Zhu Sipin, Sun Ping, Bennett Samuel, Charlesworth Oscar, Tan Renxiang, Peng Xing, Gu Qiang, Kujan Omar, Xu Jiake
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
Front Pharmacol. 2023 Mar 9;14:1111218. doi: 10.3389/fphar.2023.1111218. eCollection 2023.
Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic investigations reveal that PTL predominantly inhibits NF-κB activation and other signalling pathways, such as reactive oxygen species. As an inhibitor of NF-κB, PTL appears to inhibit several cytokines, including RANKL, TNF-α, IL-1β, together with LPS induced activation of NF-κB and NF-κB -mediated specific gene expression such as IL-1β, TNF-α, COX-2, iNOS, IL-8, MCP-1, RANTES, ICAM-1, VCAM-1. It is also proposed that PTL could inhibit cytokine storms or hypercytokinemia triggered by COVID-19 blocking the activation of NF-κB signalling. Understanding the pharmacologic properties of PTL will assist us in developing its therapeutic application for medical conditions, including arthritis, osteolysis, periodontal disease, cancers, and COVID-19-related disease.
小白菊内酯（PTL 或 PAR）最初是从广玉兰中分离出来的，并被鉴定为一种小分子癌症抑制剂。PTL 的化学结构为 C15H20O3，具有倍半萜内酯的特性，并表现出抑制癌细胞 DNA 生物合成的生物学特性。在本综述中，我们总结了药用 PTL 的最新研究进展，包括其对骨骼疾病、癌症和炎症诱导的细胞因子风暴的治疗作用。机制研究表明，PTL 主要抑制 NF-κB 激活和其他信号通路，如活性氧。作为 NF-κB 的抑制剂，PTL 似乎抑制多种细胞因子，包括 RANKL、TNF-α、IL-1β，以及 LPS 诱导的 NF-κB 激活和 NF-κB 介导的特定基因表达，如 IL-1β、TNF-α、COX-2、iNOS、IL-8、MCP-1、RANTES、ICAM-1、VCAM-1。还提出 PTL 可以通过阻断 NF-κB 信号通路的激活来抑制 COVID-19 引发的细胞因子风暴或高细胞因子血症。了解 PTL 的药理特性将有助于我们开发其在包括关节炎、骨质溶解、牙周疾病、癌症和 COVID-19 相关疾病等医疗状况中的治疗应用。
