Immune suppressive properties of artemisinin family drugs

Hou, Lifei; Huang, Haochu

doi:10.1016/j.pharmthera.2016.07.002

Cited by 80 publications

(49 citation statements)

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“…This unique pharmacological mechanism endows ART distinct advantages of efficacy and safety in clinical application. Besides the anti-malarial functions, ART family drugs also exhibit anti-tumor [13-15], anti-viral [16], anti-inflammatory, and immune-suppressive activities [17, 18]. Artemisinin has been reported to abolish germinal center B cells and inhibit autoimmune arthritis in the K/BxN mouse model of rheumatoid arthritis [19].…”

Section: Introductionmentioning

confidence: 99%

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Zhong

Liang

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

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Section: Introductionmentioning

confidence: 99%

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Zhong

Liang

Yao

et al. 2018

Cell Physiol Biochem

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“…The role of artemisinin as an immunomodulator has drawn some attention in the recent years, with evidence of effects on both innate and adaptive immunity . Reports of positive effects on a range of autoimmune diseases and immune disorders have pointed to artemisinin as a promising immunoregulatory drug.…”

Section: Molecular Targets and Signaling Pathways Implicated In The Amentioning

confidence: 95%

“…The role of artemisinin as an immunomodulator has drawn some attention in the recent years, with evidence of effects on both innate and adaptive immunity. 12,98 Reports of positive effects on a range of autoimmune diseases and immune disorders have pointed to artemisinin as a promising immunoregulatory drug. In particular, artemisinin has been shown to exhibit immunosuppressive properties via the inhibition of T-cell activation and proliferation, as well as the ability to modulate regulatory T-cell (Treg) activity and cytokine production.…”

Section: Immunomodulation In Cancermentioning

confidence: 99%

Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

Wong

Kalesh

et al. 2017

Medicinal Research Reviews

202

139

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“…The highly oxygenated endoperoxide sesquiterpene lactone, artemisinin is an effective antimalarial compound that is derived from the Chinese medicinal plant Artemisia annua L. In view of the rapid development of parasite resistance to former antimalarial drugs, the World Health Organization (WHO) has endorsed the artemisinin-based combination therapies (ACTs) as the first-line treatment for uncomplicated malaria caused by Plasmodium falciparum [1, 2]. Apart from its antimalarial activities, artemisinin is also a multi-functional compound that is associated with a variety of novel biological properties, such as immunoregulatory [3], anticancer [4, 5], antituberculosis [6], antidiabetic [7], antiparasitic and antiviral functions [8].…”

Section: Introductionmentioning

confidence: 99%

Successes of artemisinin elicitation in low-artemisinin producing Artemisia annua cell cultures constrained by repression of biosynthetic genes

Yee

Ping

2019

Preprint

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10The sesquiterpene phytolactone derived from Artemisia annua, artemisinin is 11 associated with a variety of novel biological properties, such as immunoregulatory and 12 anticancer effects, and therapeutic applications, apart from its main function as an 13 4 57 Naturally, artemisinin biosynthesis occurs in glandular secretory trichomes that are 58 present on foliage, stems and inflorescences of the A. annua plant [15, 16]. Due to its 59 compartmentalized synthesis and influence by physiological, seasonal and environmental 60 factors, artemisinin concentration is highly variable with reported values of 0.1 -10 mg g -1 61 dry weight (DW) [11, 17]. With the biosynthetic pathway of artemisinin formation fully 62 elucidated over the past decade, it was learnt that within the species A. annua two contrasting 63 chemotypes can be distinguished, which are characterized by the differing contents of 64 artemisinin and its precursor (Fig 1). While both possess artemisinin, the high-artemisinin 65 producing (HAP) chemotype contains relatively higher levels of dihydroartemisinic acid 66 (DHAA) and artemisinin, and the low-artemisinin producing (LAP) chemotype has higher 67 contents of artemisinic acid and arteannuin B (a non-antimalarial product) [18, 19]. Despite 68 the difference in biochemical phenotype which is attributed to the differential expression of 69 one artemisinin biosynthesis specific gene artemisinic aldehyde Δ11(13) reductase (DBR2), 70 both chemotypes undergo similar spontaneous photooxidation reactions to produce 71 artemisinin or arteannuin B from its direct precursors [20-23]. 72 Fig 1. Schematic representation of artemisinin biosynthesis. 73 Synthesis occurs in the glandular trichome secretory cells of A. annua and sequestration of 74 artemisinin takes place in the subcuticular space. The two branching pathways leading to 75 artemisinin and arteannuin B of the artemisinin biosynthetic pathway (dashed line box) are 76 depicted and the final non-enzymatic photo-oxidation reaction is shown in red. MEP, 77 methylerythritol 4-phosphate; MVA, mevalonate; GST, glandular secretory trichome; ADS, 78 amorpha-4,11-diene synthase; CYP71AV1, cytochrome P450 monooxygenase; DBR2, 79 artemisinic aldehyde Δ11(13) reductase; ALDH1, aldehyde dehydrogenase 1. 80 As a secondary metabolite used mainly in defence mechanisms, production of 81 artemisinin would naturally be induced and enhanced under environmental stresses. Under 5 82 such adverse conditions the elevation of secondary oxidative stress, which is a consequence 83 of primary biotic/abiotic stress, is in a direct synergistic relationship with artemisinin 84 production [24-27]. On such basis, the biotechnological method elicitation which mimics the 85 natural induction of plant stress is the method of choice to enhance the production of 86 artemisinin. The positive effects of UV-B and DMSO on the production of artemisinin had 87 been verified by previous studies on A. annua seedlings [28, 29], in vitro propagated plantlets 88 [30] and shoot cultures [31]. Former st...

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Immune suppressive properties of artemisinin family drugs

Cited by 80 publications

References 55 publications

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

Successes of artemisinin elicitation in low-artemisinin producing Artemisia annua cell cultures constrained by repression of biosynthetic genes

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