Artemisia annua inhibits the growth of malignant tumors
Dihydroartemisinin: A Potential Drug for the Treatment of Malignancies and Inflammatory Diseases. 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.
Dihydroartemisinin (DHA), a derivative of artemisinin, is the active metabolite of artemisinin-like compounds in vivo (1, 2). DHA is widely used in the clinical treatment of malaria and has saved countless lives, due to its 100% efficiency against malaria parasites and low toxicity. DHA kills plasmodium parasites by damaging their membranes, disrupting their mitochondrial function and causing oxidative stress through producing excessive reactive oxide species (ROS) (3, 4). In addition to directly killing malaria parasites, it has recently been found that DHA enhances the ability of the immune system to resist parasites, such as malaria parasites and toxoplasma gondii. Jagannathan et al. find that Ugandan children who receive DHA preventative administration from 6 to 24 months old have a lower incidence of malaria, more IL-2+CD4+ T cells and TNF-α+CD4+ T cells, and fewer IL-10+CD4+ T cells than their peers who do not receive DHA (5). Zhang and colleagues find that DHA increases the number of T-helper (Th) cells and CD8+ T cells and the levels of IL-5 and IL-22, decreases the number of B cells and the content of some inflammatory cytokines, including TNF-α, IFN-γ, IL-2, IL-4, IL-6, and IL-10 in the mice who are infected with Toxoplasma gondii or Plasmodium Berghei (6). The above studies show that DHA can not only directly kill parasites, but also prevent hosts from parasitic diseases by regulating T cell subsets and cytokines production.
With the development of DHA research, it has been found that DHA has the pharmacological effect of anti-tumor and inhibition inflammation (7–12). Our laboratory has investigated the anti-tumor and inhibition inflammation effects of DHA and conducts a preliminary analysis of its mechanisms. It has been found that DHA inhibits the growth and metastasis of melanoma in mice by several ways (13). In addition, DHA also significantly alleviates imiquimod-induced mice psoriatic lesions (14). The pharmacological effects of DHA on tumors, pathogen infections, etc. over the past decades have been described in the review of Ho et al. (15), Efferth (16) and Slezakova et al. (17). Therefore, this article will review the last advances in DHA anti-tumor (Table 1) and anti-inflammation (Table 2) studies in recent years.