Anti-Cholinergic Effects of the Phenolic Extract from the Astragalus crenatus Plant: A Computational and Network Pharmacology Study.

Investigations into cholinesterase inhibition have received attention from researchers in recent years for the treatment of Alzheimer's disease. Cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), hold pivotal significance in Alzheimer's disease (AD) treatment. In this study, we utilized the ethanolic extract of Astragalus crenatus followed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to separate and identify at least 21 compounds in the extract. Rosmarinic acid exhibited the highest concentration (96.675 ± 1.3 mg/g extract), succeeded by hesperidin (79.613 ± 1.2 mg/g extract), hesperetin (75.102 ± 1.4 mg/g extract), rutin (68.156 ± 1.6 mg/g extract), chlorogenic acid (67.645 ± 1.5 mg/g extract), fisetin (66.647 ± 2.3 mg/g extract), and hyperoside (63.173 ± 1.5 mg/g extract). A. crenatus extract efficiently inhibited both AChE and BChE activities in a dosage-dependent manner. Molecular docking was employed to scrutinize the anticholinesterase mechanisms of the identified phytocompounds. Notably, a network pharmacology analysis was executed for the most efficacious compound. Based on binding energies, hesperidin emerged as the most potent inhibitor against both AChE and BChE, exhibiting scores of -10.5 Kcal/mol and -9.8 Kcal/mol, respectively. Due to its dual inhibition of AChE and BChE activities, hesperidin from Astragalus crenatus holds promise for the development of novel therapeutics aimed at neurological disorders, particularly AD.

Chemical exploration of different extracts from Phytolacca americana leaves and their potential utilization for global health problems: in silico and network pharmacology validation.

Phytolacca americana L. is of great interest as a traditional additive in various folk remedies in several countries, including Turkey. We aimed to determine the chemical profile (assisted by high-Performance liquid chromatography-electrospray ionization-tandem mass apectrometry (HPLC-ESI-MS/MS) experiments of three extracts obtained by different polarity solvents viz. ethyl acetate (to extract semipolar compounds), methanol and water (to extract highly polar metabolites) from P. americana leaves. Their anti-diabetic effects were investigated in vitro by assessing their inhibition toα-amylase and α-glucosidase. Assessment of the neuroprotective potential of the three extracts was carried out against acetyl-(AChE) and butyryl-(BChE) cholinesterase enzymes. HPLC-ESI-MS/MS experiments showed a total of 17 chromatographic peaks primarily classified to six flavonoids, two saponins, and six fatty acids. Antioxidant assays revealed remarkable activity for the ethyl acetate and methanol extracts. The BChE inhibition was considerably more significant (4.08 mg galantamine equivalent (GALAE)/g) for the ethyl acetate extract, whereas the methanol extract had good inhibitory efficacy for AChE (2.05 mg GALAE/g). Through network pharmacology, the compounds' mechanism of action of targeted key gene in their associated diseases were identified. The hubb gene signal transducer and activator of transcription 3 (STAT3) and tumour necrosis factor (TNFα) where the P. americana compound's site of action in inflammation bowel disease. The results offer possibilities for the prospective application of P. americana in metabolic regulation, blood glucose control, and as a source of bioactive compounds with cholinesterase enzyme inhibitory characteristics which could be of relevance in the cosmetic or pharmaceutical industry for combating melanogenesis.Communicated by Ramaswamy H. Sarma.

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice.

This study aimed to investigate the chemical composition and antidiabetic properties of cultivated Hyoscyamus albus L. The ethanol extract was analyzed using LC-MS/MS, and 18 distinct phenolic compounds were identified. Among these, p-coumaric acid (6656.8 ± 3.4 µg/g), gallic acid (6516 ± 1.7 µg/g), luteolin (6251.9 ± 1.3 µg/g), apigenin (6209.9 ± 1.1 µg/g), and rutin (5213.9 ± 1.3 µg/g) were identified as the most abundant polyphenolic molecules. In the in vitro antidiabetic experiment, the ability of the plant extract to inhibit α-glucosidase and α-amylase activities was examined. The results indicated that the extract from H. albus L. exhibited a higher inhibitory effect on α-amylase compared to α-glucosidase, with an IC50 of 146.63 ± 1.1 µg/mL and 270.43 ± 1.1 µg/mL, respectively. Docking simulations revealed that luteolin, fisetin, and rutin exhibited the most promising inhibitory activity against both enzymes, as indicated by their high contrasting inhibition scores. To further investigate the in vivo antidiabetic effects of H. albus L., an experiment was conducted using STZ-induced diabetic mice. The results demonstrated that the plant extract effectively reduced the levels of cholesterol and triglycerides. These findings suggest that H. albus L. may have therapeutic potential for managing hyperlipidemia, a common complication associated with diabetes. This highlights its potential as a natural remedy for diabetes and related conditions.

Ultrasound-Assisted Extraction, LC-MS/MS Analysis, Anticholinesterase, and Antioxidant Activities of Valuable Natural Metabolites from Astragalus armatus Willd.: In Silico Molecular Docking and In Vitro Enzymatic Studies.

The Astragalus armatus Willd. plant's phenolic constituent extraction and identification were optimized using the ultrasound-assisted extraction (UAE) method and the LC-MS/MS analysis, respectively. Additionally, cupric reducing antioxidant capacity (CUPRAC), beta carotene, reducing power, DMSO alcalin, silver nanoparticle (SNP)-based method, phenanthroline, and hydroxyl radical tests were utilized to assess the extract's antioxidant capacity, while the neuroprotective effect was examined in vitro against acetylcholinesterase enzyme. This study accurately estimated the chemical bonding between the identified phenolic molecules derived from LC-MS/MS and the AChE. The extract was found to contain sixteen phenolic substances, and rosmarinic, protocatechuic, and chlorogenic acids, as well as 4-hydroxybenzoic, hyperoside, and hesperidin, were the most abundant substances in the extract. In all antioxidant experiments, the plant extract demonstrated strong antioxidant activity and a significant inhibitory impact against AChE (40.25 ± 1.41 µg/mL). According to molecular docking affinity to the enzyme AChE, the top-five molecules were found to be luteolin, quercetin, naringenin, rosmarinic acid, and kaempferol. Furthermore, these tested polyphenols satisfy the essential requirements for drug-like characteristics and Lipinski's rule of five. These results highlight the significance of the A. armatus plant in cosmetics, as food additives, and in the pharmaceutical industry due to its rosmarinic and chlorogenic acid content.

Investigation of Photoprotective, Anti-Inflammatory, Antioxidant Capacities and LC-ESI-MS Phenolic Profile of Astragalus gombiformis Pomel.

Plant-derived compounds have recently been gaining popularity as skincare factors due to their ability to absorb ultraviolet radiations and their anti-inflammatory, and antioxidant properties. In this light, this work aimed to evaluate in vitro the pharmacological activities of the butanolic extract prepared from the aerial parts of Astragalus gombiformis Pomel, an endemic species to southern Algeria. The sun protection factor was used to assess the photoprotective effect (SPF), the protein denaturation method to determine the anti-inflammatory activity, and brine shrimp nauplii and OxHLIA assay, respectively, to assess the cytotoxicity and antioxidant capacity of A. gombiformis. In addition, LC-ESI-MS analysis was employed for the characterization of the phenolic constituents of A. gombiformis. The results showed that A. gombiformis had high capacity for absorbing UV radiations with an SPF of 37.78 ± 0.85 and significant anti-inflammatory activity with a percentage inhibition of 75.38% which is close to that of diclofenac and ketoprofen. In addition, A. gombiformis was found to have effective cytotoxicity against Artemia nauplii with a DC50 value of about 44.7 µg/mL, but a weak hemolytic effect against human erythrocytes. LC-ESI-MS results detected the presence of 17 phenolic compounds with a predominance of cirsiliol, silymarin, quercitrin (quercetin-3-O-rhamnoside), and kaempferol. Taken together, these results suggest that A. gombiformis extract could be used as a skincare agent in cosmetic formulations, providing excellent antioxidant and anti-inflammatory protection, allowing the treatment of skin conditions, as well as a pharmaceutical agent with multidimensional applications.