Repurposing artemisinins as neuroprotective agents: a focus on the PI3k/Akt signalling pathway

Arthur, Richmond; Navik, Umashanker; Kumar, Puneet

doi:10.1007/s00210-022-02350-z

Cited by 7 publications

(4 citation statements)

References 92 publications

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“…Although this study is, to the best of our knowledge, the first to investigate whether AR has a therapeutic effect on PTSD-like symptoms, a large body of literature has reported that AR improves synaptic plasticity and attenuates neuronal apoptosis in models of multiple neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and multiple sclerosis ( Zhao et al, 2020 ; Arthur et al, 2023 ). Poorgholam et al found that artemisinin improved synaptic plasticity in rat models of Alzheimer’s disease and diabetes ( Poorgholam et al, 2023 ), while Xia et al observed that administering Dihydroartemisinin could have a therapeutic effect on impaired synaptic plasticity caused by tauopathies ( Xia et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Artemisinin (AR) is a natural compound obtained from the Artemisia annua plant. Although AR is most renowned for its potent anti-malarial properties ( Ma et al, 2020 ), recent findings suggest that it exerts neuroprotective effects ( Kshirsagar and Rao, 2021 ; Arthur et al, 2023 ). Specifically, it may alleviate oxidative stress, inhibit neuroapoptosis, suppress neuroinflammation, and promote synaptic plasticity in the contexts of multiple neurological conditions, including stroke, Alzheimer’s disease, Parkinson’s disease, and depression ( He et al, 2021 ; Yan et al, 2021 ; Peng et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress

Liu,

Ding,

Wang

et al. 2024

Front. Pharmacol.

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Post-Traumatic Stress Disorder (PTSD) is a chronic mental disorder characterized by symptoms of panic and anxiety, depression, impaired cognitive functioning, and difficulty in social interactions. While the effect of the traditional Chinese medicine artemisinin (AR) on PTSD is unknown, its therapeutic benefits have been demonstrated by studies on models of multiple neurological disorders. This study aimed to extend such findings by investigating the effects of AR administration on a rat model of PTSD induced by a regimen of single prolonged stress (SPS). After rats were subjected to the SPS protocol, AR was administered and its impact on PTSD-like behaviors was evaluated. In the present study, rats were subjected to a multitude of behavioral tests to evaluate behaviors related to anxiety, memory function, and social interactions. The expression of hippocampal synaptic plasticity-related proteins was detected using Western blot and immunofluorescence. The ultrastructure of synapses was observed under transmission electron microscopy. The apoptosis of hippocampal neurons was examined with Western blot, TUNEL staining, and HE staining. The results showed that AR administration alleviated the PTSD-like phenotypes in SPS rats, including behavior indicative of anxiety, cognitive deficits, and diminished sociability. AR administration was further observed to improve synaptic plasticity and inhibit neuronal apoptosis in SPS rats. These findings suggest that administering AR after the onset of severe traumatic events may alleviate anxiety, cognitive deficits, and impaired social interaction, improve synaptic plasticity, and diminish neuronal apoptosis. Hence, the present study provides evidence for AR’s potential as a multi-target agent in the treatment of PTSD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress

Liu,

Ding,

Wang

et al. 2024

Front. Pharmacol.

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“…Upon inhibiting ERK1/2, the protective effect of artemisinin against cell viability loss, intracellular ROS accumulation, mitochondrial membrane potential decrease, cell apoptosis in vitro, and behavioral deficits and brain pathological damage in vivo were significantly attenuated. In addition, studies have shown that the role of the Transcription Factor EB (TFEB) signaling pathway and the PI3K/Akt signaling pathway in PD is also worthy of attention [ 40 , 41 ]. The TFEB signaling pathway plays a key role in regulating autophagy function, while the PI3K/Akt signaling pathway mediates various biological functions, including inflammation, autophagy, oxidative stress, etc.…”

Section: Discussionmentioning

confidence: 99%

Artemisinin Confers Neuroprotection against 6-OHDA-Induced Neuronal Injury In Vitro and In Vivo through Activation of the ERK1/2 Pathway

Li,

Fang

et al. 2023

Molecules

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Parkinson’s disease (PD) is an age-related, progressive neurodegenerative disease characterized by the gradual and massive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). We have recently reported that artemisinin, an FDA-approved first-line antimalarial drug, possesses a neuroprotective effect. However, the effects and underlying mechanisms of artemisinin on Parkinson’s disease remain to be elucidated. In this study, we investigated the neuroprotective effects of artemisinin on 6-OHDA and MPP+ in neuronal cells and animal models, as well as the underlying mechanisms. Our results showed that artemisinin significantly attenuated the loss of cell viability, LDH release, elevated levels of reactive oxygen species (ROS), the collapse of the mitochondria trans-membrane potential and cell apoptosis in PC12 cells. Western blot results showed that artemisinin stimulated the phosphorylation of ERK1/2, its upstream signaling proteins c-Raf and MEK and its downstream target CREB in PC12 cells in a time- and concentration-dependent manner. In addition, the protective effect of artemisinin was significantly reduced when the ERK pathway was blocked using the ERK pathway inhibitor PD98059 or when the expression of ERK was knocked down using sgRNA. These results indicate the essential role of ERK in the protective effect of artemisinin. Similar results were obtained in SH-SY5Y cells and primary cultured neurons treated with 6-OHDA, as well as in cellular models of MPP+ injury. More interestingly, artemisinin attenuated PD-like behavior deficit in mice injected with 6-OHDA evaluated by behavioral tests including swimming test, pole-test, open field exploration and rotarod tests. Moreover, artemisinin also stimulated the phosphorylation of ERK1/2, inhibited apoptosis, and rescued dopaminergic neurons in SNc of these animals. Application of ERK pathway inhibitor PD98059 blocked the protective effect of artemisinin in mice during testing. Taking these results together, it was indicated that artemisinin preserves neuroprotective effects against 6-OHDA and MPP+ induced injury both in vitro and in vivo by the stimulation of the ERK1/2 signaling pathway. Our findings support the potential therapeutic effect of artemisinin in the prevention and treatment of Parkinson’s disease.

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“…Post-CM, developmental, cognitive, and behavioral deficits in sub-Saharan Africa can persist for up to a year contributed by factors like HIV co-infection, stature, and MRI abnormalities which are a significant burden on families and communities due to limited resources for treatment, education, and rehabilitation ( Langfitt et al, 2019 ). Children under the age of five, who account for 67% of all fatalities worldwide, bear the greatest burden of severe malaria ( Varo et al, 2020 ) including the rising resistance to insecticides and antimalarials ( Wicht et al, 2020 ; Shahbodaghi and Rathjen, 2022 ; Suh et al, 2023 ) and mental health risks leading to neurological impairment ( Goyal et al, 2023 ), necessitate a comprehensive malaria elimination program involving vector control ( Ogunah et al, 2020 ), chemoprevention, vaccination, improved and early diagnosis accuracy ( Pradhan et al, 2019 ), neuroprotective agents ( Arthur et al, 2022 ), neurorehabilitation ( Boubour et al, 2020 ) and regionally tailored strategies to address mental health consequences.…”

Section: Introductionmentioning

confidence: 99%

Exploring the hidden mental health consequences of malaria beyond the fever

Nandish,

B. M.,

et al. 2024

Front. Hum. Neurosci.

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Malaria morbidity has various presentations and the focus now shifts to uncommon signs and symptoms of malaria infection such as cognitive impairment to address the morbidity when the mortality declines. About 50% of children admitted to hospitals due to malaria experience neurological complications due to factors like low blood sugar, inflammation, elevated pressure, decreased oxygen levels, and excitotoxicity. Malaria during pregnancy negatively also impacts children’s cognitive, behavioral, and executive function leading to neurodevelopmental delay due to increased susceptibility which can significantly affect maternal and child health, leading to higher rates of underestimated factors like anxiety, depression, and PTSD. Despite having the world’s second-largest tribal population, India’s indigenous and tribal communities and their mental health are less explored and less understood. Western psychological tools and neurocognitive assessment tools are not universally applicable, thus necessitating the development of tailored tools to investigate psychological or neurocognitive impairment. This paper has illuminated the hidden mental health consequences of malaria infection, emphasizing the prevalence, nature, and implications of psychological distress among affected individuals. The findings underscore the importance of recognizing and addressing these psychological consequences in the holistic management and prevention of malaria and its mental health consequences.

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Repurposing artemisinins as neuroprotective agents: a focus on the PI3k/Akt signalling pathway

Cited by 7 publications

References 92 publications

Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress

Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress

Artemisinin Confers Neuroprotection against 6-OHDA-Induced Neuronal Injury In Vitro and In Vivo through Activation of the ERK1/2 Pathway

Exploring the hidden mental health consequences of malaria beyond the fever

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