PMID: 

Zhonghua Xue Ye Xue Za Zhi. 2019 Mar 14 ;40(3):204-208. PMID: 30929387

Abstract Title: 

[Effects of artesunate combined with bortezomib on apoptosis and autophagy of acute myeloid leukemia cellsand its mechanism].

Abstract: 

To investigate the effects of artesunate combined with bortezomib on the proliferation, apoptosis and autophagy of human acute myeloid leukemia cell lines MV4-11, and its mechanisms.MTT method was used to determine the anti-proliferation effect of different concentrations of artesunate, bortezomib and their combination on MV4-11 cells. The cell apoptosis were analyzed by flow cytometry. The expression of cleaved-Caspase-3, Bcl-2 family protein (Bcl-2, Mcl-1, Bim, Bax) and autophagy-related protein LC3B were assayed by Western blot.Artesunate displayed a proliferation inhibition effect on MV4-11 with dose- and time-dependent manner, the IC(50) of artesunate on MV4-11 after 48 hours was 1.44μg/ml. Bortezomib displayed a proliferation inhibition effect on MV4-11 with dose-dependent manner, the IC(50) of bortezomib on MV4-11 after 48 hours was 8.97 nmol/L. The combination of artesunate (0.75, 1.0 μg/ml) and Bortezomib (6, 8 nmol/L) showed higher inhibition on MV4-11 than artesunate orbortezomib alone in the same concentration gradient after 48 hours (

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PMID: 

Molecules. 2017 Mar 27 ;22(4). Epub 2017 Mar 27. PMID: 28346389

Abstract Title: 

Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro.

Abstract: 

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required.

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PMID: 

Exp Parasitol. 2015 Sep ;156:26-31. Epub 2015 May 27. PMID: 26024969

Abstract Title: 

Effects of artesunate against Trypanosma cruzi.

Abstract: 

Therapy against Trypanosma cruzi relies on only two chemically related nitro-derivative drugs, benznidazole and nifurtimox, both limited by poor efficacy and toxicity. It is suspected that with prolonged usage of these drugs, resistant parasites will be selected, which results in risk for treatment failure over the time. Herein, we studied the in vitro activity of artesunate, the most effective drug to treat severe P. falciparum and chloroquine-resistant P. vivax, on three strains of T. cruzi originated in different regions of Latin America (Argentina, Nicaragua and Brazil). The results of these assays showed that artesunate inhibits multiplication of epimastigotes (IC50 = 50, 6.10 and 23 µM, respectively) and intracellular amastigotes (IC50 = 15, 0.12 and 6.90 µM, respectively), indicating that it represents a potent anti-T. cruzi compound in terms of inhibiting parasite multiplication in vitro. We then tested the effect of artesunate in Balb/c mice infected with Brazil strain and found that it failed to cure the infection, suggesting that the drug may be unsuitable for in vivo treatment. When infected mice were treated with high doses AS + BZ, the outcome of infection was similar to that observed in mice treated with BZ alone. Nevertheless, understanding of structure-activity relationship of artesunate might lead to the development of new and effective drugs against T. cruzi.

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PMID: 

Arch Med Res. 2017 10 ;48(7):623-630. Epub 2018 Mar 12. PMID: 29544887

Abstract Title: 

Inhibitory Effect of Artesunate on Growth and Apoptosis of Gastric Cancer Cells.

Abstract: 

OBJECTIVE: The present study aimed to explore the inhibitory effect of artesunate on the growth and apoptosis of gastric cancer cells, in order to search for high effective and low toxic anti-gastric cancer drugs.METHODS: Flow cytometry was used to detect the CDC25A protein expression in different gastric diseases. After the treatment of different concentrations of artesunate (0, 30, 60, 120 μmol/l) on the gastric cancer cell line SGC-7901 cells for 24 h, 0 μmol/l Art was instead of normal saline as control group, the expression of CDC25A, Bcl-2, Bax, Caspase-3 protein, mitochondrial membrane potential, cell apoptosis and cell cycle were detected by flow cytometry.RESULTS: The CDC25A protein expression in gastric adenocarcinoma was significantly higher than that in normal gastric tissues. After the treatment of different concentrations of Art, the apoptosis rate of SGC-7901 cells in Art groups was significantly higher than that in control group. The proliferation index and CDC25A protein of SGC-7901 cells in Art groups was significantly lower than that in control group. Compared with control group, the Bcl-2 protein and mitochondrial membrane potential was significantly lower but the Bax and Caspase-3 protein expression level was significantly higher.CONCLUSIONS: The high expression of CDC25A protein in gastric adenocarcinoma is involved in the occurrence and development of gastric adenocarcinoma. Artesunate can inhibit the growth of gastric adenocarcinoma cells SGC-7901 and induce the cell apoptosis, the mechanism may be related to the regulation of CDC25A, Bcl-2, Bax, Caspase-3 and mitochondrial membrane potential in SGC-7901 cells.

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PMID: 

Molecules. 2017 Aug 8 ;22(8). Epub 2017 Aug 8. PMID: 28786914

Abstract Title: 

Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway.

Abstract: 

The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. Through Ingenuity Pathway Analysis, we discovered that the top-ranked ART-regulated biological pathways are abrogation of fatty acid biosynthetic pathway and mitochondrial dysfunction. Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. In addition, ART also regulates several proteins that are involved in NF-κB pathway, and our subsequent assays showed that ART suppresses the NF-κB pathway. These proteomic findings will contribute to improving our understanding of the underlying molecular mechanisms of ART for its therapeutic cytotoxic effect towards cancer cells.

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PMID: 

Zhonghua Xue Ye Xue Za Zhi. 2019 Jan 14 ;40(1):63-68. PMID: 30704231

Abstract Title: 

[Artesunate attenuate chronic graft-versus-host disease by regulating Th17/Treg balance].

Abstract: 

To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD).Recipient BALB/c mice received 8× 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry.Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)%(55.71±6.99)%,(2)=5.457,=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)%(8.40±0.23)%,=15.679,

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PMID: 

Biomed Pharmacother. 2019 Jan ;109:2043-2053. Epub 2018 Nov 26. PMID: 30551460

Abstract Title: 

Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway.

Abstract: 

Liver fibrosis is a progression of chronic liver disease, which lacks effective therapies in the world. Attractively, more and more evidences show that natural products are safe and effective in the prevention and treatment of hepatic fibrosis. Artesunate, a water-soluble hemisuccinate derivative of artemisinin, exerts various pharmacological activities such as anti-inflammatory, anti-tumor and immunomodulating abilities. However, the effects of artesunate on hepatic fibrosis are little-known. Here our study was performed to investigate the effect of artesunate on carbon tetrachloride (CCl)-induced mouse liver fibrosis and elucidate whether artesunate could alleviate liver fibrosis by regulating ferritinophagy- mediated ferroptosis in hepatic stellate cells (HSCs). Firstly, our results demonstrated that artesunate treatment could induce activated HSC ferroptosis in fibrotic livers. Moreover, primary HSCs isolated from different animal groups were cultured to detect biomarkers of ferroptosis including iron, lipid peroxidation, glutathione (GSH) and prostaglandin endoperoxide synthase 2 (ptgs2) levels. The results revealed that artesunate remarkably promoted ferroptosis of activated HSCs. Furthermore, consistent with the experimental results in vivo, the data in vitro still indicated that artesunate treatment markedly induced ferroptosis in activated HSCs, which mainly embodied as declined cell vitality, increased cell death rate, accumulated iron, elevated lipid peroxides and reduced antioxidant capacity. Conversely, inhibition of ferroptosis by deferoxamine (DFO) completely abolished artesunate-induced anti-fibrosis effect. Surprisingly, artesunate also evidently triggered ferritinophagy accompanied by up-regulation of LC3 (microtubule-associated protein light chain 3), Atg3, Atg5, Atg6/beclin1, Atg12 (autophagy related genes) and down-regulation of p62, FTH1 (ferritin heavy chain), NCOA4 (nuclear receptor co-activator 4) in activated HSCs. Nevertheless, depletion of ferritinophagy by specific inhibitor lysosomal lumen alkalizer-chloroquine (CQ) inhibited artesunate-induced ferroptosis and anti-fibrosis function. These results suggested that ferritinophagy-mediated HSC ferroptosis was responsible for artesunate-induced anti-fibrosis efficacy, which provided new clues for further pharmacological study of artesunate.

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PMID: 

Biomed Res Int. 2016 ;2016:1489050. Epub 2016 Dec 27. PMID: 28116289

Abstract Title: 

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases.

Abstract: 

Artesunate is an important agent for cerebral malaria and all kinds of other severe malaria because it is highly efficient, lowly toxic, and well-tolerated. Loads of research pointed out that it had widespread pharmacological activities such as antiparasites, antitumor, anti-inflammation, antimicrobes activities. As we know, the occurrence and development of neurological disorders usually refer to intricate pathophysiologic mechanisms and multiple etiopathogenesis. Recent progress has also demonstrated that drugs with single mechanism and serious side-effects are not likely the candidates for treatment of the neurological disorders. Therefore, the pluripotent action of artesunate may result in it playing an important role in the prevention and treatment of these neurological disorders. This review provides an overview of primary pharmacological mechanism of artesunate and its potential therapeutic effects on neurological disorders. Meanwhile, we also briefly summarize the primary mechanisms of artemisinin and its derivatives. We hope that, with the evidence presented in this review, the effect of artesunate in prevention and curing for neurological disorders can be further explored and studied in the foreseeable future.

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PMID: 

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2014 ;31(9):1616-24. Epub 2014 Aug 18. PMID: 25068920

Abstract Title: 

Effects of microwave heating on the migration of substances from melamine formaldehyde tableware.

Abstract: 

Melamine formaldehyde (MF) tableware, after undergoing repeated heating in a microwave oven for 1, 2, 3 or 5 min, was tested for migration into 3% (w/v) acetic acid, a food simulant. Overall migration (OM) consistently increased with an increasing number of heating/washing cycles, while formaldehyde was found at low concentrations or was not detectable. Unexpectedly, the 1-min series caused the most rapid increase in OM; the European Union regulatory limit of 10 mg dm(-2) was exceeded after 25 cycles. The number of cycles required to reach the OM limit rose to 29 and 67 for the 2- and 3-min series, respectively. Only 37 cycles were needed in the case of the 5-min series; however, the cumulative exposure time to microwave irradiation was relatively close to that of the 3-min series. These findings indicate that microwave heating affects the migration of MF in a significantly different manner as compared with conventional heating reported in previous studies. Fourier transform infrared spectroscopy (FTIR) spectra of MF after completing the microwave heating series show that the plastic was not fully cured, as evidenced by the absence of methylene linkages. The majority of migrants obtained from OM tests consisted of low molecular weight methylol melamine derivatives. The results indicate that microwave heating allowed demethylolation, addition and condensation reactions to occur, which was not the case when using conventional heating. This study demonstrates that microwave heating for 1-2 min in a repeated manner is of high concern in terms of consumer health. It was found that the service terms of melamine ware under microwave heating were drastically reduced, by more than 10-fold, as compared with the service terms under conventional heating. Hence, it is strongly recommended that manufacturers of MF articles provide instructions for use, e.g."Do not use in microwave", which should be clearly visible to consumers and not easily detachable.

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PMID: 

Biomed Res Int. 2015 ;2015:603260. Epub 2015 Feb 1. PMID: 25705676

Abstract Title: 

Estimation of radiofrequency power leakage from microwave ovens for dosimetric assessment at nonionizing radiation exposure levels.

Abstract: 

The electromagnetic field leakage levels of nonionizing radiation from a microwave oven have been estimated within a complex indoor scenario. By employing a hybrid simulation technique, based on coupling full wave simulation with an in-house developed deterministic 3D ray launching code, estimations of the observed electric field values can be obtained for the complete indoor scenario. The microwave oven can be modeled as a time- and frequency-dependent radiating source, in which leakage, basically from the microwave oven door, is propagated along the complete indoor scenario interacting with all of the elements present in it. This method can be of aid in order to assess the impact of such devices on expected exposure levels, allowing adequate minimization strategies such as optimal location to be applied.

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