Mechanism of artesunate on bone destruction in experimental rheumatoid arthritis based on transcriptomics and network pharmacology / 中国中药杂志

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.

Artesunate promotes Th1 differentiation from CD4+ T cells to enhance cell apoptosis in ovarian cancer via miR-142

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

Current research analysis and prospects on sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy / 中国中药杂志

The wide application of artemisinins in the treatment of multiple cancers reflects the advantages of traditional Chinese medicine used in this field. The existing basic and clinical studies have revealed that artesunate can effectively suppress the malignant progression of breast cancer,colon cancer,leukemia,melanoma,ovarian cancer,prostate cancer,kidney cancer and various tumors in central nervous system. The pharmacological mechanisms of artesunate against cancers are reflected in many aspects,such as inhibiting tumor cell proliferation,invasion and metastasis,inducing tumor cell apoptosis and autophagy,regulating cell signal transduction and inhibiting tumor angiogenesis. Meanwhile,growing experimental evidences have indicated that artesunate has been used for the sensitization of radiotherapy with X-ray,β-ray,γ-ray and~(60)Co γ-ray,as well as chemotherapy with cisplatin,carboplatin and doxorubicin.This review collected basic and clinical studies on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy published on PubMed and CNKI during April 2000 and February 2019,and summarized the clinical positioning and application of artesunate,with the aim to provide a more comprehensive explanation on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy,and offer the inspiration and ideas for the development of radiotherapy and chemotherapy sensitizers,as well as cancer resistance reversal agents.