Background and Objectives: Alzheimer’s disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods: Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski’s rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (−8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders.

Ceratonia siliqua L. is a medicinal plant that has long been used in traditional Moroccan medicine to treat many diseases. This study aimed to assess the impact of the stages of the immature phase of carob pulp (M1, M2, M3, M4, and M5) on phytochemical composition, antioxidant activity, and antidiabetic activity of Ceratonia siliqua L. The identification of the phenolic profile by HPLC-UV/MS-MS and the study of the antidiabetic effect by in silico, in vitro, and in vivo studies were carried out for extracts with high contents of phenolic compounds from immature wild carob pulp from the communes of Timoulit (TM), Bin Elouidane (AW), and Ouaouizerth (TG) in the province of Azilal in the Béni Mellal-Khénifra region. The results revealed a gradual increase in total sugar content over the pulp’s ripening period, reaching a value of 2134 ± 56.23 mg GE/100 g fresh weight (FW) for TG. The three locations showed peak values for total polyphenol content (TPC), total flavonoid content (TFC), and total condensed tannin (TCT) at the M2 stage. AW had the highest concentrations of TPC (3819 ± 226.4 mg GAE/100 g FM), TFC (1034 ± 57.08 mg QE/100 g FM), and TCT (1472 ± 28.46 mg CE/100 g FM). The DPPH assay (7892 ± 296.1 mg TE/100 g FM) and the FRAP assay (278.2 ± 7.85 mg TE/100 g FM) both demonstrated that the TG zone is a highly potent antioxidant zone. In contrast, the AW site exhibited a markedly elevated value of 725.4 ± 103.6 mg TE/100 g FM in the ABTS assay. HPLC-UV-MS/MS analysis showed that the methanolic extracts of immature carob pulp (MEICP) from the three areas contained several different chemical compounds. The most prevalent were 3-O-p-coumaroyl-5-O-caffeoylquinic acid, quercetin 3-methyl ether, gallic acid, and galloylquinic acid. Immature carob pulp extract (ICPE) from AW showed the strongest in vitro inhibition of pancreatic α-amylase (IC₅₀ = 0.405 µg/mL) and TG extracts were most potent against intestinal α-glucosidase (IC₅₀ = 0.063 µg/mL). In vivo, AW, TG, and TM extracts significantly reduced postprandial glycemia in rats, with AW having the greatest effect. These results highlight the antidiabetic potential of ICPE. The 3-O-p-Coumaroyl-5-O-caffeoylquinic acid showed better affinity for α-amylase compared to acarbose and interacted significantly with several amino acid residues of the enzyme. Similarly, this molecule and 3,4-Dicaffeoylquinic acid demonstrated a strong affinity for α-glucosidase, suggesting their potential as natural inhibitors of enzymes involved in carbohydrate metabolism. Most of the compounds are not substrates of P-glycoprotein and exhibited high intestinal absorption. Furthermore, the majority of these compounds did not act as inhibitors or substrates of CYP450 enzymes, reinforcing their suitability for development as oral medications. These results underscore the potential of immature carob pulp as a promising antidiabetic agent.

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a–5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a “click chemistry” approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including ¹H NMR, ¹³C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of −9.9 and −9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski’s criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development.

In this study, we aimed to compare the phytochemical compounds (polyphenols and flavonoids), antioxidant activity, functional groups present in the compounds (FTIR), and anti-microbial effects, in aqueous and methanol extracts obtained from flowers of commercial Hypericum perforatum and native...

Introduction: Laurus nobilis L., a botanical name for bay leaf, is a widely used spice and medicinal herb. The purpose of this research is to examine the effects of solvent extraction, plant stage, and sex on the phytochemical composition and antioxidant activity of crude extracts obtained from the roots, shoots, and leaves of male and female L. nobilis shrubs that are cultivated in Northern Morocco. Method: Primary and secondary metabolites were found by phytochemical screening, and colorimetric techniques were used to measure the total phenolic, flavonoid, and flavanol concentrations. Gas Chromatography-Mass Spectroscopy (GC-FID) was used to examine the extract's phytoconstituents. Antioxidant activity was assessed using phosphomolybdate, DPPH, and ABTS tests. Results: According to the findings, L. nobilis is a rich source of bioactive chemicals that may be used in therapeutic and medical settings. extracts of female tree shoots and leaves had the greatest total phenolic contents. The leaves of both male and female trees had the greatest total flavonoid content. Ten phenolic chemicals, including gallic acid, quercetin, and caffeic acid, were found in variable amounts in all of the extracts according to the GC-FID analysis. According to the ABTS technique, female tree shoots and shrub leaves had the greatest levels of antioxidant activity. Furthermore, the ADME study revealed that most compounds had high intestinal absorption, fulfilling the Lipinski criterion and indicating their potential for development as oral drugs. Discussion: The phytochemical characteristics and antioxidant activities of L. nobilis L. may be significantly impacted by sex, plant stage, and solvent extraction, as shown by these studies, which also highlight the plant's potential for use in the pharmaceutical, food, and cosmetics sectors.

Azadirachta indica , commonly known as neem or Mim in Chad, is recognized for its significant biological activities and is used for medicinal purposes. This study quantifies phenolic content, analyzes chemical composition via high-performance liquid chromatography–mass spectrometry, and evaluates the antioxidant activity of Mim leaf extracts with ethanol (ELE) and water (WLE). The analysis identified bioactive compounds with strong radical scavenging activity and conducted in silico studies by molecular docking with AutoDock Tools. Crystal structures were sourced from the Protein Data Bank, and the Swiss absorption, distribution, metabolism, and excretion platform analyzed the pharmacokinetic properties. Results indicated that WLE had a higher phenolic content (264.7 ± 0.03 µg gallic acid equivalent [GAE]/mg) compared to ELE (135.3 ± 0.05 µg GAE/mg). Flavonoid content was greater in ELE (138.33 ± 0.002 µg catechin equivalent [CE]/mg) than in WLE (83.38 ± 0.002 µg CE/mg). Major compounds identified through high-performance liquid chromatography coupled to mass spectrometry included diethyl phthalate in ELE (92.31%) and butylated hydroxytoluene (BHT) in WLE (28.12%). Antioxidant activities measured by 2,2-di-phenyl-1-picrylhydrazyl, 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid), and ferric-reducing power assays showed promising results for both extracts. BHT demonstrated a better affinity for glutathione reductase and lipoxygenases, while vanillin showed a strong affinity for cyclooxygenase. Most compounds exhibited high intestinal absorption and are not P-glycoprotein substrates, indicating potential for oral medication. Finally, Mim extracts contain diverse compounds that contribute to their notable antioxidant activity.