Artemisinin

Jpn J Infect Dis. 2015;68(4):321-3.

Impact of Artemisinin-based Combination Therapy on falciparum malaria in urban Kolkata: a clinic based report.[Pubmed: 25720645]

In India, Artemisinin-based combination therapy (ACT; specifically artesunate + sulfadoxine-pyrimethamine) has been implemented for uncomplicated falciparum malaria since 2010. But for vivax malaria drug policy remained unchanged i.e., chloroqine and primaquine.
METHODS AND RESULTS:
We observed the impact of this intervention in urban Kolkata by analyzing data from the Malaria Clinic from 2001 to 2013. In Kolkata, we observed that Plasmodium vivax was perennial, whereas P. falciparum infection was seasonal. Before ACT implementation, the proportion of P. falciparum was as high as 50% and it steadily decreased during 4 successive years post intervention. No change was observed in the number of P. vivax cases.
CONCLUSIONS:
ACT may be an effective measure in reducing falciparum malaria cases. Artemisinin-derivative combination therapies should be explored in vivax malaria to reduce the overall burden of malaria.

Current Science, 2000 , 78 (6) :709-713.

Antimicrobial activity of artemisinin and its precursors.[Reference: WebLink]

Artemisinic acid and Arteannuin B are biogenetic precursors of Artemisinin, an important antimalarial produced by the herb Artemisia annua. These compounds have been screened for antimicrobial activity against a range of organisms.
CONCLUSIONS:
All the three compounds are active against different bacteria and certain fungal species.

Redox Biol . 2017 Aug;12:625-633.

Artemisinin protects PC12 cells against β-amyloid-induced apoptosis through activation of the ERK1/2 signaling pathway[Pubmed: 28391183]

Abstract Accumulating evidence displays that an abnormal deposition of amyloid beta-peptide (Aβ) is the primary cause of the pathogenesis of Alzheimer's disease (AD). And therefore the elimination of Aβ is regarded as an important strategy for AD treatment. The discovery of drug candidates using culture neuronal cells against Aβ peptide toxicity is believed to be an effective approach to develop drug for the treatment of AD patients. We have previously showed that Artemisinin, a FDA-approved anti-malaria drug, has neuroprotective effects recently. In the present study, we aimed to investigate the effects and potential mechanism of Artemisinin in protecting neuronal PC12 cells from toxicity of β amyloid peptide. Our studies revealed that Artemisinin, in clinical relevant concentration, protected and rescued PC12 cells from Aβ25-35-induced cell death. Further study showed that Artemisinin significantly ameliorated cell death due to Aβ25-35 insult by restoring abnormal changes in nuclear morphology, lactate dehydrogenase, intracellular ROS, mitochondrial membrane potential and activity of apoptotic caspase. Western blotting analysis demonstrated that Artemisinin activated extracellular regulated kinase ERK1/2 but not Akt survival signaling. Consistent with the role of ERK1/2, preincubation of cells with ERK1/2 pathway inhibitor PD98059 blocked the effect of Artemisinin while PI3K inhibitor LY294002 has no effect. Moreover, Aβ1-42 also caused cells death of PC12 cells while Artemisinin suppressed Aβ1-42 cytotoxicity in PC12 cells. Taken together, these results, at the first time, suggest that Artemisinin is a potential protectant against β amyloid insult through activation of the ERK1/2 pathway. Our finding provides a potential application of Artemisinin in prevention and treatment of AD. Keywords: Alzheimer's disease; Artemisinin; Aβ25–35; ERK1/2; PC12 cells.

Front Cell Neurosci . 2018 Apr 20;12:108.

Artemisinin Prevents Glutamate-Induced Neuronal Cell Death Via Akt Pathway Activation[Pubmed: 29731711]

Abstract Artemisinin is an anti-malarial drug that has been in use for almost half century. Recently, novel biological effects of Artemisinin on cancer, inflammation-related disorders and cardiovascular disease were reported. However, neuroprotective actions of Artemisinin against glutamate-induced oxidative stress have not been investigated. In the current study, we determined the effect of Artemisinin against oxidative insult in HT-22 mouse hippocampal cell line. We found that pretreatment of Artemisinin declined reactive oxygen species (ROS) production, attenuated the collapse of mitochondrial membrane potential induced by glutamate and rescued HT-22 cells from glutamate-induced cell death. Furthermore, our study demonstrated that Artemisinin activated Akt/Bcl-2 signaling and that neuroprotective effect of Artemisinin was blocked by Akt-specific inhibitor, MK2206. Taken together, our study indicated that Artemisinin prevented neuronal HT-22 cell from glutamate-induced oxidative injury by activation of Akt signaling pathway. Keywords: Akt; apoptosis; Artemisinin; neuroprotection; oxidative stress.

Mutat Res Genet Toxicol Environ Mutagen. 2015 Jan 1;777:1-6.

The antimalarial agent artesunate causes sperm DNA damage and hepatic antioxidant defense in mice.[Pubmed: 25726169]

Artesunate is an Artemisinin derivative effective against multidrug resistant malaria.
METHODS AND RESULTS:
We analyzed the effects of artesunate 40 mg/kg b.w. as a single dose (ART1) or 13.3mg/kg b.w. for 3 days at 24h intervals (ART2) on mice spermatozoa at morphological and molecular level, and hepatic antioxidant status following 24h and 35 days following exposures in vivo. Artesunate significantly reduced epididymal sperm count and increased the frequency of sperms with abnormal head morphology following 24h of exposure. Comet assay analysis revealed significant increase in DNA strand breaks in spermatozoa evidenced by about 3-fold increase in comet tail DNA and up to 10-fold increase in Olive tail moment following 35 days of artesunate treatment. The damage index was significantly higher in the treated groups (40.27 ± 6.62 and 37.07 ± 5.35 for ART1 and ART2 respectively) as compared to the control group (16.13 ± 3.21) indicating the genotoxic effect of artesunate. The significant reduction in GSH, SOD and increase in lipid peroxidation indicate involvement of oxidative mechanisms in artesunate induced toxicity in mice.
CONCLUSIONS:
The present study suggests that artesunate has the potential to breach the testis-blood barrier and cause toxicity to male germ cells which may have implications in male reproductive toxicity.

Clin Exp Pharmacol Physiol. 2015 Feb 24.

Artemisinin inhibits tumor necrosis factor-α-induced vascular smooth muscle cell proliferation in vitro and attenuates balloon injury-induced neointima formation in rats.[Pubmed: 25707499]

The aim of this study was to evaluate the effect of Artemisinin (ART) on rat vascular smooth muscle cell (VSMC) proliferation induced by tumour necrosis factor (TNF)-α, cell cycle arrest, and apoptosis, and its effect on neointima formation after balloon injury of rat carotid artery.
METHODS AND RESULTS:
Primary rat VSMC were identified by immunofluorescence assay. The proliferation of VSMC induced by TNF-α was significantly inhibited by ART treatment in a dose-dependent manner. Treatment with 100-μM ART significantly reduced the expression of proliferating cell nuclear antigen. In contrast, the same treatment arrested the cell cycle in G0/G1 phase. Western blot analysis showed that the cell cycle-related proteins cyclin D1, cyclin E, cyclin-dependent kinase 2, and cyclin-dependent kinase 4 were downregulated by ART in TNF-α-stimulated VSMC. For apoptosis induced by ART, cleaved caspase-3/-9 was detected, and the pro-apoptotic protein Bcl-2-associated X protein was upregulated while the anti-apoptotic protein Bcl-2 was downregulated.
CONCLUSIONS:
The results suggest that ART can effectively inhibit the proliferation of VSMC induced by TNF-α through the apoptotic induction pathway and cell cycle arrest. Also, balloon injury indicated that ART significantly inhibited neointima formation in the rat carotid arteries.