Dihydroartemisinin (DHA) has been globally recognized for its efficacy and safety in the clinical treatment of malaria for decades. Recently, it has been found that DHA inhibits malignant tumor growth and regulates immune system function in addition to anti-malaria. In parasites and tumors, DHA causes severe oxidative stress by inducing excessive reactive oxygen species production. DHA also kills tumor cells by inducing programmed cell death, blocking cell cycle and enhancing anti-tumor immunity. In addition, DHA inhibits inflammation by reducing the inflammatory cells infiltration and suppressing the production of pro-inflammatory cytokines. Further, genomics, proteomics, metabolomics and network pharmacology of DHA therapy provide the basis for elucidating the pharmacological effects of DHA. This review provides a summary of the recent research progress of DHA in anti-tumor, inhibition of inflammatory diseases and the relevant pharmacological mechanisms. With further research of DHA, it is likely that DHA will become an alternative therapy in the clinical treatment of malignant tumors and inflammatory diseases.

It has been shown that dihydroartemisinin (DHA) is effective in the treatment of malaria. Recently studies have demonstrated that DHA also regulates tumor cell growth, angiogenesis, T cell differentiation and generation. However, how DHA affects melanoma development remains poorly defined. To investigate the effects of DHA on the proliferation and migration of melanoma in vivo and in vitro, and to explore its possible mechanism. B16F10 cells and melanoma-bearing BALB/c mice were used to investigate the effects of DHA on melanoma. DHA had inhibitory effect on melanoma proliferation in a time-and dose-dependent manner. Treatment of DHA attenuated melanoma severity and histopathological changes in BALB/c mice. DHA also inhibited melanoma invasion, migration, and community formation in a dose-dependent manner. Flow cytometry revealed a significant increase in IFN-γ⁺CD8⁺ T cells in the DHA groups. In tumor microenvironment and spleen, DHA induced expansion of CD8⁺CTL, while, CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells and IL-10⁺CD4⁺CD25⁺ T cells were normalized by DHA treatment. DHA diminished expression of IL-10 and IL-6, and increased the expression of IFN-γ in the tumor and spleen. Moreover, DHA administration significantly promoted the mitochondrial apoptosis of melanoma by regulating the STAT3 pathway. DHA induces mitochondrial apoptosis and alters cytokines expression by inhibiting the phosphorylation of STAT3. DHA improves anti-tumor immunity in mice through controlling CD8⁺CTL function by counteracting IL-10-dependent Treg cells suppression, which promises to be an alternative drug for melanoma.

Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein–protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell–cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1β. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1β were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis.

Tumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti‐angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA‐treated supernatants significantly inhibited the tubule‐forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF‐1α/VEGF, PI3K/ATK/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non‐targeted metabolomics analysis revealed that DHA‐treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.

Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism.Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo.Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17⁺CD4⁺T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role.Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8⁺CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8⁺CTLs. Moreover, DHA impacts STAT3-induced EMT and MMP_S in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma in vitro and in vivo. These results have important implications for the potential use of DHA in the treatment of melanoma in humans.