资助项目	Basic Public Welfare Research Project of Zhejiang Province[LQ24H060008];Zhejiang Medicine Health Science and Technology Program[2022RC209];Wenzhou Science and Technology Plan Project[2021Y0301];Wenzhou Science and Technology Plan Project[Y20210050];Wenzhou Science and Technology Plan Project[Y2023043]
出版者	WILEY
ISSN	0951-418X
EISSN	1099-1573
卷号	38 期号:7 页码:3352-3369
DOI	10.1002/ptr.8209
页数	18
WOS类目	Chemistry, Medicinal ; Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001205807400001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2024-04
URL	查看原文
PubMed ID	38642047
SCOPUSEID	2-s2.0-85191144089
通讯作者地址	[Jin, Chen]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,109 West Xueyuan Road, Zhejiang Province,Wenzhou,325027,China ; [Chen, Hua]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China ; [Zheng, Wenhao]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/211174
专题	第二临床医学院、附属第二医院、育英儿童医院附属第二医院_骨科重点学科实验室
通讯作者	Jin, Chen; Chen, Hua; Zheng, Wenhao
作者单位	1.Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 2.Wenzhou Medical University,Key Laboratory of Orthopaedics of Zhejiang Province,Wenzhou,China; 3.Department of Neurological Rehabilitation,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 温州医科大学
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Lou, Chao,Fang, Yuqin,Mei, Yifan,et al. Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway[J]. Phytotherapy research : PTR,2024,38(7):3352-3369.
APA	Lou, Chao., Fang, Yuqin., Mei, Yifan., Hu, Wei., Sun, Liaojun., ... & Zheng, Wenhao. (2024). Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway. Phytotherapy research : PTR, 38(7), 3352-3369.
MLA	Lou, Chao,et al."Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway".Phytotherapy research : PTR 38.7(2024):3352-3369.