Exploring the Potential Mechanism of Artemisinin and Its Derivatives in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

Abstract

Objective. This study is aimed at predicting and contrasting the mechanisms of artemisinin (ARS), dihydroartemisinin (DHA), artesunate (ART), artemether (ARM), and arteether (ARE) in the treatment of osteoporosis (OP) using network pharmacology and molecular docking. Methods. The targets of ARS, DHA, ART, ARM, and ARE were obtained from the SwissTargetPrediction. The targets related to OP were obtained from the TTD, DrugBank, Genecards, and DisGeNet databases. Then, the anti-OP targets of ARS, DHA, ART, ARM, and ARE were obtained and compared using the Venn diagram. Afterward, the protein-protein interaction (PPI) networks were built using the STRING database, and Cytoscape was used to select hub targets. Moreover, molecular docking validated the binding association between five molecules and hub targets. Finally, GO enrichment and KEGG pathway enrichment were conducted using the DAVID database. The common pathways of five molecules were analysed. Results. A total of 28, 37, 36, 27, and 33 anti-OP targets of ARS, DHA, ART, ARM, and ARE were acquired. EGFR, EGFR, CASP3, MAPK8, and CASP3 act as the top 1 anti-OP targets of ARS, DHA, ART, ARM, and ARE, respectively. MAPK14 is the common target of five molecules. All five molecules can bind well with these hubs and common targets. Meanwhile, functional annotation showed that MAPK, Serotonergic synapse, AMPK, prolactin, and prolactin signaling pathways are the top 1 anti-OP pathway of ARS, DHA, ART, ARM, and ARE, respectively. IL-17 signaling pathway and prolactin signaling pathway are common anti-OP pathways of five molecules. Besides, GO enrichment showed five biological processes and three molecular functions are common anti-OP mechanisms of five molecules. Conclusion. ARS, DHA, ART, ARM and ARE can treat OP through multi-targets and multi pathways, respectively. All five molecules can treat OP by targeting MAPK14 and acting on the IL-17 and prolactin signaling pathways.

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation

“…Artesunate, a semi-synthetic artemisinin derivative of sesquiterpene lactone, is an antimalarial drug used to treat orthopedic diseases like rheumatoid arthritis, osteoarthritis, and OP ( Li J et al, 2015 ; Ma et al, 2019 ; Ma Y et al, 2022 ). Artesunate accelerates osteoblast differentiation and alleviates OP via miR-34a/DKK1 axis regulation ( Zeng et al, 2020 ).…”

Traditional Chinese Medicine Offers New Ideas for the Treatment of Osteoporosis Through Multi-method Interventions in Ferroptosis

“…In particular, the effects of TCM on iron overload and ROS are significant for the prevention and treatment of osteoporosis. Most TCM practitioners believe that osteoporosis is mainly due to a deficiency of internal organs, and its treatment is mostly based on syndrome differentiation to “supplement its deficiency.” Modern pharmacology has shown that some of the TCM methods, such as Zanthoxylum bungeanum (Kim et al, 2010; Zhang et al, 2020), Epimedium (Fu et al, 2022; He et al, 2022; Wu et al, 2022), Salvia miltiorrhiza (Wang et al, 2022), Curcuma longa (Chai et al, 2021), Astragalus membranaceus (Lai et al, 2021), Artemisia carvifolia (Ma et al, 2022), Taohongsiwu decoction (Deng et al, 2020; Zhang et al, 2017; Zhou et al, 2017; Zhu et al, 2020), Sijunzi decoction (Chen, 2021), and Bushen Huanjing recipe (Huang et al, 2022), in which the active ingredients of those above and external treatment of TCM can affect the function of osteoblasts and osteoclasts, promote bone formation, and inhibit bone resorption. And most of the above TCM methods have been shown to influence the prevention and treatment of many diseases by interfering with ferroptosis.…”