Artemisinins and immune system

Shakir, Lubna; Hussain, Muzammal; Javeed, Aqeel; Ashraf, Muhammad; Riaz, Amjad

doi:10.1016/j.ejphar.2011.06.044

Cited by 50 publications

(30 citation statements)

References 83 publications

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“…Due to the regulatory role of multiple signaling pathways, artemisinin has been shown to exert anti-inflammatory and anti-catabolic effects in various disease models25. Artemisinin was shown to alleviate neuroinflammation in a model of Alzheimer’s disease26.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

Jiang

Meng

Lee

et al. 2016

Sci Rep

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Osteoarthritis is a disease with inflammatory and catabolic imbalance in cartilage. Dihydroartemisinin (DHA), a natural and safe anti-malarial agent, has been reported to inhibit inflammation, but its effects on chondrocytes have yet to be elucidated. We investigated the effects of DHA on catabolism in chondrocytes. Viability of SD rats chondrocytes was analyzed. Autophagy levels were determined via expression of autophagic markers LC3 and ATG5, GFP-LC3 analysis, acridine orange staining, and electron microscopy. ATG5 siRNA induced autophagic inhibition. Catabolic gene and chemokine expression was evaluated using qPCR. The NF-κB inhibitor SM7368 and p65 over-expression were used to analyze the role of NF-κB pathway in autophagic activation. A concentration of 1 μM DHA without cytotoxicity increased LC3-II and ATG5 levels as well as autophagosomal numbers in chondrocytes. DHA inhibited TNF-α-induced expression of MMP-3 and -9, ADAMTS5, CCL-2 and -5, and CXCL1, which was reversed by autophagic inhibition. TNF-α-stimulated nuclear translocation and degradation of the p65 and IκBα proteins, respectively, were attenuated in DHA-treated chondrocytes. NF-κB inhibition activated autophagy in TNF-α-treated chondrocytes, but p65 over-expression reduced the autophagic response to DHA. These results indicate that DHA might suppress the levels of catabolic and inflammatory factors in chondrocytes by promoting autophagy via NF-κB pathway inhibition.

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Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

Jiang

Meng

Lee

et al. 2016

Sci Rep

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“…In this regard, we conducted experiments with CHQ and ART for three reasons; first, they are reported to inhibit pathways crucial for polarization to M2 type; second, they are widely used for treatment of malaria; and third, they possess immunomodulatory properties. ART have been reported to decrease IL‐10, IL‐1β, IL‐6, and TNF‐α levels (Shakir, Hussain, Javeed, Ashraf, & Riaz, ; Wu et al., ) through MAPK (Wang et al., ), NF‐κB (Prato, Gallo, Giribaldi, Aldieri, & Arese, ; Wang et al., ), and PI3K‐AKT (Kim et al., ) pathways. CHQ has also been demonstrated to act through MAPK (Kono et al., ; Weber, Chen, & Levitz, ) and NF‐κB(Long, Liu, Wang, Zhou, & Zheng, ; Yang et al., ) pathways and decrease IL‐1β, IL‐6, and TNF‐α in mononuclear phagocytes in different diseases (Jang et al., ; Long et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, falciparum malaria pathogenesis has been related to upregulated angiogenic factors VEGF, Ang‐2, and sFLT‐1 along with dysregulated and excessive immune responses (Muehlenbachs, Mutabingwa, Edmonds, Fried, & Duffy, ; Silver, Higgins, McDonald, & Kain, ). The antiparasitic action of ART is accompanied with disruption of parasite proteins, alteration of mitochondrial functions, and angiogenesis (Ak, ; Shakir et al., ). In relation to ability of M2 phenotype to stimulate angiogenesis, ART may attenuate Hz‐induced M2‐like phenotype by altering the release of angiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

et al. 2018

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Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment-hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro- and anti-inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2-like phenotype as evidenced by the expression of M2 signature markers. Hz-fed MO showed elevated transcript and secreted level of IL-10, CCL17, CCL1, expression of mannose-binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA-DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF-κB signaling pathways in skewing of Hz-fed MO toward M2-like type and suppression of mitogen-stimulated lymphocyte proliferation. Importantly, antimalarial drugs-chloroquine and artemisinin-partially reversed activation of Hz-induced MO toward M2-like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re-examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria.

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“…They induce an anti-inflammatory effect, neutropenia, and reduction in macrophage number and functions, which may produce immunosuppression. Artemisinins also have the ability to induce immunosuppression by inhibiting delayed-type hypersensitivity, lymphocyte proliferation, and a rise in antibody level (51). Immune deviation caused by chloroquine and other antimalarial drugs has been reported (52,53).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Murine Cerebral Malaria by Artemisone in Combination with Conventional Antimalarial Drugs: Antiplasmodial Effects and Immune Responses

Guiguemde

Hunt

Guo

et al. 2014

Antimicrob Agents Chemother

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dThe decreasing effectiveness of antimalarial therapy due to drug resistance necessitates constant efforts to develop new drugs. Artemisinin derivatives are the most recent drugs that have been introduced and are considered the first line of treatment, but there are already indications of Plasmodium falciparum resistance to artemisinins. Consequently, drug combinations are recommended for prevention of the induction of resistance. The research here demonstrates the effects of novel combinations of the new artemisinin derivative, artemisone, a recently described 10-alkylamino artemisinin derivative with improved antimalarial activity and reduced neurotoxicity. We here investigate its ability to kill P. falciparum in a high-throughput in vitro assay and to protect mice against lethal cerebral malaria caused by Plasmodium berghei ANKA when used alone or in combination with established antimalarial drugs. Artemisone effects against P. falciparum in vitro were synergistic with halofantrine and mefloquine, and additive with 25 other drugs, including chloroquine and doxycycline. The concentrations of artemisone combinations that were toxic against THP-1 cells in vitro were much higher than their effective antimalarial concentration. Artemisone, mefloquine, chloroquine, or piperaquine given individually mostly protected mice against cerebral malaria caused by P. berghei ANKA but did not prevent parasite recrudescence. Combinations of artemisone with any of the other three drugs did completely cure most mice of malaria. The combination of artemisone and chloroquine decreased the ratio of proinflammatory (gamma interferon, tumor necrosis factor) to anti-inflammatory (interleukin 10 [IL-10], IL-4) cytokines in the plasma of P. berghei-infected mice. Thus, artemisone in combinations with other antimalarial drugs might have a dual action, both killing parasites and limiting the potentially deleterious host inflammatory response.

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Artemisinins and immune system

Cited by 50 publications

References 83 publications

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway

Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin

Treatment of Murine Cerebral Malaria by Artemisone in Combination with Conventional Antimalarial Drugs: Antiplasmodial Effects and Immune Responses

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