## 1 Introduction  
Oxidative stress (OS) plays a pivotal role in the onset of numerous neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS) [1]. Proteins and lipids in cells, as well as other cellular macromolecules, can be damaged as a result of the induction of OS, which is caused by an imbalance between the total oxidant status (TOS) and the total antioxidant status (TAS) [2,3]. Protein thiol groups undergo oxidation during OS, resulting in the formation of disulfide bonds. Thiol/disulfide homeostasis (TDH) between thiols and disulfide bonds is maintained due to disulfide bonds being re-reduced to thiol groups [4]. Malondialdehydedehyde (MDA) and lipid peroxides are generated from the lipid oxidation/peroxidation as a result of OS [5]. High-density lipoprotein (HDL) cholesterol, as well as oxidized low-density lipoproteins (oxLDL), contain lipid peroxides that paraoxonase-1 (PON1) hydrolyzes in order to avoid lipoprotein oxidation [6]. OS can lead to post-translational modifications of proteins, influencing the activity of certain transcription factors. When oxidative stress modifies the Kelch-like enoyl-CoA hydratase-associated protein 1 (KEAP1), it results in the activation of the Nuclear factor-erythroid 2-related factor 2 (NRF2). NRF2 then binds to the antioxidant-response element (ARE) and translocates to the nucleus. Inside the nucleus, NRF2 triggers the transcription of various antioxidant enzyme genes and proteins, such as catalase (CAT), glutamate-cysteine ligase catalytic (GCLC), glutathione peroxidase (GPx), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase (SOD) [7].  
Due to their high morbidity and death rates, NDs are becoming more common, which has a significant impact. Unfortunately, existing treatment options provide only temporary benefits and limited symptomatic relief [8]. OS has long been linked to NDs, either as a direct cause or as a result of other variables' downstream effects. Thus, targeting OS in the central neural cells with antioxidants is arguably a potential alternative to the available treatment options for NDs. Significant study has been conducted in the last decade to find ways of utilizing natural plant antioxidants to fight OS [9]. _Glaucium grandiforum_ Boiss. and A. Huet subsp. _refractum_ (Nabelek) [PERSON], a member of the Papaveraceae family from the _Glaucium_ genus, is also recognized by names such as Bristly horned-poppy, red horned-poppy, and blackspot hornpoppy [10]. It contains various isoquinoline alkaloids, including allocryptopine, tetrahydropalmatine, and tetrahydroroberberine N-oxide (trans-cannadine-N-oxide), which are renowned for their antioxidant capabilities [11; 12; 13]. Historically, extracts from _G. grandiforum_ have been utilized in treatments related to brain conditions such as memory impairment [14; 15]. Additionally, these extracts display anti-acetylcholinesterasees (AChE), antibutrylcholinesterasees (BChE), and antigenotoxic properties [16; 17; 18; 19; 20; 21; 22]. Other studies have also explored the antibacterial, antimicrobial, and wound-healing potential of _G. grandiforum_ extracts [10; 23; 24]. Building on our prior research, we found that _G. grandiforum_ alkaloid extracts, which are rich in isoquinoline alkaloids, offer neuroprotection by minimizing intracellular reactive oxygen species (ROS) induced by hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) [12]. However, previous research has not examined the antioxidative effects of _G. grandiforum_'s chloroform, methanol, and water alkaloid extracts, which are abundant in isoquinoline alkaloids, against OS triggered by H\({}_{2}\)O\({}_{2}\). Therefore, our study aims to delve into the antioxidative potential of _G. grandiforum_'s isoquinoline alkaloid-rich extracts across different targets and potential mechanisms.