Artemisinin and its derivatives in treating helminthic infections beyond schistosomiasis

Lam, Nelson Siukei; Long, Xin-Xin; Su, Xin-zhuan; Lü, Fangli

doi:10.1016/j.phrs.2018.04.025

Cited by 39 publications

(19 citation statements)

References 145 publications

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“…In this regard, terpene/terpenoid phytochemicals have previously been explored and repurposed for their synergistic anti-parasitic capabilities; a well-known example is artemisinin, an endo-peroxide containing sesquiterpenoid lactone derived from Artemisia annua . Originally reported to inhibit Plasmodium proliferation ( Su and Miller, 2015 ), artemisinin has subsequently been shown to affect other parasitic protozoan and helminth species ( Loo et al, 2017 ; Lam et al, 2018 ). Of interest to the current study, in vitro cultivated F. hepatica and S. mansoni are both susceptible to artemisinin-based chemotherapies ( Keiser and Utzinger, 2007 ).…”

Section: Resultsmentioning

confidence: 99%

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Whiteland

Chakroborty

Forde-Thomas

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature flukes, 2 for mature flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis.

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Section: Resultsmentioning

confidence: 99%

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Whiteland

Chakroborty

Forde-Thomas

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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“…DHA, the active metabolite of artemisinin, may meet the conditions for the induction of basal autophagy and correction of autophagic flux (Ho et al, 2014;Efferth, 2017;Lam et al, 2018). However, no study has mentioned the therapeutic effect of DHA in AD regarding the degradation of toxic aggregated proteins by inducing autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, Chinese herbal medicine has received great attention in maintaining the efficient flux of autophagy in the brain. Artemisinins, a class of sesquiterpene trioxane lactone agents extracted from the ancient Chinese herb Artemisia annua L, has been used effectively to treat malaria (Lam et al, 2018) with universally acknowledged safety records in clinical trials (Kloprogge et al, 2018;Lohy Das et al, 2018). The main mechanism by which artemisinin acts in the treatment of malaria is activating autophagy to change the membrane structure of the parasite and, subsequently, starving the parasite (Chen et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin Ameliorates Learning and Memory in Alzheimer’s Disease Through Promoting Autophagosome-Lysosome Fusion and Autolysosomal Degradation for Aβ Clearance

Zhao

Long

Ding

et al. 2020

Front. Aging Neurosci.

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Dihydroartemisinin (DHA) is an active metabolite of sesquiterpene trioxane lactone extracted from Artemisia annua, which is used to treat malaria worldwide. DHA can activate autophagy, which is the main mechanism to remove the damaged cell components and recover the harmful or useless substances from eukaryotic cells and maintain cell viability through the autophagy lysosomal degradation system. Autophagy activation and autophagy flux correction are playing an important neuroprotective role in the central nervous system, as they accelerate the removal of toxic protein aggregates intracellularly and extracellularly to prevent neurodegenerative processes, such as Alzheimer's disease (AD). In this study, we explored whether this mechanism can mediate the neuroprotective effect of DHA on the AD model in vitro and in vivo. Three months of DHA treatment improved the memory and cognitive impairment, reduced the deposition of amyloid β plaque, reduced the levels of Aβ40 and Aβ42, and ameliorated excessive neuron apoptosis in APP/PS1 mice brain. In addition, DHA treatment increased the level of LC3 II/I and decreased the expression of p62. After Bafilomycin A1 and Chloroquine (CQ) blocked the fusion of autophagy and lysosome, as well as the degradation of autolysosomes (ALs), DHA treatment increased the level of

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“…Many other helminthic infections were tested with artemisinin and its derivatives including cestode infections (Echinococcus spp., Taenia crassiceps) and other trematodes infections (Echinostoma spp., Fasciola spp., Clonorchis sinensis, Opisthorchis viverrini, Paragonimus westermani, Heterophyes heterophyes, and Paramphistomum microbothrium) [263].…”

Section: Anti-helminthic Activitiesmentioning

confidence: 99%

Artemisia annua, a Traditional Plant Brought to Light

Septembre-Malaterre

Rakoto

Marodon³

et al. 2020

IJMS

104

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Traditional remedies have been used for thousand years for the prevention and treatment of infectious diseases, particularly in developing countries. Of growing interest, the plant Artemisia annua, known for its malarial properties, has been studied for its numerous biological activities including metabolic, anti-tumor, anti-microbial and immunomodulatory properties. Artemisia annua is very rich in secondary metabolites such as monoterpenes, sesquiterpenes and phenolic compounds, of which the biological properties have been extensively studied. The purpose of this review is to gather and describe the data concerning the main chemical components produced by Artemisia annua and to describe the state of the art about the biological activities reported for this plant and its compounds beyond malaria.

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Artemisinin and its derivatives in treating helminthic infections beyond schistosomiasis

Cited by 39 publications

References 145 publications

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Dihydroartemisinin Ameliorates Learning and Memory in Alzheimer’s Disease Through Promoting Autophagosome-Lysosome Fusion and Autolysosomal Degradation for Aβ Clearance

Artemisia annua, a Traditional Plant Brought to Light

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