Inhibitory Effect of Fisetin on α-Glucosidase Activity: Kinetic and Molecular Docking Studies

The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be effective in alleviating hyperglycemia by inhibiting α-glucosidase. In this study, the α-glucosidase inhibitory activity of fisetin extracted from Cotinus coggygria Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC₅₀ value of 4.099 × 10⁻⁴ mM. Enzyme kinetic analysis revealed that fisetin is a non-competitive inhibitor of α-glucosidase, with an inhibition constant value of 0.01065 ± 0.003255 mM. Moreover, fluorescence spectrometric measurements indicated the presence of only one binding site between fisetin and α-glucosidase, with a binding constant (lgKa) of 5.896 L·mol⁻¹. Further molecular docking studies were performed to evaluate the interaction of fisetin with several residues close to the inactive site of α-glucosidase. These studies showed that the structure of the complex was maintained by Pi-Sigma and Pi-Pi stacked interactions. These findings illustrate that fisetin extracted from Cotinus coggygria Scop. is a promising therapeutic agent for the treatment of T2DM.     

Two Key Amino Acids Variant of α-l-arabinofuranosidase from Bacillus subtilis Str. 168 with Altered Activity for Selective Conversion Ginsenoside Rc to Rd

α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, the ginsenoside Rc-hydrolyzing α-l-arabinofuranosidase gene, BsAbfA, was cloned from Bacilus subtilis, and its codons were optimized for efficient expression in E. coli BL21 (DE3). The recombinant protein BsAbfA fused with an N-terminal His-tag was overexpressed and purified, and then subjected to enzymatic characterization. Site-directed mutagenesis of BsAbfA was performed to verify the catalytic site, and the molecular mechanism of BsAbfA catalyzing ginsenoside Rc was analyzed by molecular docking, using the homology model of sequence alignment with other β-glycosidases. The results show that the purified BsAbfA had a specific activity of 32.6 U/mg. Under optimal conditions (pH 5, 40 °C), the kinetic parameters K_m of BsAbfA for pNP-α-Araf and ginsenoside Rc were 0.6 mM and 0.4 mM, while the K_cat/K_m were 181.5 s⁻¹ mM⁻¹ and 197.8 s⁻¹ mM⁻¹, respectively. More than 90% of ginsenoside Rc could be transformed by 12 U/mL purified BsAbfA at 40 °C and pH 5 in 24 h. The results of molecular docking and site-directed mutagenesis suggested that the E173 and E292 variants for BsAbfA are important in recognizing ginsenoside Rc effectively, and to make it enter the active pocket to hydrolyze the outer arabinofuranosyl moieties at C₂₀ position. These remarkable properties and the catalytic mechanism of BsAbfA provide a good alternative for the effective biotransformation of the major ginsenoside Rc into Rd.     

Cloning,Expression, Purification,and Characterization of β-Galactosidase from Bifidobacterium longum and Bifidobacterium pseudocatenulatum

Expression and purification of β-galactosidases derived from Bifidobacterium provide a new resource for efficient lactose hydrolysis and lactose intolerance alleviation. Here, we cloned and expressed two β-galactosidases derived from Bifidobacterium. The optimal pH for BLGLB1 was 5.5, and the optimal temperature was 45 °C, at which the enzyme activity of BLGLB1 was higher than that of commercial enzyme E (300 ± 3.6 U/mg) under its optimal conditions, reaching 2200 ± 15 U/mg. The optimal pH and temperature for BPGLB1 were 6.0 and 45 °C, respectively, and the enzyme activity (0.58 ± 0.03 U/mg) under optimum conditions was significantly lower than that of BLGLB1. The structures of the two β-galactosidase were similar, with all known key sites conserved. When o-nitrophenyl-β-D-galactoside (oNPG) was used as an enzyme reaction substrate, the maximum reaction velocity (V_max) for BLGLB1 and BPGLB1 was 3700 ± 100 U/mg and 1.1 ± 0.1 U/mg, respectively. The kinetic constant (K_m) of BLGLB1 and BPGLB1 was 1.9 ± 0.1 and 1.3 ± 0.3 mmol/L, respectively. The respective catalytic constant (k_cat) of BLGLB1 and BPGLB1 was 1700 ± 40 s⁻¹ and 0.5 ± 0.02 s⁻¹, respectively; the respective k_cat/K_m value of BLGLB1 and BPGLB1 was 870 L/(mmol∙s) and 0.36 L/(mmol∙s), respectively. The K_m, k_cat and V_max values of BLGLB1 were superior to those of earlier reported β-galactosidase derived from Bifidobacterium. Overall, BLGLB1 has potential application in the food industry.     

Chemical Characterization of Plant Extracts and Evaluation of their Nematicidal and Phytotoxic Potential

Nacobbus aberrans ranks among the “top ten” plant-parasitic nematodes of phytosanitary importance. It causes significant losses in commercial interest crops in America and is a potential risk in the European Union. The nematicidal and phytotoxic activities of seven plant extracts against N. aberrans and Solanum lycopersicum were evaluated in vitro, respectively. The chemical nature of three nematicidal extracts (EC_50,48h ≤ 113 µg mL⁻¹) was studied through NMR analysis. Plant extracts showed nematicidal activity on second-stage juveniles (J2): (≥87%) at 1000 µg mL⁻¹ after 72 h, and their EC₅₀ values were 71.4–468.1 and 31.5–299.8 µg mL⁻¹ after 24 and 48 h, respectively. Extracts with the best nematicidal potential (EC_50,48h < 113 µg mL⁻¹) were those from Adenophyllum aurantium, Alloispermum integrifolium, and Tournefortia densiflora, which inhibited L. esculentum seed growth by 100% at 20 µg mL⁻¹. Stigmasterol (1), β-sitosterol (2), and α-terthienyl (3) were identified from A. aurantium, while 1, 2, lutein (4), centaurin (5), patuletin-7-β-O-glucoside (6), pendulin (7), and penduletin (8) were identified from A. integrifolium. From T. densiflora extract, allantoin (9), 9-O-angeloyl-retronecine (10), and its N-oxide (11) were identified. The present research is the first to report the effect of T. densiflora, A. integrifolium, and A. aurantium against N. aberrans and chemically characterized nematicidal extracts that may provide alternative sources of botanical nematicides.     

Phenolic compounds,essential oil composition,and antioxidant activity of Angelica purpurascens (Avé-Lall.) Gill

In this study, methanol extracts (MEs) and essential oil (EO) of Angelica purpurascens (Avé-Lall.) Gill obtained from different parts (root, stem, leaf, and seed) were evaluated in terms of antioxidant activity, total phenolics, compositions of phenolic compound, and essential oil with the methods of 2,2-azino-bis(3ethylbenzo-thiazoline-6-sulfonic acid (ABTS•⁺), 2,2-diphenyl-1-picrylhydrazil (DPPH•) radical scavenging activities, and ferric reducing/antioxidant power (FRAP), the Folin–Ciocalteu, liquid chromatography−tandem mass spectrometry (LC−MS/MS), and gas chromatography-mass spectrometry (GC−MS), respectively. The root extract of A. purpurascens exhibited the highest ABTS•⁺, DPPH•, and FRAP activities (IC₅₀: 0.05 ± 0.0001 mg/mL, IC₅₀: 0.06 ± 0.002 mg/mL, 821.04 ± 15.96 µM TEAC (Trolox equivalent antioxidant capacity), respectively). Moreover, EO of A. purpurascens root displayed DPPH• scavenging activity (IC₅₀: 2.95 ± 0.084 mg/mL). The root extract had the highest total phenolic content (438.75 ± 16.39 GAE (gallic acid equivalent), µg/mL)). Twenty compounds were identified by LC−MS/MS. The most abundant phenolics were ferulic acid (244.39 ± 15.64 μg/g extract), benzoic acid (138.18 ± 8.84 μg/g extract), oleuropein (78.04 ± 4.99 μg/g extract), and rutin (31.21 ± 2.00 μg/g extract) in seed, stem, root, and leaf extracts, respectively. According to the GC−MS analysis, the major components were determined as α-bisabolol (22.93%), cubebol (14.39%), α-pinene (11.63%), and α-limonene (9.41%) among 29 compounds. Consequently, the MEs and EO of A. purpurascens can be used as a natural antioxidant source.     

Optimising the Polyphenolic Content and Antioxidant Activity of Green Rooibos (Aspalathus linearis) Using Beta-Cyclodextrin Assisted Extraction

Antioxidant activity associated with green rooibos infusions is attributed to the activity of polyphenols, particularly aspalathin and nothofagin. This study aimed to optimise β-cyclodextrin (β-CD)-assisted extraction of crude green rooibos (CGRE) via total polyphenolic content (TPC) and antioxidant activity assays. Response surface methodology (RSM) permitted optimisation of β-CD concentration (0–15 mM), temperature (40–90 °C) and time (15–60 min). Optimal extraction conditions were: 15 mM β-CD: 40 °C: 60 min with a desirability of 0.985 yielding TPC of 398.25 mg GAE·g⁻¹, metal chelation (MTC) of 93%, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging of 1689.7 µmol TE·g⁻¹, ferric reducing antioxidant power (FRAP) of 2097.53 µmol AAE·g⁻¹ and oxygen radical absorbance capacity (ORAC) of 11,162.82 TE·g⁻¹. Aspalathin, hyperoside and orientin were the major flavonoids, with quercetin, luteolin and chrysoeriol detected in trace quantities. Differences (p < 0.05) between aqueous and β-CD assisted CGRE was only observed for aspalathin reporting the highest content of 172.25 mg·g⁻¹ of dry matter for extracts produced at optimal extraction conditions. Positive, strong correlations between TPC and antioxidant assays were observed and exhibited regression coefficient (R²) between 0.929–0.978 at p < 0.001. These results demonstrated the capacity of β-CD in increasing polyphenol content of green rooibos.     

GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies

Syzygium cumini (Pomposia) is a well-known aromatic plant belonging to the family Myrtaceae, and has been reported for its various traditional and pharmacological potentials, such as its antioxidant, antimicrobial, anti-inflammatory, and antidiarrheal properties. The chemical composition of the leaf essential oil via gas chromatography–mass spectrometry (GC/MS) analysis revealed the identification of fifty-three compounds representing about 91.22% of the total oil. The identified oil was predominated by α-pinene (21.09%), followed by β-(E)-ocimene (11.80%), D-limonene (8.08%), β-pinene (7.33%), and α-terpineol (5.38%). The tested oil revealed a moderate cytotoxic effect against human liver cancer cells (HepG2) with an IC₅₀ value of 38.15 ± 2.09 µg/mL. In addition, it effectively inhibited acetylcholinesterase with an IC₅₀ value of 32.9 ± 2.1 µg/mL. Furthermore, it showed inhibitory properties against α-amylase and α-glucosidase with IC₅₀ values of 57.80 ± 3.30 and 274.03 ± 12.37 µg/mL, respectively. The molecular docking studies revealed that (E)-β-caryophyllene, one of the major compounds, achieved the best docking scores of −6.75, −5.61, and −7.75 for acetylcholinesterase, α-amylase, and α-glucosidase, respectively. Thus, it is concluded that S. cumini oil should be considered as a food supplement for the elderly to enhance memory performance and for diabetic patients to control blood glucose.     

Construction of Magnetic Composite Bacterial Carrier and Application in 17β-Estradiol Degradation

Estrogen contamination is widespread and microbial degradation is a promising removal method; however, unfavorable environments can hinder microbial function. In this study, a natural estrogen 17β-estradiol (E2) was introduced as a degradation target, and a new combination of bacterial carrier was investigated. We found the best combination of polyvinyl alcohol (PVA) and sodium alginate (SA) was 4% total concentration, PVA:SA = 5:5, with nano-Fe₃O₄ at 2%, and maltose and glycine added to promote degradation, for which the optimal concentrations were 5 g·L⁻¹ and 10 g·L⁻¹, respectively. Based on the above exploration, the bacterial carrier was made, and the degradation efficiency of the immobilized bacteria reached 92.3% in 5 days. The immobilized bacteria were reused for three cycles, and the degradation efficiency of each round could exceed 94%. Immobilization showed advantages at pH 5, pH 11, 10 °C, 40 °C, and 40 g·L⁻¹ NaCl, and the degradation efficiency of the immobilized bacteria was higher than 90%. In the wastewater, the immobilized bacteria could degrade E2 to about 1 mg·L⁻¹ on the 5th day. This study constructed a bacterial immobilization carrier using a new combination, explored the application potential of the carrier, and provided a new choice of bacterial immobilization carrier.     

Chemical Variability and In Vitro Anti-Inflammatory Activity of Leaf Essential Oil from Ivorian Isolona dewevrei (De Wild. & T. Durand) Engl. & Diels

The chemical variability and the in vitro anti-inflammatory activity of the leaf essential oil from Ivorian Isolona dewevrei were investigated for the first time. Forty-seven oil samples were analyzed using a combination of CC, GC(RI), GC-MS and ¹³C-NMR, thus leading to the identification of 113 constituents (90.8–98.9%). As the main components varied drastically from sample to sample, the 47 oil compositions were submitted to hierarchical cluster and principal components analyses. Three distinct groups, each divided into two subgroups, were evidenced. Subgroup I−A was dominated by (Z)-β-ocimene, β-eudesmol, germacrene D and (E)-β-ocimene, while (10βH)-1β,8β-oxido-cadina-4-ene, santalenone, trans-α-bergamotene and trans-β-bergamotene were the main compounds of Subgroup I−B. The prevalent constituents of Subgroup II−A were germacrene B, (E)-β-caryophyllene, (5αH,10βMe)-6,12-oxido-elema-1,3,6,11(12)-tetraene and γ-elemene. Subgroup II−B displayed germacrene B, germacrene D and (Z)-β-ocimene as the majority compounds. Germacrene D was the most abundant constituent of Group III, followed in Subgroup III−A by (E)-β-caryophyllene, (10βH)-1β,8β-oxido-cadina-4-ene, germacrene D-8-one, and then in Subgroup III−B by (Z)-β-ocimene and (E)-β-ocimene. The observed qualitative and quantitative chemical variability was probably due to combined factors, mostly phenology and season, then harvest site to a lesser extent. The lipoxygenase inhibition by a leaf oil sample was also evaluated. The oil IC₅₀ (0.020 ± 0.005 mg/mL) was slightly higher than the non-competitive lipoxygenase inhibitor NDGA IC₅₀ (0.013 ± 0.003 mg/mL), suggesting a significant in vitro anti-inflammatory potential.     

Light Intensity and Photoperiod Affect Growth and Nutritional Quality of Brassica Microgreens

We explored the effects of different light intensities and photoperiods on the growth, nutritional quality and antioxidant properties of two Brassicaceae microgreens (cabbage Brassica oleracea L. and Chinese kale Brassica alboglabra Bailey). There were two experiments: (1) four photosynthetic photon flux densities (PPFD) of 30, 50, 70 or 90 μmoL·m⁻²·s⁻¹ with red:blue:green = 1:1:1 light-emitting diodes (LEDs); (2) five photoperiods of 12, 14, 16, 18 or 20 h·d⁻¹. With the increase of light intensity, the hypocotyl length of cabbage and Chinese kale microgreens shortened. PPFD of 90 μmol·m⁻²·s⁻¹ was beneficial to improve the nutritional quality of cabbage microgreens, which had higher contents of chlorophyll, carotenoids, soluble sugar, soluble protein and vitamin C, as well as increased antioxidant capacity. The optimal PPFD for Chinese kale microgreens was 70 μmol·m⁻²·s⁻¹. Increasing light intensity could increase the antioxidant capacity of cabbage and Chinese kale microgreens, while not significantly affecting glucosinolate (GS) content. The dry and fresh weight of cabbage and Chinese kale microgreens were maximized with a 14-h·d⁻¹ photoperiod. The chlorophyll, carotenoid and soluble protein content in cabbage and Chinese kale microgreens were highest for a 16-h·d⁻¹ photoperiod. The lowest total GS content was found in cabbage microgreens under a 12-h·d⁻¹ photoperiod and in Chinese kale microgreens under 16-h·d⁻¹ photoperiod. In conclusion, the photoperiod of 14~16 h·d⁻¹, and 90 μmol·m⁻²·s⁻¹ and 70 μmol·m⁻²·s⁻¹ PPFD for cabbage and Chinese kale microgreens, respectively, were optimal for cultivation.     

Formation of Lutein, β-Carotene and Astaxanthin in a Coelastrella sp. Isolate

In this study, the effect of media composition, N/P ratio and cultivation strategy on the formation of carotenoids in a Coelastrella sp. isolate was investigated. A two-stage process utilizing different media in the vegetative stage, with subsequent re-suspension in medium without nitrate, was employed to enhance the formation of carotenoids. The optimal growth and carotenoid content (β-carotene and lutein) in the vegetative phase were obtained by cultivation in M-8 and BG11 media. Use of a N/P ratio of 37.5 and low light intensity of 40 μmol m⁻² s⁻¹ (control conditions) led to optimal biomass production of up to 1.31 g L⁻¹. Low concentrations of astaxanthin (maximum of 0.31 wt. %) were accumulated under stress conditions (nitrogen-deficient medium containing 1.5 % of NaCl and light intensity of 500 μmol m⁻² s⁻¹), while β-carotene and lutein (combined maximum of 2.12 wt. %) were produced under non-stress conditions. Lipid analysis revealed that palmitic (C16:0) and oleic (C18:1) constituted the main algal fatty acid chains (50.2 ± 2.1% of the total fatty acids), while esterifiable lipids constituted 17.2 ± 0.5% of the biomass by weight. These results suggest that Coelastrella sp. could also be a promising feedstock for biodiesel production.     

In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

Diabetes mellitus (DM) is a chronic metabolic condition that can lead to significant complications and a high fatality rate worldwide. Efforts are ramping up to find and develop novel α-glucosidase and α-amylase inhibitors that are both effective and potentially safe. Traditional methodologies are being replaced with new techniques that are less complicated and less time demanding; yet, both the experimental and computational strategies are viable and complementary in drug discovery and development. As a result, this study was conducted to investigate the in vitro anti-diabetic potential of aqueous acetone Helichrysum petiolare and B.L Burtt extract (AAHPE) using a 2-NBDG, 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-d-glucose uptake assay. In addition, we performed molecular docking of the flavonoid constituents identified and quantified by liquid chromatography-mass spectrometry (LC-MS) from AAHPE with the potential to serve as effective and safe α-amylase and α-glucosidase inhibitors, which are important in drug discovery and development. The results showed that AAHPE is a potential inhibitor of both α-amylase and α-glucosidase, with IC₅₀ values of 46.50 ± 6.17 (µg/mL) and 37.81 ± 5.15 (µg/mL), respectively. This is demonstrated by a significant increase in the glucose uptake activity percentage in a concentration-dependent manner compared to the control, with the highest AAHPE concentration of 75 µg/mL of glucose uptake activity being higher than metformin, a standard anti-diabetic drug, in the insulin-resistant HepG2 cell line. The molecular docking results displayed that the constituents strongly bind α-amylase and α-glucosidase while achieving better binding affinities that ranged from ΔG = −7.2 to −9.6 kcal/mol (compared with acarbose ΔG = −6.1 kcal/mol) for α-amylase, and ΔG = −7.3 to −9.0 kcal/mol (compared with acarbose ΔG = −6.3 kcal/mol) for α-glucosidase. This study revealed the potential use of the H. petiolare plant extract and its phytochemicals, which could be explored to develop potent and safe α-amylase and α-glucosidase inhibitors to treat postprandial glycemic levels in diabetic patients.     

The Effects of Chemical Bonding at Subatomic Resolution: A Case Study on α-Boron

Similar to classical asphericity shifts, aspherical deformations of the electron density in the atomic core region can result in core asphericity shifts in refinements using a Hansen-Coppens multipolar model (HCM), especially when highly precise experimental datasets with resolutions far beyond sin(θ)/λ ≤ 1.0 Å⁻¹ are employed. These shifts are about two orders of magnitude smaller than their counterparts caused by valence shell deformations, and their underlying deformations are mainly of dipolar character for 1st row atoms. Here, we analyze the resolution dependence of core asphericity shifts in α-boron. Based on theoretical structure factors, an appropriate Extended HCM (EHCM) is developed, which is tested against experimental high-resolution (sin(θ)/λ ≤ 1.6 Å⁻¹) single-crystal diffraction data. Bond length deviations due to core asphericity shifts of α-boron in the order of 4–6·10⁻⁴ Å are small but significant at this resolution and can be effectively compensated by an EHCM, although the correlation of the additional model parameters with positional parameters prevented a free refinement of all core model parameters. For high quality, high resolution data, a proper treatment with an EHCM or other equivalent methods is therefore highly recommended.     

Inhibitory Activity and Mechanism Investigation of Hypericin as a Novel α-Glucosidase Inhibitor

α-glucosidase is a major enzyme that is involved in starch digestion and type 2 diabetes mellitus. In this study, the inhibition of hypericin by α-glucosidase and its mechanism were firstly investigated using enzyme kinetics analysis, real-time interaction analysis between hypericin and α-glucosidase by surface plasmon resonance (SPR), and molecular docking simulation. The results showed that hypericin was a high potential reversible and competitive α-glucosidase inhibitor, with a maximum half inhibitory concentration (IC₅₀) of 4.66 ± 0.27 mg/L. The binding affinities of hypericin with α-glucosidase were assessed using an SPR detection system, which indicated that these were strong and fast, with balances dissociation constant (KD) values of 6.56 × 10⁻⁵ M and exhibited a slow dissociation reaction. Analysis by molecular docking further revealed that hydrophobic forces are generated by interactions between hypericin and amino acid residues Arg-315 and Tyr-316. In addition, hydrogen bonding occurred between hypericin and α-glucosidase amino acid residues Lys-156, Ser-157, Gly-160, Ser-240, His-280, Asp-242, and Asp-307. The structure and micro-environment of α-glucosidase enzymes were altered, which led to a decrease in α-glucosidase activity. This research identified that hypericin, an anthracene ketone compound, could be a novel α-glucosidase inhibitor and further applied to the development of potential anti-diabetic drugs.     

Catalytic Performance of Cobalt(II) Polyethylene Catalysts with Sterically Hindered Dibenzopyranyl Substituents Studied by Experimental and MLR Methods

Given the great importance of cobalt catalysts supported by benchmark bis(imino)pyridine in the (oligo)polymerization, a series of dibenzopyran-incorporated symmetrical 2,6-bis(imino) pyridyl cobalt complexes (Co1–Co5) are designed and prepared using a one-pot template approach. The structures of the resulting complexes are well characterized by a number of techniques. After activation with either methylaluminoxane (MAO) or modified MAO (MMAO), the complexes Co1–Co4 are highly active for ethylene polymerization with a maximum activity of up to 7.36 × 10⁶ g (PE) mol⁻¹ (Co) h⁻¹ and produced highly linear polyethylene with narrow molecular weight distributions, while Co5 is completely inactive under the standard conditions. Particularly, complex Co3 affords polyethylene with high molecular weights of 85.02 and 79.85 kg mol⁻¹ in the presence of MAO and MMAO, respectively. The ¹H and ¹³C NMR spectroscopy revealed the existence of vinyl end groups in the resulting polyethylene, highlighting the predominant involvement of the β-H elimination reaction in the chain-termination process. To investigate the mechanism underlying the variation of catalytic activities as a function of substituents, multiple linear regression (MLR) analysis was performed, showing the key role of open cone angle (θ) and effective net charge (Q) on catalytic activity.     

Neutrophil Immunomodulatory Activity of (−)-Borneol,a Major Component of Essential Oils Extracted from Grindelia squarrosa

Grindelia squarrosa (Pursh) Dunal is used in traditional medicine for treating various diseases; however, little is known about the immunomodulatory activity of essential oils from this plant. Thus, we isolated essential oils from the flowers (GEO_Fl) and leaves (GEO_Lv) of G. squarrosa and evaluated the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of these essential oils revealed that the main components were α-pinene (24.7 and 23.2% in GEO_Fl and GEO_Lv, respectively), limonene (10.0 and 14.7%), borneol (23.4 and 16.6%), p-cymen-8-ol (6.1 and 5.8%), β-pinene (4.0 and 3.8%), bornyl acetate (3.0 and 5.1%), trans-pinocarveol (4.2 and 3.7%), spathulenol (3.0 and 2.0%), myrtenol (2.5 and 1.7%), and terpinolene (1.7 and 2.0%). Enantiomer analysis showed that α-pinene, β-pinene, and borneol were present primarily as (−)-enantiomers (100% enantiomeric excess (ee) for (−)-α-pinene and (−)-borneol in both GEO_Fl and GEO_Lv; 82 and 78% ee for (−)-β-pinene in GEO_Fl and GEO_Lv), while limonene was present primarily as the (+)-enantiomer (94 and 96 ee in GEO_Fl and GEO_Lv). Grindelia essential oils activated human neutrophils, resulting in increased [Ca²⁺]_i (EC₅₀ = 22.3 µg/mL for GEO_Fl and 19.4 µg/mL for GEO_Lv). In addition, one of the major enantiomeric components, (−)-borneol, activated human neutrophil [Ca²⁺]_i (EC₅₀ = 28.7 ± 2.6), whereas (+)-borneol was inactive. Since these treatments activated neutrophils, we also evaluated if they were able to down-regulate neutrophil responses to subsequent agonist activation and found that treatment with Grindelia essential oils inhibited activation of these cells by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. Likewise, (−)-borneol inhibited FPR-agonist-induced Ca²⁺ influx in neutrophils. Grindelia leaf and flower essential oils, as well as (−)-borneol, also inhibited fMLF-induced chemotaxis of human neutrophils (IC₅₀ = 4.1 ± 0.8 µg/mL, 5.0 ± 1.6 µg/mL, and 5.8 ± 1.4 µM, respectively). Thus, we identified (−)-borneol as a novel modulator of human neutrophil function.     

Binding Interaction of Betulinic Acid to α-Glucosidase and Its Alleviation on Postprandial Hyperglycemia

Inhibiting the intestinal α-glucosidase can effectively control postprandial hyperglycemia for type 2 diabetes mellitus (T2DM) treatment. In the present study, we reported the binding interaction of betulinic acid (BA), a pentacyclic triterpene widely distributed in nature, on α-glucosidase and its alleviation on postprandial hyperglycemia. BA was verified to exhibit a strong inhibitory effect against α-glucosidase with an IC₅₀ value of 16.83 ± 1.16 μM. More importantly, it showed a synergistically inhibitory effect with acarbose. The underlying inhibitory mechanism was investigated by kinetics analysis, surface plasmon resonance (SPR) detection, molecular docking, molecular dynamics (MD) simulation and binding free energy calculation. BA showed a non-competitive inhibition on α-glucosidase. SPR revealed that it had a strong and fast affinity to α-glucosidase with an equilibrium dissociation constant (K_D) value of 5.529 × 10⁻⁵ M and a slow dissociation. Molecular docking and MD simulation revealed that BA bound to the active site of α-glucosidase mainly due to the van der Waals force and hydrogen bond, and then changed the micro-environment and secondary structure of α-glucosidase. Free energy decomposition indicated amino acid residues such as PHE155, PHE175, HIE277, PHE298, GLU302, TRY311 and ASP347 of α-glucosidase at the binding pocket had strong interactions with BA, while LYS153, ARG210, ARG310, ARG354 and ARG437 showed a negative contribution to binding affinity between BA and α-glucosidase. Significantly, oral administration of BA alleviated the postprandial blood glucose fluctuations in mice. This work may provide new insights into the utilization of BA as a functional food and natural medicine for the control of postprandial hyperglycemia.     

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by ¹H-NMR, ¹³C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC₅₀ value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC₅₀ value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC₅₀ = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.     

Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis,Characterisation and Application in Rhodium-Catalysed Hydroformylation

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)₂(acac), was attested by ³¹P NMR, which presented a doublet in the range of δ = 120 ppm, with a ¹J(¹⁰³Rh-³¹P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm⁻¹ and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.     

Dielectric Properties Investigation of Metal–Insulator–Metal (MIM) Capacitors

This study presents the construction and dielectric properties investigation of atomic-layer-deposition Al₂O₃/TiO₂/HfO₂ dielectric-film-based metal–insulator–metal (MIM) capacitors. The influence of the dielectric layer material and thickness on the performance of MIM capacitors are also systematically investigated. The morphology and surface roughness of dielectric films for different materials and thicknesses are analyzed via atomic force microscopy (AFM). Among them, the 25 nm Al₂O₃-based dielectric capacitor exhibits superior comprehensive electrical performance, including a high capacitance density of 7.89 fF·µm⁻², desirable breakdown voltage and leakage current of about 12 V and 1.4 × 10⁻¹⁰ A·cm⁻², and quadratic voltage coefficient of 303.6 ppm·V⁻². Simultaneously, the fabricated capacitor indicates desirable stability in terms of frequency and bias voltage (at 1 MHz), with the corresponding slight capacitance density variation of about 0.52 fF·µm⁻² and 0.25 fF·µm⁻². Furthermore, the mechanism of the variation in capacitance density and leakage current might be attributed to the Poole–Frenkel emission and charge-trapping effect of the high-k materials. All these results indicate potential applications in integrated passive devices.