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As the primary bioactive compound of glycyrrhiza rhizome, the triterpene glycoside conjugate Glycyrrhizic acid (GA) has demonstrated neuroprotective effects in vivo. This study evaluates the effectiveness of GA as an inhibitor of GuHCl-induced amyloid aggregation of hen egg white lysozyme (HEWL). Fibril formation as measured by Thioflavin-T fluorescence, 900 light scattering, and 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence illustrated ∼90 % prevention of fibrils at [GA]/[HEWL] ≥2:1. Images of Transmission electron microscopy evidence for the absence of any fibril or amorphous aggregation products. The spectral characteristics of soluble HEWL were in close resemblance to unfolded monomer. Computational and fluorescence investigations performed to analyse GA-HEWL interactions demonstrated slightly higher affinity of GA to unfolded HEWL and aggregation-prone regions. The likely mechanism of monomer level aggregation prevention by GA as dermined by computational, stability, and ANS experiments illustrated that GA modulated the compactness, solvent-accessible surface, and solvent-exposed hydrophobic surfaces of aggregation-prone state of HEWL. Our findings corroborate GA as an effective inhibitor of HEWL amyloid formation. To our knowledge, GA interaction-induced inhibition of aggregation-prone states has not been previously discussed. GA's modulation of aggregation-prone states of disease-related proteins will successfully develop GA as an amyloid inhibitor for clinical trials of amyloidosis and neurodegenerative illnesses. • Glycyrrhizic acid (GA) is a molecule found inmglycyrrhiza rhizome (Mulethi) and shows neuroprotective activity. • GA binds to the monomeric aggregation precursor state of lysozyme and completely prevents its fibrillation. • GA prevents aggregation by masking the aggregation-prone surfaces. • GA may be developed into a new drug for treatment of lysozyme amyloidosis. [ABSTRACT FROM AUTHOR]

Ropinirole (ROP) is a dopamine agonist that can cross the blood-brain barrier (BBB), which is crucial for drugs targeting neurological conditions like Alzheimer's disease (AD). The rationale for the current research is to investigate the potential of ROP as an inhibitor of Microtubule affinity regulating kinase 4 (MARK4)-NFκβ in neurodegenerative diseases, specifically AD. The interaction between ROP and MARK4-NFκβ holds significant promise in the realm of drug discovery and therapeutic interventions for diseases like AD. Molecular docking and biophysical characterization demonstrate how ROP effectively hinders MARK4 activity, offering detailed insights into their molecular interactions. The present research also investigates the biological aspect of MARK4 shows promise in treating AD, with neuroinflammation playing a crucial role in the disease's progression. Aβ 42 and ROP were co-administered directly into the cells for the establishment of the AD model. We confirmed that ROP can inhibit the path of MARK4 activity, as evidenced by biophysical characterization, and can enhance the cell viability, lowers the expression of MARK4, decrease the rate of oxidative stress, and attenuate the expression of NFκβ, leading to reduced neuronal apoptosis in an in vitro -induced Aβ model. Overall, this research provides valuable mechanistic insights into the neuroprotective potential of ROP and its ability to target the MARK4-NFκβ pathway. The amyloid hypothesis (AH) suggests that Alzheimer's disease (AD) begins with the breakdown of amyloid precursor protein (APP) by β-secretase (BACE1), forming APP carboxyl-terminal fragments (CTFs). Subsequent processing by γ-secretase produces Aβ, leading to the formation of senile plaques in the extracellular space involving proteoglycans and apolipoproteins. Extracellular Aβ oligomers can trigger caspases via cell surface receptors, while intracellularly, Aβ may activate caspases through endoplasmic reticulum or mitochondrial stress. Immune response dysregulation can harm cells at a molecular level, releasing inflammatory markers and reactive oxygen species, culminating in cell death and plaque development in AD. The NFκβ and MARK4 pathway is highlighted as a key contributor to AD pathogenesis. [Display omitted] • Biophysical/kinetic confirming that ROP has inhibitory potential in the path of MARK4 activity. • The neuroprotective efficacy of ROP against the Aβ 42 model by enhancing cell viability • Lowering the expression of MARK4 can reduce oxidative stress and neuronal apoptosis by attenuating the NF-κB pathway. • The findings suggest that MARK4 inhibition can be a potential therapeutic approach for managing MARK4-associated diseases [ABSTRACT FROM AUTHOR]

The research presented aims at developing Ropinirole hydrochloride (RHCl) nanoemulsion (NE) with nigella oil for Parkinson's disease (PD). In silico study was done to explore interactions of ropinirole and thymoquinone at receptor site (TNF-α and NFK-β). Ropinirole and Thymoquinone forms a hydrogen bond with residue Arginine 201 and residue Arginine 253 with a bond length of 1.89 Å and 2.30 Å at the NF-κβ receptor. NE was optimized using Central Composite Rotatable Design (CCRD). The globule size of chitosan coated NE, Polydispersity index (PDI) and zeta potential were 183.7 ± 5.2 nm, 0.263 ± 0.005, and 24.9 mV respectively. NE exhibited 85.28% transmittance showing the formulation was clear and transparent. TEM showed that NE had spherical globules with no aggregation. The formulation had a stable pH value of 5.8 ± 0.18. In vitro release and permeation studies exhibited 2 folds and 3.4 folds enhancement when compared with the drug suspension. Neurobehavioral activity and biochemical parameters corroborated well with the pharmacokinetic results. Histopathological study and immunohistochemical analysis were performed to get better picture of 6-OHDA induced toxicity and reversal of PD symptoms. Thus, the NE tailored is a promising synergistic approach yielding enticing outcomes for better management of PD related symptoms. [ABSTRACT FROM AUTHOR]