Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches.

Series of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23±2.91 µM, while the reference (galantamine) had IC50 =1.85±0.12 µM. Compounds 9 (IC50 75.14±1.82 µM), 13 (IC50 =16.14±0.43 µM), were determined to be stronger BChE inhibitors than the reference galantamine (IC50 =93.53±2.23 µM). The IC50 value of compound 16 for BChE inhibition (IC50 =126.56±11.96 µM) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.

Bay Leaf (Laurus Nobilis L.) Incense Improved Scopolamine-Induced Amnesic Rats by Restoring Cholinergic Dysfunction and Brain Antioxidant Status.

Bay leaf (Laurus nobilis L.) has been shown to possesses various biological activities such as wound healing activity, antioxidant activity, antibacterial activity, antiviral activity, immunostimulant activity, anticholinergic activity, antifungal activity, insect repellant activity, anticonvulsant activity, antimutagenic activity, and analgesic and anti-inflammatory activity. The present study aimed to investigate whether the bay leaf incense (BL) elicits the memory formation via the action on the cholinergic system using a scopolamine (Sco)-induced rat model. Rats were exposed to BL over 5 min in a smoking chamber apparatus once daily for 22 days, whereas memory impairment was induced by Sco (0.7 mg/kg), a muscarinic receptor antagonist, delivered 30 min before each behavioral test. The phytochemical composition of BL was achieved by gas chromatograph-mass spectrometry (GCMS). Behavioral effects in rats were assessed by Y-maze, radial arm maze (RAM), and novel object recognition (NOR) paradigms. Additionally, the acetylcholinesterase (AChE) activity and the oxidative stress markers in the rat hippocampus were also evaluated. Exposure to BL significantly ameliorated Sco-induced cognitive impairment and oxidative stress in the rat hippocampus. The obtained results suggested that BL-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic system and antioxidant activities.

Cognitive Facilitation and Antioxidant Effects of an Essential Oil Mix on Scopolamine-Induced Amnesia in Rats: Molecular Modeling of In Vitro and In Vivo Approaches.

The present study investigated the capability of an essential oil mix (MO: 1% and 3%) in ameliorating amnesia and brain oxidative stress in a rat model of scopolamine (Sco) and tried to explore the underlying mechanism. The MO was administered by inhalation to rats once daily for 21 days, while Sco (0.7 mg/kg) treatment was delivered 30 min before behavioral tests. Donepezil (DP: 5 mg/kg) was used as a positive reference drug. The cognitive-enhancing effects of the MO in the Sco rat model were assessed in the Y-maze, radial arm maze (RAM), and novel object recognition (NOR) tests. As identified by gas chromatography-mass spectrometry (GC-MS), the chemical composition of the MO is comprised by limonene (91.11%), followed by γ-terpinene (2.02%), ß-myrcene (1.92%), ß-pinene (1.76%), α-pinene (1.01%), sabinene (0.67%), linalool (0.55%), cymene (0.53%), and valencene (0.43%). Molecular interactions of limonene as the major compound in MO with the active site of butyrylcholinesterase (BChE) was explored via molecular docking experiments, and Van der Waals (vdW) contacts were observed between limonene and the active site residues SER198, HIS438, LEU286, VAL288, and PHE329. The brain oxidative status and acetylcholinesterase (AChE) and BChE inhibitory activities were also determined. MO reversed Sco-induced memory deficits and brain oxidative stress, along with cholinesterase inhibitory effects, which is an important mechanism in the anti-amnesia effect. Our present findings suggest that MO ameliorated memory impairment induced by Sco via restoration of the cholinergic system activity and brain antioxidant status.

Therapeutic Potential of α- and ß-Pinene: A Miracle Gift of Nature.

α- and ß-pinene are well-known representatives of the monoterpenes group, and are found in many plants' essential oils. A wide range of pharmacological activities have been reported, including antibiotic resistance modulation, anticoagulant, antitumor, antimicrobial, antimalarial, antioxidant, anti-inflammatory, anti-Leishmania, and analgesic effects. This article aims to summarize the most prominent effects of α- and ß-pinene, namely their cytogenetic, gastroprotective, anxiolytic, cytoprotective, anticonvulsant, and neuroprotective effects, as well as their effects against H2O2-stimulated oxidative stress, pancreatitis, stress-stimulated hyperthermia, and pulpal pain. Finally, we will also discuss the bioavailability, administration, as well as their biological activity and clinical applications.

The effects of baicalein and baicalin on mitochondrial function and dynamics: A review.

Mitochondria play an essential role in cell survival by providing energy, calcium buffering, and regulating apoptosis. A growing body of evidence shows that mitochondrial dysfunction and its consequences, including impairment of the mitochondrial respiratory chain, excessive generation of reactive oxygen species, and excitotoxicity, play a pivotal role in the pathogenesis of different diseases such as neurodegenerative diseases, neuropsychiatric disorders, and cancer. The therapeutical role of flavonoids on these diseases is gaining increasing acceptance. Numerous studies on experimental models have revealed the favorable role of flavonoids on mitochondrial function and structure. This review highlights the promising role of baicalin and its aglycone form, baicalein, on mitochondrial function and structure with a focus on its therapeutic effects. We also discuss their chemistry, sources and bioavailability.

Anti-acetylcholinesterase and antioxidant assets of the major components (salicin, amentoflavone, and chlorogenic acid) and the extracts of Viburnum opulus and Viburnum lantana and their total phenol and flavonoid contents.

Some Viburnum species are used for preparation of the traditional drink called gilaburu in Anatolia. In the current study, our goal was to evaluate acetylcholinesterase (AChE) inhibitory and antioxidant activities of the ethyl acetate, methanol, and water extracts prepared from the branches, leaves, and fruits of Viburnum opulus and Viburnum lantana along with salicin, amentoflavone, and chlorogenic acid, three major compounds abundantly found in these species. AChE enzyme inhibition was tested in vitro using an enzyme-linked immunosorbent assay microplate reader at 50, 100, and 200 µL/mL concentrations. Antioxidant activity was examined by ferrous ion chelating capacity, ferric reducing antioxidant power, and ß-carotene bleaching assay at 500, 1,000, and 2,000 µg/mL. Total phenol and flavonoid contents of the extracts were also established by Folin-Ciocalteau and AlCl(3) reagents, respectively. Our data revealed that the leaf methanol extract of V. opulus displayed a significantly high inhibitory effect against AChE (57.63 ± 1.23%, 87.41 ± 0.99%, and 93.19 ± 0.87% at 50, 100, and 200 µg/mL, respectively). The extracts of V. lantana exerted higher antioxidant activity.

Radical quenching activity, ferric-reducing antioxidant power, and ferrous ion-chelating capacity of 16 Ballota species and their total phenol and flavonoid contents.

The ethyl acetate, methanol, and water extracts of 16 Ballota species (Family Lamiaceae)-Ballota acetabulosa, Ballota antalyanse, Ballota cristata, Ballota glandulosissima, Ballota inaequidens, Ballota larendana, Ballota latibracteolata, Ballota macrodonta, Ballota nigra ssp. anatolica, B. nigra ssp. foetida, B. nigra ssp. nigra, B. nigra ssp. uncinata, Ballota pseudodictamnus ssp. lycia, Ballota rotundifolia, Ballota saxatilis ssp. brachyodonta, and B. saxatilis subsp. saxatilis-were screened for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical quenching, ferric-reducing antioxidant power, and ferrous ion-chelating capacity at 1mg/mL. Hispanolone, a major diterpene found in the Ballota genus, was also tested in the same manner. Total phenol and flavonoid contents of the extracts were determined by Folin-Ciocalteau and AlCl(3) reagents, respectively. The extracts showed insignificant quenching activity against DPPH radical, but they had moderate antioxidant activity (0.597 ± 0.03 to 1.342 ± 0.01) in the ferric-reducing test compared to chlorogenic acid (the reference compound) (3.618 ± 0.01). All of the extracts (ranging from 65.1 ± 0.64% to 96.3 ± 0.09%) and hispanolone (97.31 ± 0.30%) exerted a remarkable ferrous ion-chelating effect. The highest total phenol (gallic acid equivalent) and flavonoid (quercetin equivalent) contents were found in the ethyl acetate extract of B. glandulosissima (393.7 ± 3.03 and 140.6 ± 1.97 mg/g of extract, respectively). Therefore, Ballota species could be a good source of natural preservatives in foodstuffs.

Polyprenyl-hydroquinones and -furans from three marine sponges inhibit the cell cycle regulating phosphatase CDC25A.

The CDC25 phosphatases regulate the cell division cycle by controlling the activity of cyclin-dependent kinases. While screening for inhibitors of phosphatases among natural products we repeatedly found that some polyprenyl-hydroquinones and polyprenyl-furans (furanoterpenoids) (furospongins, furospinosulins) were potent CDC25 phosphatase inhibitors. These compounds were extracted, isolated and identified independently from three sponge species (Spongia officinalis, Ircinia spinulosa, Ircinia muscarum), collected at different locations in the Mediterranean Sea. The compounds were inactive on the Ser/Thr phosphatase PP2C-alpha and on three kinases (CDK1, CDK5, GSK-3), suggesting that some potent and selective CDC25 phosphatase might be designed from these initial structures.