Magnolol and luteolin are two natural compounds recognized in several medicinal plants widely used in traditional medicine, including type 2 diabetes mellitus. This research aimed to determine the inhibitory activity of magnolol and luteolin on α-glucosidase activity. Their biological profile was studied by multispectroscopic methods along with inhibitory kinetic analysis and computational experiments. Magnolol and luteolin decreased the enzymatic activity in a concentration-dependent manner. With 0.075 µM α-glucosidase, the IC₅₀ values were similar for both compounds (~ 32 µM) and significantly lower than for acarbose (815 μM). Magnolol showed a mixed-type antagonism, while luteolin showed a non-competitive inhibition mechanism. Thermodynamic parameters suggested that the binding of magnolol was predominantly sustained by hydrophobic interactions, while luteolin mainly exploited van der Waals contacts and hydrogen bonds. Synchronous fluorescence revealed that magnolol interacted with the target, influencing the microenvironment around tyrosine residues, and circular dichroism explained a rearrangement of the secondary structure of α-glucosidase from the initial α-helix to the final conformation enriched with β-sheet and random coil. Docking studies provided support for the experimental results. Altogether, the data propose magnolol, for the first time, as a potential α-glucosidase inhibitor and add further evidence to the inhibitory role of luteolin.

Diabetes mellitus is characterized by chronic hyperglycemia that promotes ROS formation, causing severe oxidative stress. Furthermore, prolonged hyperglycemia leads to glycation reactions with formation of AGEs that contribute to a chronic inflammatory state. This research aims to evaluate the inhibitory activity of α-mangostin and four synthetic xanthenone derivatives against glycation and oxidative processes and on α-glucosidase, an intestinal hydrolase that catalyzes the cleavage of oligosaccharides into glucose molecules, promoting the postprandial glycemic peak. Antiglycation activity was evaluated using the BSA assay, while antioxidant capacity was detected with the ORAC assay. The inhibition of α-glucosidase activity was studied with multispectroscopic methods along with inhibitory kinetic analysis. α-Mangostin and synthetic compounds at 25 µM reduced the production of AGEs, whereas the α-glucosidase activity was inhibited only by the natural compound. α-Mangostin decreased enzymatic activity in a concentration-dependent manner in the micromolar range by a reversible mixed-type antagonism. Circular dichroism revealed a rearrangement of the secondary structure of α-glucosidase with an increase in the contents of α-helix and random coils and a decrease in β-sheet and β-turn components. The data highlighted the anti-α-glucosidase activity of α-mangostin together with its protective effects on protein glycation and oxidation damage.

The aqueous decoctions of Vernonia amygdalina (VA) leaves and roots are widely used in traditional African medicine as an antidiabetic remedy. The amount of luteolin and vernodalol in leaf and root extracts was detected, and their role was studied regarding α-glucosidase activity, bovine serum albumin glycation (BSA), reactive oxygen species (ROS) formation, and cell viability, together with in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Vernodalol did not affect α-glucosidase activity, whereas luteolin did. Furthermore, luteolin inhibited the formation of advanced glycation end products (AGEs) in a concentration-dependent manner, whereas vernodalol did not reduce it. Additionally, luteolin exhibited high antiradical activity, while vernodalol demonstrated a lower scavenger effect, although similar to that of ascorbic acid. Both luteolin and vernodalol inhibited HT-29 cell viability, showing a half-maximum inhibitory concentration (IC₅₀) of 22.2 µM (−Log IC₅₀ = 4.65 ± 0.05) and 5.7 µM (−Log IC₅₀ = 5.24 ± 0.16), respectively. Finally, an in silico ADMET study showed that both compounds are suitable candidates as drugs, with appropriate pharmacokinetics. This research underlines for the first time the greater presence of vernodalol in VA roots compared to leaves, while luteolin is prevalent in the latter, suggesting that the former could be used as a natural source of vernodalol. Consequently, root extracts could be proposed for vernodalol-dependent antiproliferative activity, while leaf extracts could be suggested for luteolin-dependent effects, such as antioxidant and antidiabetic effects.

The discovery of new oral antidiabetic drugs remains a priority in medicine. This research aimed to evaluate the activity of the flavonoid baicalein and its natural glucuronide baicalin, compared to the antidiabetic drug metformin, as potential antiglycation, anti–radical, and anti-α–glucosidase agents, in order to assess their potential role in counteracting hyperglycemia-induced tissue damage. The study considered: (i) the BSA assay, to detect the formation of advanced glycation end products (AGEs), (ii) the GK peptide–ribose assay, which evaluates the cross–linking between the peptide and ribose, and (iii) the carbonyl content assay to detect the total carbonyl content, as a biomarker of tissue damage. In addition, to obtain a reliable picture of the antiglycation capacity of the investigated compounds, DPPH scavenging and oxygen radical absorbance capacity (ORAC) assays were performed. Furthermore, the anti–α–glucosidase activity of baicalein and baicalin was detected. Furthermore, to estimate cell permeability, preliminarily, the cytotoxicity of baicalein and baicalin was evaluated in HT–29 human colon adenocarcinoma cells using the MTT assay. Successively, the ability of the compounds to pass through the cytoplasmic membranes of HT–29 cells was detected as a permeability screen to predict in vivo absorption, showing that baicalein passes into cells even if it is quickly modified in various metabolites, being its main derivative baicalin. Otherwise, baicalin per se did not pass through cell membranes. Data show that baicalein is the most active compound in reducing glycation, α-glucosidase activity, and free radicals, while baicalin exhibited similar activities, but did not inhibit the enzyme α–glucosidase.

The study of medicinal plants and their active compounds is relevant to maintaining knowledge of traditional medicine and to the development of new drugs of natural origin with lower environmental impact. From the seeds of the Brazilian plant Pterodon emarginatus, six different preparations were obtained: essential oil (EO), ethanol extract (EthE) prepared using the traditional method, and four extracts using solvents at different polarities, such as n-hexane, chloroform, ethyl acetate, and methanol (HexE, ChlE, EtAE, and MetE). Chemical characterization was carried out with gas chromatography, allowing the identification of several terpenoids as characteristic components. The two sesquiterpenes β-caryophyllene and farnesol were identified in all preparations of Pterodon emarginatus, and their amounts were also evaluated. Furthermore, the total flavonoid and phenolic contents of the extracts were assessed. Successively, the antiradical activity with DPPH and ORAC assays and the influence on cell proliferation by the MTT test on the human colorectal adenocarcinoma (HT-29) cell line of the preparations and the two compounds were evaluated. Lastly, an in silico study of adsorption, distribution, metabolism, excretion, and toxicity (ADMET) showed that β-caryophyllene and farnesol could be suitable candidates for development as drugs. The set of data obtained highlights the potential medicinal use of Pterodon emarginatus seeds and supports further studies of both plant preparations and isolated compounds, β-caryophyllene and farnesol, for their potential use in disease with free radical involvement as age-related chronic disorders.

trans-Tiliroside and (+)-pinoresinol, a flavonoid and a lignan found in plants traditionally used for diabetes mellitus care, were investigated for antidiabetic properties through in vitro and in silico studies. Four assays were conducted: Bovine Serum Albumin (BSA) assay to assess inhibition of albumin glycation, α-glucosidase assay to evaluate decrease of carbohydrate digestion, Oxygen Radical Absorbance Capacity (ORAC) assay for antioxidant activity and cytotoxicity evaluation on HT-29 cells. trans-Tiliroside showed higher inhibition of protein glycation, with IC₅₀ values of 113.6, 71.03 and 95.73 µM against glucose, fructose and ribose-induced glycation, respectively. Moreover, trans-tiliroside demonstrated higher antioxidant capacity than (+)-pinoresinol. Both compounds showed slight α-glucosidase inhibitory activity and no cytotoxicity in HT-29 cells at 0.1-100 µM. An in silico pharmacokinetic study evaluated their bioavailability. Results suggest trans-tiliroside can act as an inhibitor of protein glycation, potentially reducing unwanted glycation reactions and preventing hyperglycaemia-related diseases.