Phytochemical Profiles and Neuroprotective, Anti-epileptogenic Activities of Artemisia glauca and Artemisia vulgaris from Kazakhstan.

Collaborative Research Program 2023-2025

Epilepsy is a common chronic neuronal disorder due to either genetically determined or acquired brain abnormalities. Epilepsy is clinically manifested by periodic, unpredictable, and recurrent seizures that have a great clinical relevance due to their prevalence and severity, and pathologically, characterized by brain damage associated with neuronal loss and gliosis. In addition, cognitive abnormality, especially the impairment in learning/memory, is one of the serious comorbidities of the disease that has a significant negative impact on patients’ quality of life. However, there is no cure for epilepsy because the underlying mechanisms of epilepsy itself and the cognitive abnormality accompanied by epilepsy are still unclear.
Currently available antiepileptic drugs (AEDs) are only partially (~30%) efficient for epilepsy. Although AEDs control nearly 70% of patients with epilepsy, 5-10% of patients still require additional medications and more than 20% of patients continue to have seizures after treatment. They can only treat the symptoms of epilepsy without making any significant progress in neither reversing its underlying mechanisms nor offering neuroprotection caused by the pathogenesis of epilepsy, resulting in about 15-40% of all patients with epilepsy, unfortunately, continue to have seizures that impair their daily living. Moreover, most AEDs have shown cognitive, psychiatric, and behavioral side effects on patients. Thus, the need for medical care for patients with uncontrolled epilepsy remains unmet and the development of alternative, more effective but with fewer side effects and clinically relevant novel therapeutic approaches for epilepsy are in urgent demand. Growing evidence shows that the neuronal damage and death caused by seizure-associated neuronal excitability/excitotoxicity, accompanied by neuroinflammation and ROS accumulation in the brain, are most likely responsible for sustained epilepsy and epilepsy-induced cognitive impairment. Thus, the focus of epilepsy research and treatment strategy has shifted to reducing or eliminating neuroinflammation and oxidative damage through alternative approaches, such as herbal plants, with better efficacy and minimal side effects. Furthermore, it is postulated that the use of plant-based antioxidant and anti-inflammatory compounds such as flavonoids and coumarins could be a desirable strategy in the treatment of chronic epilepsy and epilepsy-/AEDs-related comorbidities. The Artemisia glauca and Artemisia vulgaris are the genus Artemisia plants growing wild over Central Asia and Kazakhstan and are widely used in folk medicine for the treatment of different ailments. Phytochemical studies revealed that these Artemisia species contain a high concentration of flavonoids (Artemisia vulgaris) and coumarins (Artemisia glauca) and show promising antioxidant activities in our preliminary pharmacological studies. Therefore, the purpose of this project is to investigate the anticonvulsant and neuroprotective activities of Artemisia glauca and Artemisia vulgaris and their relationship to oxidative stress and neuroinflammation by using a well-established acoustically evoked seizures model of genetically epilepsy-prone rats (GEPR-3s). Further, based on the results of the bioassay, identify and isolate biologically active constituents of the plant extracts, and finally determine their chemical structures.