Thirteen Hypericum species growing in Bulgaria were investigated for free radical-scavenging activity, antioxidant activity, total tannins and total flavonoids contents. Methanolic extracts from the Hypericum species were analyzed for radical scavenging and antioxidant activities using DPPH-, ABTS- free radicals, total antioxidant activity and inhibition of lipid peroxidation by ferric thiocyanate (FTC) method. Butylated hydroxytoluene and ascorbic acid were used as positive controls. Methanolic extracts from H. cerastoides, H. perforatum and H. maculatum demonstrate the highest antioxidant activities and are potential sources of natural antioxidant compounds. The quantification of tannins and flavanoids were determined in Hypericum species using Folin-Chiocalteu reagent and AlCl3, respectively. The amounts of the tannins ranged from 1.30 ± 0.01 mg/100 g dw in H. elegans to 8.67 ± 0.02 g/100 g dw in H. perforatum. The highest concentration of flavonoids was found in H. cerastoides (1.22 ± 0.02 g/100g dw), and the lowest amount was established in H. olympicum (0.20 ± 0.03 g/100g dw).

Oxidative stress is implicated in the pathogenesis of different human diseases: Alzheimer, Parkinson, Huntington, amyotrophic lateral sclerosis (Lou Gehrig's disease), Down’s syndrome, atherosclerosis, vascular disease, cancer, diabetes mellitus type 1 and type 2, age – related macular degeneration, psoriatic arthritis. The aim of current study is to summarize the scientific evidences for the antioxidant and neuroprotective activity of Galantamine and some of its derivatives. Galantamine is a scavenger of reactive oxygen species and causes neuroprotective effect by lowering the oxidative neuronal damage, through the following pathways: 1) prevention of the activation of P₂X₇ receptors; 2) protection of mitochondrial membrane potential; 3) pre – vention of the membrane fluidity disturbances. Another mechanism is the decreasing of the overproduction of reactive oxygen species, a result from the increasing of acetylcholine level due to: 1) acethylcholinesterase inhibition; 2) allosteric potentiation of α7 – subtype of nicotinic acetylcholine receptors. A close relationship between acethylcholinesterase inhibition and reduced oxidative injury is observed. Through allosteric potentiation of the α7 – subtype of nicotinic acetylcholine receptors, the drug leads to induction of phosphorylation of serine – threonine protein kinase, stimulates phosphoinositide 3 – kinase and elevates the expression of protective protein Bcl – 2. By activation of these important neuroprotective cascades, Galantamine exerts neuroprotection against a variety of cytotoxic agents (β – amyloid peptide, glutamate, hydrogen peroxide, oxygen and glucose deprivation). The new trend in therapy of Alzheimer's disease will be the investigation and application of compounds such as Galantamine derivatives, which possess acethylcholinesterase and γ – secretase inhibitory activity and antioxidant properties.

Background: Amorpha fruticosa L. and Phytolacca americana L. are native plants for North America, but invasive for Central Europe and the Mediterranean areas. Previous investigation reported DPPH radical scavenging activity of A. fruticosa seeds from Mississippi river basin and P. americana berries from Iran. The aim of the present study was to investigate methanol extracts from leaves and fruits of these invasive species growing in Bulgaria for radical scavenging and acetylcholinesterase inhibitory potential. Materials and Methods: Antioxidant activity was investigated using DPPH and ABTS free radicals; FRAP assay and inhibition of lipid peroxidation in linoleic acid system by FTC. Modified Ellman's colorimetric method was carried out to quantify acetylcholinesterase inhibition potential. In addition, the quantities of total polyphenols, flavonoids, and hydroxycinnamic derivatives were determinated using Folin-Chiocalteu reagent, AlCl ₃ , and Na ₂ MoO ₄ , respectively. Results: The highest concentrations of total polyphenols and flavonoids were found in A. fruticosa leaves (786.70±1.78 mg/g dry extract and 32.19±0.29 mg/g dry extract, respectively). A. fruticosa fruit was found to be the most enriched in total hydroxycinnamic derivatives (153.55±1.11 mg/g dry extract) and demonstrated the highest antioxidant activity: DPPH, IC ₅₀ 9.83 μg/mL; ABTS, IC ₅₀ 2.90 μg/mL; FRAP _, 642.95±3.95 μg TE/mg de, and acetylcholinesterase inhibitory activity, 48.86±0.55% (2 mg/mL). Conclusions: Phytolacca americana leaves and Amorpha fruticosa could be useful in therapy of free radical pathologies and neurodegenerative disorders.

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation.

Alzheimer’s disease (AD) is considered a complex neurodegenerative condition which warrants the development of multitargeted drugs to tackle the key pathogenetic mechanisms of the disease. In this study, two novel series of melatonin- and donepezil-based hybrid molecules with hydrazone (3a–r) or sulfonyl hydrazone (5a–l) fragments were designed, synthesized, and evaluated as multifunctional ligands against AD-related neurodegenerative mechanisms. Two lead compounds (3c and 3d) exhibited a well-balanced multifunctional profile, demonstrating intriguing acetylcholinesterase (AChE) inhibition, promising antioxidant activity assessed by DPPH, ABTS, and FRAP methods, as well as the inhibition of lipid peroxidation in the linoleic acid system. Compound 3n, possessing two indole scaffolds, showed the highest activity against butyrylcholinesterase (BChE) and a high selectivity index (SI = 47.34), as well as a pronounced protective effect in H₂O₂-induced oxidative stress in SH-SY5Y cells. Moreover, compounds 3c, 3d, and 3n showed low neurotoxicity against malignant neuroblastoma cell lines of human (SH-SY5Y) and murine (Neuro-2a) origin, as well as normal murine fibroblast cells (CCL-1) that indicate the in vitro biocompatibility of the experimental compounds. Furthermore, compounds 3c, 3d, and 3n were capable of penetrating the blood–brain barrier (BBB) in the experimental PAMPA-BBB study. The molecular docking showed that compound 3c could act as a ligand to both MT1 and MT2 receptors, as well as to AchE and BchE enzymes. Taken together, those results outline compounds 3c, 3d, and 3n as promising prototypes in the search of innovative compounds for the treatment of AD-associated neurodegeneration with oxidative stress. This study demonstrates that hydrazone derivatives with melatonin and donepezil are appropriate for further development of new AChE/BChE inhibitory agents.