The osteoprotective effects of artemisinin compounds and the possible mechanisms associated with intracellular iron: A review of in vivo and in vitro studies

Zhang, Jian

doi:10.1016/j.etap.2020.103358

Cited by 27 publications

(25 citation statements)

References 53 publications

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“…Nowadays, it is considered by the World Health Organization (WHO) as the only potent drug to combat Malaria in combination with quinoline derivatives (Artemisinin based combination therapies). Recently, researchers demonstrated the beneficial impact of artemisinin in various biochemical pathways in different dental cells such as dental pulp stem cells (DPSC), bone marrow-derived mesenchymal stem cells (BMSCs) and human mesenchymal stem cells (HMSCs) [ 35 , 36 ]. Hu et al [ 37 ] presented that artemisinin was able to restore the osteogenic differentiation of DPSCs under hypoxia conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Fang et al [ 38 ] observed the improvement of the in vitro survival of BMSCs after incubation with ART and especially when exposed to an ROS-induced environment, suggesting that artemisinin-mediated protection in BMSCs occurs via the activation of the c-Raf-Erk1/2-p90rsk-CREB signaling pathway. Zhang et al [ 35 ] demonstrated that artemisinin compounds have the ability to inhibit osteoclast differentiation using their intracellular iron, activating the cleavage of Endoperoxide Bridge, generating ROS and causing oxidative damage and ferroptosis. In light of these results, we propose the loading of synthesized mesoporous nanocarriers with ART to verify their potential capability to locally deliver this multifunctional drug.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts

et al. 2021

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Ion doping has rendered mesoporous structures important materials in the field of tissue engineering, as apart from drug carriers, they can additionally serve as regenerative materials. The purpose of the present study was the synthesis, characterization and evaluation of the effect of artemisinin (ART)-loaded cerium-doped mesoporous calcium silicate nanopowders (NPs) on the hemocompatibility and cell proliferation of human periodontal ligament fibroblasts (hPDLFs). Mesoporous NPs were synthesized in a basic environment via a surfactant assisted cooperative self-assembly process and were characterized using Scanning Electron Microscopy (SEM), X-ray Fluorescence Spectroscopy (XRF), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction Analysis (XRD) and N2 Porosimetry. The loading capacity of NPs was evaluated using Ultrahigh Performance Liquid Chromatography/High resolution Mass Spectrometry (UHPLC/HRMS). Their biocompatibility was evaluated with the MTT assay, and the analysis of reactive oxygen species was performed using the cell-permeable ROS-sensitive probe 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA). The synthesized NPs presented a mesoporous structure with a surface area ranging from 1312 m2/g for undoped silica to 495 m2/g for the Ce-doped NPs, excellent bioactivity after a 1-day immersion in c-SBF, hemocompatibility and a high loading capacity (around 80%). They presented ROS scavenging properties, and both the unloaded and ART-loaded NPs significantly promoted cell proliferation even at high concentrations of NPs (125 μg/mL). The ART-loaded Ce-doped NPs with the highest amount of cerium slightly restricted cell proliferation after 7 days of culture, but the difference was not significant compared with the control untreated cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts

et al. 2021

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“…Some drugs that target osteoporosis may actualize a ferroptotic role during the therapeutic mechanism, which, in our perspective, is reasonable to surmise, but not yet visible. Artemisinin (ARS) and its related compounds, which are already known as inhibitors of osteoporosis due to their suppression of osteoclast differentiation by blocking the receptor activator of nuclear factor kappa-B ligand (RANKL) pathway, may induce ferroptosis in osteoclasts due to the high levels of ferritin and LIP in osteoclasts (Zhang, 2020). Furthermore, andrographolide (AP), an herbal medicine, was found to have the ability to regulate the osteoprotegerin (OPG)/RANKL signal (Tantikanlayaporn et al, 2020) and stifle the NF-κB pathway activated by TNFα (Yongyun et al, 2019) so as to hasten osteoblast differentiation.…”

Section: Ferroptosis and Osteoporosismentioning

confidence: 99%

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Duan

Lin

et al. 2021

Front. Cell Dev. Biol.

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Ferroptosis is classified as an iron-dependent form of regulated cell death (RCD) attributed to the accumulation of lipid hydroperoxides and redox imbalance. In recent years, accumulating researches have suggested that ferroptosis may play a vital role in the development of diverse metabolic diseases, for example, diabetes and its complications (e.g., diabetic nephropathy, diabetic cardiomyopathy, diabetic myocardial ischemia/reperfusion injury and atherosclerosis [AS]), metabolic bone disease and adrenal injury. However, the specific physiopathological mechanism and precise therapeutic effect is still not clear. In this review, we summarized recent advances about the development of ferroptosis, focused on its potential character as the therapeutic target in metabolic diseases, and put forward our insights on this topic, largely to offer some help to forecast further directions.

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“…On the contrary, one of the most potent drugs involving the production of ROS mediated by iron is artemisinin (ART) and its derivatives, which contain an endoperoxide moiety that can be activated by iron to form cytotoxic reactive species. This characteristic was applied for many pathologies including malaria [ 9 ], cancer [ 10 ] and osteoporosis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…A similar mechanism of action for artemisinin has been observed for diseases associated to osteoporosis. In detail, ARTs revealed osteoprotective effects associated with excessive intracellular production of ROS, which leads to inhibition of osteoclast differentiation (responsible for bone loss) by blocking pathways involved in the receptor activator of nuclear factor kappa-B ligand (RANKL) and finally promoting osteogenesis [ 11 ]. Considering the characteristic of high levels of intracellular iron in osteoclasts, ART compounds could inhibit osteoclast differentiation via mechanisms associated with intracellular iron, as assumed for the ARTs treatment in malaria parasites.…”

Section: Introductionmentioning

confidence: 99%

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins

Tsamesidis

Pério

Pantaleo

et al. 2020

IJMS

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In red blood cells, hemoglobin iron represents the most plausible candidate to catalyze artemisinin activation but the limited reactivity of iron bound to hemoglobin does not play in favor for its direct involvement. Denatured hemoglobin appears a more likely candidate for artemisinin redox activation because it is expected to contain reactive iron and it has been described to release free heme and/or iron in erythrocyte. The aim of our study is to investigate, using three different methods: fluorescence, electron paramagnetic resonance and liquid chromatography coupled to mass spectrometry, how increasing the level of accessible iron into the red blood cells can enhance the reactive oxygen species (ROS) production derived from artemisinin. The over-increase of iron was achieved using phenylhydrazine, a strong oxidant that causes oxidative stress within erythrocytes, resulting in oxidation of oxyhemoglobin and leading to the formation of methemoglobin, which is subsequently converted into irreversible hemichromes (iron (III) compounds). Our findings confirmed, using the iron III chelator, desferrioxamine, the indirect participation of iron (III) compounds in the activation process of artemisinins. Furthermore, in strong reducing conditions, the activation of artemisinin and the consequent production of ROS was enhanced. In conclusion, we demonstrate, through the measurement of intra-erythrocytic superoxide and hydrogen peroxide production using various methods, that artemisinin activation can be drastically enhanced by pre-oxidation of erythrocytes.

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The osteoprotective effects of artemisinin compounds and the possible mechanisms associated with intracellular iron: A review of in vivo and in vitro studies

Cited by 27 publications

References 53 publications

Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts

Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins

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