Kuangyang Yang , Qian Xie , Tingting Tang , Na Zhao , Jianhui Liang , Yanni Shen , Ziqi Li , Ben Liu , Jianhai Chen , Wenxiang Cheng , Xueling Bai , Peng Zhang , Qian Liu , Bing Song , Chun Hu , Lichu Liu , Yan Wang
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The CXCR4 antagonistic activity was evaluated by calcium response in THP-1 cells. Signaling pathway study was conducted by bulk RNA sequencing and western blot analysis in human C28/I2 chondrocytes. The anti-OA activity was evaluated in monosodium iodoacetate (MIA)-induced rats.</p></div><div><h3>Results</h3><p>Astragaloside IV (ASN IV), the predominate phytochemical in <em>Astragalus membranaceus</em>, has been identified as a novel CXCR4 antagonist. ASN IV reduced CXCL12-induced ADAMTS4,5 overexpression in chondrocytes through blocking Akt signaling pathway. Furthermore, ASN IV administration significantly repaired the damaged cartilage and subchondral bone in MIA-induced rats.</p></div><div><h3>Conclusion</h3><p>The blockade of CXCR4 signaling by ASN IV could explain anti-OA activities of <em>Astragalus membranaceus</em> by protection of cartilage degradation in OA patients. Since ASN IV as an antiviral has been approved by China National Medical Products Administration for testing in people, repurposing of ASN IV as a joint protective agent might be a promising strategy for OA drug development.</p></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"108 ","pages":"Article 154506"},"PeriodicalIF":8.3000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats\",\"authors\":\"Kuangyang Yang , Qian Xie , Tingting Tang , Na Zhao , Jianhui Liang , Yanni Shen , Ziqi Li , Ben Liu , Jianhai Chen , Wenxiang Cheng , Xueling Bai , Peng Zhang , Qian Liu , Bing Song , Chun Hu , Lichu Liu , Yan Wang\",\"doi\":\"10.1016/j.phymed.2022.154506\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and Purpose</h3><p>C-X-C chemokine receptor type 4 (CXCR4) inhibition protects cartilage in osteoarthritis (OA) animal models. 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引用次数: 4
摘要
背景与目的抑制sec - x - c趋化因子受体4型(CXCR4)对骨关节炎(OA)动物模型软骨的保护作用。因此,CXCR4已成为OA药物开发的新靶点。由于膳食和草药补充剂已广泛用于关节健康,我们假设一些补充剂通过抑制CXCR4信号传导对OA软骨具有保护作用。方法采用Scanpy 1.9.0软件对OA患者(GSE152805)单细胞RNA测序数据进行重新分析。CXCR4拮抗剂对接筛选采用Autodock Vina 1.2.0进行。通过THP-1细胞的钙反应来评价CXCR4的拮抗活性。采用大体积RNA测序和western blot方法对人C28/I2软骨细胞的信号通路进行研究。以碘乙酸钠(MIA)诱导大鼠为实验对象,观察其抗oa活性。结果黄芪甲苷(asstraagaloside IV, ASN IV)是一种新型的CXCR4拮抗剂,是黄芪中主要的植物化学物质。ASN IV通过阻断Akt信号通路降低cxcl12诱导的adamts4,5在软骨细胞中的过表达。此外,ASN IV可显著修复mia诱导大鼠受损的软骨和软骨下骨。结论ASN - 4阻断CXCR4信号通路可以解释黄芪通过保护OA患者软骨退化而具有抗OA作用。由于ASN IV作为抗病毒药物已被中国国家药品监督管理局批准用于人体试验,ASN IV作为联合保护剂的再利用可能是OA药物开发的一个有前途的策略。
Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats
Background and Purpose
C-X-C chemokine receptor type 4 (CXCR4) inhibition protects cartilage in osteoarthritis (OA) animal models. Therefore, CXCR4 has becoming a novel target for OA drug development. Since dietary and herbal supplements have been widely used for joint health, we hypothesized that some supplements exhibit protective effects on OA cartilage through inhibiting CXCR4 signaling.
Methods
The single-cell RNA sequencing data of OA patients (GSE152805) was re-analyzed by Scanpy 1.9.0. The docking screening of CXCR4 antagonists was conducted by Autodock Vina 1.2.0. The CXCR4 antagonistic activity was evaluated by calcium response in THP-1 cells. Signaling pathway study was conducted by bulk RNA sequencing and western blot analysis in human C28/I2 chondrocytes. The anti-OA activity was evaluated in monosodium iodoacetate (MIA)-induced rats.
Results
Astragaloside IV (ASN IV), the predominate phytochemical in Astragalus membranaceus, has been identified as a novel CXCR4 antagonist. ASN IV reduced CXCL12-induced ADAMTS4,5 overexpression in chondrocytes through blocking Akt signaling pathway. Furthermore, ASN IV administration significantly repaired the damaged cartilage and subchondral bone in MIA-induced rats.
Conclusion
The blockade of CXCR4 signaling by ASN IV could explain anti-OA activities of Astragalus membranaceus by protection of cartilage degradation in OA patients. Since ASN IV as an antiviral has been approved by China National Medical Products Administration for testing in people, repurposing of ASN IV as a joint protective agent might be a promising strategy for OA drug development.
期刊介绍:
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.