The therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm

Sipin Zhu; Ping Sun; Samuel Bennett; Oscar Charlesworth; Renxiang Tan; Xing Peng; Qiang Gu; Omar Kujan; Jiake Xu

doi:10.3389/fphar.2023.1111218

The therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm

Front Pharmacol. 2023 Mar 9:14:1111218. doi: 10.3389/fphar.2023.1111218. eCollection 2023.

Authors

Sipin Zhu^{1

2}, Ping Sun^{2

3}, Samuel Bennett², Oscar Charlesworth², Renxiang Tan⁴, Xing Peng⁵, Qiang Gu⁵, Omar Kujan⁶, Jiake Xu^{1

2}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
² School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
³ Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
⁴ The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, Nanjing University, Nanjing, China.
⁵ Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
⁶ UWA Dental School, The University of Western Australia, Perth, WA, Australia.

Abstract

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 via 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.

Keywords: cancers; inflammation; osteolysis; parthenolide; skeletal diseases.

Publication types

Review

Grants and funding

This work was partly supported by a research grant from the National Natural Science Funding of China (81802235), Zhejiang Experimental Animal Science and Technology Project of China (2018C37112), and Wenzhou basic science research plan project (Y20180033). This work was also partly supported by a collaborative research award (RCA, 2020) from The University of Western Australia (UWA). SZ and PS made overseas collaborative visits to UWA. OC was visiting student at JX’s lab at UWA.