Salvia officinalis L. from Italy: A Comparative Chemical and Biological Study of Its Essential Oil in the Mediterranean Context

Salvia officinalis L. (sage) is one of the most appreciated plants for its plethora of biologically active compounds. The objective of our research was a comparative study, in the Mediterranean context, of chemical composition, anticholinesterases, and antioxidant properties of essential oils (EOs) from sage collected in three areas (S1–S3) of Southern Italy. EOs were extracted by hydrodistillation and analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory properties were investigated by employing Ellman’s method. Four in vitro assays, namely, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric-reducing ability power (FRAP), and β-carotene bleaching tests, were used to study the antioxidant effects. Camphor (16.16–18.92%), 1,8-cineole (8.80–9.86%), β-pinene (3.08–9.14%), camphene (6.27–8.08%), and α-thujone (1.17–9.26%) are identified as the most abundant constituents. However, the content of these constituents varied depending on environmental factors and pedoclimatic conditions. Principal component analysis (PCA) was performed. Based on Relative Antioxidant Capacity Index (RACI), S2 essential oil exhibited the highest radical potential with an IC₅₀ value of 20.64 μg/mL in ABTS test and presented the highest protection of lipid peroxidation with IC₅₀ values of 38.06 and 46.32 μg/mL after 30 and 60 min of incubation, respectively. The most promising inhibitory activity against BChE was found for S3 sample (IC₅₀ of 33.13 μg/mL).     

Concentration of Bioactive Phenolic Compounds in Olive Mill Wastewater by Direct Contact Membrane Distillation

Olive mill wastewater (OMW), generated as a by-product of olive oil production, is considered one of the most polluting effluents produced by the agro-food industry, due to its high concentration of organic matter and nutrients. However, OMW is rich in several polyphenols, representing compounds with remarkable biological properties. This study aimed to analyze the chemical profile as well as the antioxidant and anti-obesity properties of concentrated fractions obtained from microfiltered OMW treated by direct contact membrane distillation (DCMD). Ultra-high performance liquid chromatography (UHPLC) analyses were applied to quantify some phenols selected as phytochemical markers. Moreover, α-Amylase, α-glucosidase, and lipase inhibitory activity were investigated together with the antioxidant activity by means of assays, namely β-carotene bleaching, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic) acid (ABTS) diammonium salts, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and Ferric Reducing Activity Power (FRAP) tests. MD retentate—which has content of about five times greater of hydroxytyrosol and verbascoside and about 7 times greater of oleuropein than the feed—was more active as an antioxidant in all applied assays. Of interest is the result obtained in the DPPH test (an inhibitory concentration 50% (IC₅₀) of 9.8 μg/mL in comparison to the feed (IC₅₀ of 97.2 μg/mL)) and in the ABTS assay (an IC₅₀ of 0.4 μg/mL in comparison to the feed (IC₅₀ of 1.2 μg/mL)).     

Carbohydrate Hydrolase-Inhibitory Activity of Juice-Based Phenolic Extracts in Correlation to Their Anthocyanin/Copigment Profile

Red fruits and their juices are rich sources of polyphenols, especially anthocyanins. Some studies have shown that such polyphenols can inhibit enzymes of the carbohydrate metabolism, such as α-amylase and α-glucosidase, that indirectly regulate blood sugar levels. The presented study examined the in vitro inhibitory activity against α-amylase and α-glucosidase of various phenolic extracts prepared from direct juices, concentrates, and purees of nine different berries which differ in their anthocyanin and copigment profile. Generally, the extracts with the highest phenolic content—aronia (67.7 ± 3.2 g GAE/100 g; cyanidin 3-galactoside; chlorogenic acid), pomegranate (65.7 ± 7.9 g GAE/100 g; cyanidin 3,5-diglucoside; punicalin), and red grape (59.6 ± 2.5 g GAE/100 g; malvidin 3-glucoside; quercetin 3-glucuronide)—showed also one of the highest inhibitory activities against α-amylase (326.9 ± 75.8 μg/mL; 789.7 ± 220.9 μg/mL; 646.1 ± 81.8 μg/mL) and α-glucosidase (115.6 ± 32.5 μg/mL; 127.8 ± 20.1 μg/mL; 160.6 ± 68.4 μg/mL) and, partially, were even more potent inhibitors than acarbose (441 ± 30 μg/mL; 1439 ± 85 μg/mL). Additionally, the investigation of single anthocyanins and glycosylated flavonoids demonstrated a structure- and size-dependent inhibitory activity. In the future in vivo studies are envisaged.     

Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)

In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C₁₃-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6′-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC₅₀ 3.4 ± 0.2 μM) compared to the reference standard acarbose (IC₅₀ 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 μM, compared to acarbose (IC₅₀ 665 ± 42 μM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC₅₀ of 94.7 ± 1.3 and 85.3 ± 2.4 μM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC₅₀ > 100 μM).     

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.     

Pyridine substituted BODIPYs: synthesis,characterization and cholinesterease, α-glucosidase inhibitory,DNA hydrolytic cleavage effects

In this study, the synthesis of new monostyryl (BDPY-2) and distyryl BODIPY dyes (BDPY-4, BDPY-5) containing pyridine groups has been reported for the first time. The acetylcholinesterase from Electrophorus electricus (AChE), butyrylcholinesterase from equine serum (BuChE), α-glucosidase from Saccharomyces cerevisiae and DNA hydrolytic cleavage actions of BDPY-2, BDPY-4, BDPY-5 were investigated using various techniques. The results indicated that the compounds had varying inhibition properties against AChE, BuChE, and α-glucosidase. BDPY-4 was the most potent compound on AChE with IC₅₀ of 54.78 ± 4.51 µM, and Lineweaver–Burk plots indicated that the compound is bound to a site other than the active site as a noncompetitive inhibitor. The compound-protein binding experiment showed that BDPY-4 changed the microenvironment around AChE. On the other hand, the compounds showed lower α-glucosidase inhibition than the positive control. The DNA hydrolytic cleavage effects were not observed on supercoiled plasmid DNA in the presence of the compounds as compared to negative controls. These findings suggested that BDPY-4 might be a promising compound to treat Alzheimer’s diseases.     

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.     

Quantification of Major Bioactive Constituents,Antioxidant Activity,and Enzyme Inhibitory Effects of Whole Coffee Cherries (Coffea arabica) and Their Extracts

Coffee cherry is a rich source of chlorogenic acids (CGAs) and caffeine. In this study we examined the potential antioxidant activity and enzyme inhibitory effects of whole coffee cherries (WCC) and their two extracts on α-amylase, α-glucosidase and acetylcholinesterase (AChE) activities, which are targets for the control of diabetes and Alzheimer’s diseases. Whole coffee cherry extract 40% (WCCE1) is rich in chlorogenic acid compounds, consisting of a minimum of 40% major isomers, namely 3-caffeoylquinic acids, 4-caffeoylquinic acids, 5-caffeoylquinic acids, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, 4-feruloylquinc acid, and 5-feruloylquinc acid. Whole coffee cherry extract 70% (WCCE2) is rich in caffeine, with a minimum of 70%. WCCE1 inhibited the activities of digestive enzymes α-amylase and α-glucosidase, and WCCE2 inhibited acetylcholinesterase activities with their IC₅₀ values of 1.74, 2.42, and 0.09 mg/mL, respectively. Multiple antioxidant assays—including DPPH, ABTS, FRAP, ORAC, HORAC, NORAC, and SORAC—demonstrated that WCCE1 has strong antioxidant activity.     

Structural and Biological Properties of Water Soluble Polysaccharides from Lotus Leaves: Effects of Drying Techniques

In the present study, the influence of five drying techniques on the structural and biological properties of polysaccharides from lotus leaves (LLPs) was investigated. Results revealed that the yields, contents of basic chemical components, molecular weights, and molar ratios of compositional monosaccharides of LLPs varied by different drying technologies. Low molecular weight distributions were observed in polysaccharides obtained from lotus leaves by hot air drying (LLP-H), microwave drying (LLP-M), and radio frequency drying (LLP-RF), respectively. The high contents of bound polyphenolics were measured in LLP-H and LLP-M, as well as polysaccharides obtained from lotus leaves by vacuum drying (LLP-V). Furthermore, both Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectra of LLPs were similar, indicating that drying technologies did not change their basic chemical structures. Besides, all LLPs exhibited obvious biological properties, including in vitro antioxidant capacities, antiglycation activities, and inhibitory effects on α-glucosidase. Indeed, LLP-H exhibited higher 2,2-azidobisphenol (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging ability (IC₅₀ values, LLP-H, 0.176 ± 0.004 mg/mL; vitamin C, 0.043 ± 0.002 mg/mL) and 2,2-diphenyl-1-(2,4,6-trinitrate phenyl) hydrazine radical scavenging ability (IC₅₀ values, LLP-H, 0.241 ± 0.007 mg/mL; butylated hydroxytoluene, 0.366 ± 0.010 mg/mL) than others, and LLP-M exerted stronger antiglycation (IC₅₀ values, LLP-M, 1.023 ± 0.053 mg/mL; aminoguanidine, 1.744 ± 0.080 mg/mL) and inhibitory effects on α-glucosidase (IC₅₀ values, LLP-M, 1.90 ± 0.02 μg/mL; acarbose, 724.98 ± 16.93 μg/mL) than others. These findings indicate that both hot air drying and microwave drying can be potential drying techniques for the pre-processing of lotus leaves for industrial applications.     

LC-HRMS Profiling and Antidiabetic,Anticholinergic, and Antioxidant Activities of Aerial Parts of Kınkor (Ferulago stellata)

Kınkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kınkor (Ferulago stellata), some putative antioxidant methods such as DPPH· scavenging activity, ABTS^•+ scavenging activity, ferric ions (Fe³⁺) reduction method, cupric ions (Cu²⁺) reducing capacity, and ferrous ions (Fe²⁺)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and α-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kınkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kınkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kınkor (Ferulago stellata) demonstrated IC₅₀ values of 1.772 μg/mL against acetylcholinesterase (AChE), 33.56 ± 2.96 μg/mL against α-glycosidase, and 0.639 μg/mL against α-amylase enzyme respectively.     

New Multifunctional Agents Based on Conjugates of 4-Amino-2,3-polymethylenequinoline and Butylated Hydroxytoluene for Alzheimer’s Disease Treatment

New hybrids of 4-amino-2,3-polymethylenequinoline with different sizes of the aliphatic ring linked to butylated hydroxytoluene (BHT) by enaminoalkyl (7) or aminoalkyl (8) spacers were synthesized as potential multifunctional agents for Alzheimer’s disease (AD) treatment. All compounds were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. Lead compound 8c, 2,6-di-tert-butyl-4-{[2-(7,8,9,10- tetrahydro-6H-cyclohepta[b]quinolin-11-ylamino)-ethylimino]-methyl}-phenol exhibited an IC₅₀(AChE) = 1.90 ± 0.16 µM, IC₅₀(BChE) = 0.084 ± 0.008 µM, and 13.6 ± 1.2% propidium displacement at 20 μM. Compounds possessed low activity against carboxylesterase, indicating likely absence of clinically unwanted drug-drug interactions. Kinetics were consistent with mixed-type reversible inhibition of both cholinesterases. Docking indicated binding to catalytic and peripheral AChE sites; peripheral site binding along with propidium displacement suggest the potential of the hybrids to block AChE-induced β-amyloid aggregation, a disease-modifying effect. Compounds demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Conjugates 8 with amine-containing spacers were better antioxidants than those with enamine spacers 7. Computational ADMET profiles for all compounds predicted good blood-brain barrier distribution (permeability), good intestinal absorption, and medium cardiac toxicity risk. Overall, based on their favorable pharmacological and ADMET profiles, conjugates 8 appear promising as candidates for AD therapeutics.     

Outlining In Vitro and In Silico Cholinesterase Inhibitory Activity of Twenty-Four Natural Products of Various Chemical Classes: Smilagenin,Kokusaginine, and Methyl Rosmarinate as Emboldening Inhibitors

Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer’s disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemical classes (i.e., diosgenin, hecogenin, rockogenin, smilagenin, tigogenin, astrasieversianins II and X, astragalosides I, IV, and VI, cyclocanthosides E and G, macrophyllosaponins A-D, kokusaginin, lamiide, forsythoside B, verbascoside, alyssonoside, ipolamide, methyl rosmarinate, and luteolin-7-O-glucuronide) was examined using ELISA microtiter assay. Among them, only smilagenin and kokusaginine displayed inhibitory action against AChE (IC₅₀ = 43.29 ± 1.38 and 70.24 ± 2.87 µg/mL, respectively). BChE was inhibited by only methyl rosmarinate and kokusaginine (IC₅₀ = 41.46 ± 2.83 and 61.40 ± 3.67 µg/mL, respectively). IC₅₀ values for galantamine as the reference drug were 1.33 ± 0.11 µg/mL for AChE and 52.31 ± 3.04 µg/mL for BChE. Molecular docking experiments showed that the orientation of smilagenin and kokusaginine was mainly driven by the interactions with the peripheral anionic site (PAS) comprising residues of hAChE, while kokusaginine and methyl rosmarinate were able to access deeper into the active gorge in hBChE. Our data indicate that similagenin, kokusaginine, and methyl rosmarinate could be hit compounds for designing novel anti-Alzheimer agents.     

Phytochemical Profile,Antioxidant Capacity, α-Amylase and α-Glucosidase Inhibitory Potential of Wild Moroccan Inula viscosa (L.) Aiton Leaves

Medicinal plants offer imperative sources of innovative chemical substances with important potential therapeutic effects. Among them, the members of the genus Inula have been widely used in traditional medicine for the treatment of several diseases. The present study investigated the antioxidant (DPPH, ABTS and FRAP assays) and the in vitro anti-hyperglycemic potential of aerial parts of Inula viscosa (L.) Aiton (I. viscosa) extracts through the inhibition of digestive enzymes (α-amylase and α-glucosidase), responsible of the digestion of poly and oligosaccharides. The polyphenolic profile of the Inula viscosa (L.) Aiton EtOAc extract was also investigated using HPLC-DAD/ESI-MS analysis, whereas the volatile composition was elucidated by GC-MS. The chemical analysis resulted in the detection of twenty-one polyphenolic compounds, whereas the volatile profile highlighted the occurrence of forty-eight different compounds. Inula viscosa (L.) Aiton presented values as high as 87.2 ± 0.50 mg GAE/g and 78.6 ± 0.55mg CE/g, for gallic acid and catechin, respectively. The EtOAc extract exhibited the higher antioxidant activity compared to methanol and chloroform extracts in different tests with (IC₅₀ = 0.6 ± 0.03 µg/mL; IC₅₀ = 8.6 ± 0.08 µg/mL; 634.8 mg ± 1.45 AAE/g extract) in DPPH, ABTS and FRAP tests. Moreover, Inula viscosa (L.) Aiton leaves did show an important inhibitory effect against α-amylase and α-glucosidase. On the basis of the results achieved, such a species represents a promising traditional medicine, thanks to its remarkable content of functional bioactive compounds, thus opening new prospects for research and innovative phytopharmaceuticals developments.     

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC₅₀ = 0.22 and 0.12 μM) and moderately inhibited DPP-4 (IC₅₀ = 23.59 and 26.19 μM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 μM being comparable to that of metformin at a concentration of 1 mM.     

Phytochemical Composition,Antioxidant Activity,and Enzyme Inhibitory Activities (α-Glucosidase,Xanthine Oxidase,and Acetylcholinesterase) of Musella lasiocarpa

In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their α-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH· scavenging ability, ABTS·⁺ scavenging ability, and α-glucosidase inhibitory activity with the IC₅₀ values of 22.17, 12.10, and 125.66 μg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO₄/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC₅₀ = 10.11 μg/mL), and the best xanthine oxidase inhibitory ability (IC₅₀ = 5.23 μg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 μg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications.     

Water Extract of Mungbean (Vigna radiata L.) Inhibits Protein Tyrosine Phosphatase-1B in Insulin-Resistant HepG2 Cells

The present study aimed to investigate the effects of mungbean water extract (MWE) on insulin downstream signaling in insulin-resistant HepG2 cells. Whole seed mungbean was extracted using boiling water, mimicking a traditional cooking method. Vitexin and isovitexin were identified in MWE. The results showed that MWE inhibited protein tyrosine phosphatase (PTP)-1B (IC₅₀ = 10 μg/mL), a negative regulator of insulin signaling. MWE enhanced cellular glucose uptake and altered expression of genes involved in glucose metabolism, including forkhead box O1 (FOXO1), phosphoenolpyruvate carboxykinase (PEPCK), and glycogen synthase kinase (GSK)-3β in the insulin-resistant HepG2 cells. In addition, MWE inhibited both α-amylase (IC₅₀ = 36.65 mg/mL) and α-glucosidase (IC₅₀ = 3.07 mg/mL). MWE also inhibited the formation of advanced glycation end products (AGEs) (IC₅₀ = 2.28 mg/mL). This is the first study to show that mungbean water extract increased cellular glucose uptake and improved insulin sensitivity of insulin-resistant HepG2 cells through PTP-1B inhibition and modulating the expression of genes related to glucose metabolism. This suggests that mungbean water extract has the potential to be a functional ingredient for diabetes.     

Chromatographic Separation of Breynia retusa (Dennst.) Alston Bark,Fruit and Leaf Constituents from Bioactive Extracts

Breynia retusa (Dennst.) Alston (also known as Cup Saucer plant) is a food plant with wide applications in traditional medicine, particularly in Ayurveda. Extracts obtained with four solvents (dichloromethane, methanol, ethyl acetate and water), from three plant parts, (fruit, leaf and bark) were obtained. Extracts were tested for total phenolic, flavonoid content and antioxidant activities using a battery of assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum) and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase as target enzymes. Results showed that the methanolic bark extract exhibited significant radical scavenging activity (DPPH: 202.09 ± 0.15; ABTS: 490.12 ± 0.18 mg Trolox equivalent (TE)/g), reducing potential (FRAP: 325.86 ± 4.36: CUPRAC: 661.82 ± 0.40 mg TE/g) and possessed the highest TAC (3.33 ± 0.13 mmol TE/g). The methanolic extracts were subjected to LC-DAD-MSⁿ and NMR analysis. A two-column LC method was developed to separate constituents, allowing to identify and quantify forty-four and fifteen constituents in bark and fruits, respectively. Main compound in bark was epicatechin-3-O-sulphate and isolation of compound was performed to confirm its identity. Bark extract contained catechins, procyanidins, gallic acid derivatives and the sulfur containing spiroketal named breynins. Aerial parts mostly contained flavonoid glycosides. Considering the bioassays, the methanolic bark extract resulted a potent tyrosinase (152.79 ± 0.27 mg kojic acid equivalent/g), α-amylase (0.99 ± 0.01 mmol acarbose equivalent ACAE/g) and α-glucosidase (2.16 ± 0.01 mmol ACAE/g) inhibitor. In conclusion, methanol is able to extract the efficiently the phytoconstituents of B. retusa and the bark is the most valuable source of compounds.     

Antioxidant and Starch-Hydrolyzing Enzymes Inhibitory Properties of Striga-Resistant Yellow-Orange Maize Hybrids

Most of the health benefits derived from cereals are attributed to their bioactive compounds. This study evaluated the levels of the bioactive compounds, and the antioxidant and starch-hydrolyzing enzymes inhibitory properties of six pipeline Striga-resistant yellow-orange maize hybrids (coded AS1828-1, 4, 6, 8, 9, 11) in vitro. The maize hybrids were grown at the International Institute of Tropical Agriculture (IITA), Nigeria. The bioactive compounds (total phenolics, tannins, flavonoids, and phytate) levels, antioxidant (DPPH^• and ABTS^•+ scavenging capacity and reducing power) and starch-hydrolyzing enzymes (α-amylase and α-glucosidase) inhibitory activities of the maize hybrids were determined by spectrophotometry. At the same time, carotenoids were quantified using a reverse-phase HPLC system. The ranges of the bioactive compounds were: 11.25–14.14 mg GAE/g (total phenolics), 3.62–4.67 mg QE/g (total flavonoids), 3.63–6.29 mg/g (tannins), 3.66–4.31% (phytate), 8.92–12.11 µg/g (total xanthophylls), 2.42–2.89 µg/g (total β-carotene), and 3.17–3.77 µg/g (total provitamin A carotenoids). Extracts of the maize hybrids scavenged DPPH^• (SC₅₀: 9.07–26.35 mg/mL) and ABTS^•+ (2.65–7.68 TEAC mmol/g), reduced Fe³⁺ to Fe²⁺ (0.25 ± 0.64–0.43 ± 0.01 mg GAE/g), and inhibited α-amylase and α-glucosidase, with IC₅₀ ranges of 26.28–52.55 mg/mL and 47.72–63.98 mg/mL, respectively. Among the six clones of the maize hybrids, AS1828-9 had the highest (p < 0.05) levels of tannins and phytate and the strongest antioxidant and starch-hydrolyzing enzymes inhibitory activities. Significant correlations were observed between total phenolics and the following: ABTS^•+ (p < 0.01, r = 0.757), DPPH^• SC₅₀ (p < 0.01, r = −0.867), reducing power (p < 0.05, r = 0.633), α-amylase IC₅₀ (p < 0.01, r = −0.836) and α-glucosidase IC₅₀ (p < 0.05, r = −0.582). Hence, the Striga-resistant yellow-orange maize hybrids (especially AS1828-9) may be beneficial for alleviating oxidative stress and postprandial hyperglycemia.     

Chemical Constituents from the Wild Atractylodes macrocephala Koidz and Acetylcholinesterase Inhibitory Activity Evaluation as Well as Molecular Docking Study

Screening the lead compounds which could interact both with PAS and CAS of acetylcholinesterase (AChE) is an important trend in finding innovative drugs for Alzheimer’s disease (AD). In this paper, four sesquiterpenes, i.e., atractylenolide III (1), atractylenolide IV (2), 3-acetyl-atractylon (3) and β-eudesmol (4), were obtained from the wild Atractylode macrocephala grown in Qimen for the first time. Their structures were elucidated mainly by NMR spectroscopy. To screen the potential dual site inhibitors of AChE, the compounds 1, 2, 3, as well as a novel and rare bisesquiterpenoid lactone, biatractylenolide II (5), which was also obtained from the tilted plant in our previous investigation, were evaluated their AChE inhibitory activities by using Ellman’s colorimetric method. The results showed that biatractylenolide II displayed moderate inhibitory activity (IC₅₀ = 19.61 ± 1.11 μg/mL) on AChE. A further molecular docking study revealed that biatractylenolide II can interact with both the peripheral anionic site (PAS) and the catalytic active site (CAS) of AChE. These data suggest that biatractylenolide II can be considered a new lead compound to research and develop more potential dual site inhibitors of AChE.     

Asperflaloids A and B from Aspergillus flavipes DZ-3, an Endophytic Fungus of Eucommia ulmoides Oliver

The fungus strain DZ-3 was isolated from twigs of the well-known medicinal plant Eucommia ulmoides Oliver and identified as Aspergillus flavipes. Two new alkaloids, named asperflaloids A and B (1 and 2), together with 10 known compounds (3–12) were obtained from the EtOAc extract of the strain. Interestingly, the alkaloids 1–4 with different frameworks are characterized by the presence of the same anthranilic acid residue. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of asperflaloids A and B was resolved by quantum chemistry calculation. All compounds were screened for their inhibitions against α-glucosidase and the antioxidant capacities. The results were that compound 3 had an IC₅₀ value of 750.8 μM toward α-glucosidase, and the phenol compounds 7 and 8 exhibited potent antioxidant capacities with IC₅₀ values 14.4 and 27.1 μM respectively.