Artemisinin and its derivatives are widely used in the world as the first‐line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti‐inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions.

Background and purpose:  The C–C chemokine receptor CCR5, and the C–X–C chemokine receptor CXCR3 are involved in the regulation of T cell‐mediated immune responses, and in the migration and activation of these cells. To determine whether blockade of these chemokine receptors modulated inflammatory responses in the central nervous sytem (CNS), we investigated the effect of a non‐peptide chemokine receptor antagonist, TAK‐779, in mice with experimental autoimmune encephalomyelitis (EAE).Experimental approach:  EAE was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG) 35–55. TAK‐779 was injected s.c. once a day after immunization. Disease incidence and severity (over 3 weeks) were monitored by histopathological evaluation and FACS assay of inflammatory cells infiltrating into the spinal cord, polymerase chain reaction quantification of mRNA expression, assay of T cell proliferation, by [³H]‐thymidine incorporation and cytokine production by enzyme‐linked immunosorbent assay.Key results:  Treatment with TAK‐779 reduced incidence and severity of EAE. It strongly inhibited migration of CXCR3/CCR5 bearing CD4⁺, CD8⁺ and CD11b⁺ leukocytes to the CNS. TAK‐779 did not reduce proliferation of anti‐MOG T cells, the production of IFN‐γ by T cells or CXCR3 expression on T cells. In addition, TAK‐779 did not affect production of IL‐12 by antigen‐presenting cells, CCR5 induction on T cells and the potential of MOG‐specific T cells to transfer EAE.Conclusions and implications:  TAK‐779 restricted the development of MOG‐induced EAE. This effect involved reduced migration of inflammatory cells into the CNS without affecting responses of anti‐MOG T cells or the ability of MOG‐specific T cells to transfer EAE.

Shikonin is a naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon, which has displayed potent anti-tumor properties. However, the effects of shikonin in colorectal cancer cells have not been yet fully investigated. In this study, we demonstrated that shikonin significantly inhibited the activity of colorectal cancer cells in a time- and dose-dependent manner. The flow cytometry and western blot results indicated that shikonin induced cell apoptosis by down-regulating BCL-2 and activating caspase-3/9 and the cleavage of PARP. The expression of BiP and the PERK/elF2α/ATF4/CHOP and IRE1α /JNK signaling pathways were upregulated after shikonin treatment. The pre-treatment with N-acetyl cysteine significantly reduced the cytotoxicity of shikonin. Taken together, shikonin could inhibit proliferation of the colorectal cancer cell through the activation of ROS mediated-ER stress. The in vivo results showed that shikonin effectively inhibited tumor growth in the HCT-116 and HCT-15 xenograft models. In conclusion, shikonin inhibited the proliferation of colorectal cancer cells in vitro and in vivo and warrants future investigation.

Eutypenoids A–C (1–3), pimarane diterpenoid alkaloid and two ring A rearranged pimarane diterpenoids, were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures, including absolute configurations, were authenticated on the basis of the mass spectroscopy (MS), nuclear magnetic resonance (NMR), X-ray crystallography, and electronic circular dichroism (ECD) analysis. The immunosuppressive effects of eutypenoids A–C (1–3) were studied using a ConA-induced splenocyte proliferation model, which suggested that 2 exhibited potent immunosuppressive activities.