In Vitro Evaluation of α-amylase and α-glucosidase Inhibition of 2,3-Epoxyprocyanidin C1 and Other Constituents from Pterocarpus erinaceus Poir

Diabetes mellitus is a metabolic disorder which is one of the leading causes of mortality and morbidities in elderly humans. Chronic diabetes can lead to kidney failure, blindness, limb amputation, heart attack and stroke. Physical activity, healthy diets and medications can reduce the incidence of diabetes, so the search for more efficient antidiabetic therapies, most especially from natural products, is a necessity. Herein, extract from roots of the medicinal plant Pterocarpus erinaceus was purified by column chromatography and afforded ten compounds which were characterized by EIMS, HR-FAB-MS, 1D and 2D NMR techniques. Amongst them were, a new trimeric derivative of epicatechin, named 2,3-Epoxyprocyanidin C1 (1); two pentacyclic triterpenoids, friedelin (2) and betulin (3); angolensin (4); flavonoids such as 7-methoxygenistein (5), 7-methoxydaidzein (6), apigenin 7-O-glucoronide (8) and naringenin 7-O-β-D-glucopyranoside (9); and an ellagic acid derivative (10). The extract and compounds were evaluated for their antidiabetic potential by α-amylase and α-glucosidase inhibitory assays. IC₅₀ values of compound 7 (48.1 ± 0.9 µg/mL), compound 8 (48.6 ± 0.1 µg/mL), compound 9 (50.2 ± 0.5 µg/mL) and extract (40.5 ± 0.8 µg/mL) when compared to that of acarbose (26.4 ± 0.3 µg/mL) indicated good α-amylase inhibition. In the α-glucosidase assay, the extract (IC₅₀ = 31.2 ± 0.1 µg/mL), compound 7 (IC₅₀ = 39.5 ± 1.2 µg/mL), compound 8 (IC₅₀ = 40.9 ± 1.3 µg/mL), compound 1 (IC₅₀ = 41.6 ± 1.0 µg/mL), Compound 4 (IC₅₀ = 43.4 ± 0.5 µg/mL), compound 5 (IC₅₀ = 47.6 ± 0.9 µg/mL), compound 6 (IC₅₀ = 46.3 ± 0.2 µg/mL), compound 7 (IC₅₀ = 45.0 ± 0.8 µg/mL), compound 9 (IC₅₀ = 44.8 ± 0.6 µg/mL) and compound 11 (IC₅₀ = 47.5 ± 0.4 µg/mL) all had moderate-to-good inhibitions, compared to acarbose (IC₅₀ = 22.0 ± 0.5 µg/mL). The ability to inhibit α-amylase and α-glucosidase indicates that P. erinaceus and its compounds can lower blood glucose levels by delaying hydrolysis of carbohydrates into sugars, thereby providing a source of natural antidiabetic remedy.     

Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.

Englerophytum magalismontanum, a medicinal plant with ethnopharmacology use, has a dearth of information regarding its antidiabetic properties. This study evaluated the crude methanol leaf extract of E. magalismontanum and its fractions for total phenolic content, antioxidant activity, and digestive enzymes (α-amylase and α-glucosidase) inhibitory activity using standard methods. The total phenolic content (56.53 ± 1.94 mg GAE/g dry extract) and DPPH Trolox antioxidant equivalent (TAE) (1.51 ± 0.66 µg/mL) of the methanol fraction were the highest among the fractions. The IC₅₀ values of the methanol fraction against α-amylase (10.76 ± 1.33 µg/mL) and α-glucosidase (12.25 ± 1.05 µg/mL) activities were also high. Being the most active, the methanol fraction was subjected to bio-assay guided column chromatography-based enzyme inhibition to obtain a pure compound. The phenolic compound isolated and identified as naringenin inhibited α-amylase and α-glucosidase with IC₅₀ of 5.81 ± 2.14 µg/mL and 4.77 ± 2.99 µg/mL, respectively. This is the first study to isolate naringenin from E. magalismontanum extract. The molecular docking and molecular dynamics studies demonstrated naringenin as a promising lead compound in comparison to acarbose for the treatment of diabetes through the inhibition of α-glucosidase activity.     

Hypoglycemic and Antioxidant Properties of Extracts and Fractions from Polygoni Avicularis Herba

Our research focused on the hypoglycemic capability and the possible mechanisms of extract and fractions from Polygoni Avicularis Herba (PAH) based on α-glucosidase, α-amylase inhibition assays, glucose uptake experiment, HPLC-MS analysis, and molecular docking experiment. In addition, DPPH, ABTS, and FRAP assays were used for determining the antioxidant capability. The results of total flavonoids and phenolics contents showed that ethyl acetate fraction (EAF) possessed the highest flavonoids and phenolics with values of 159.7 ± 2.5 mg rutin equivalents/g and 107.6 ± 2.0 mg galic acid equivalents/g, respectively. The results of in vitro hypoglycemic activity showed that all samples had effective α-glucosidase inhibition capacities, and EAF possessed the best inhibitory effect with IC₅₀ value of 1.58 ± 0.24 μg/mL. In addition, n-butanol fraction (NBF) significantly promoted the glucose uptake rate of 3T3-L1 adipocytes. HPLC-MS analysis and molecular docking results proved the interactions between candidates and α-glucosidase. The results of antioxidation capacities showed that EAF possessed the best antioxidation abilities with DPPH, ABTS, and FRAP. In summary, the hypoglycemic activity of PAH might be related to the inhibition of α-glucosidase (EAF > PEF > NBF) and the promotion of glucose uptake in 3T3-L1 adipocytes (NBF). Simultaneously, the antioxidation capacity of PAH might be related to the abundant contents of flavonoids and other phenolics (EAF > PEF > NBF).     

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.     

LC-MS/MS-Based Metabolomic Profiling of Constituents from Glochidion velutinum and Its Activity against Cancer Cell Lines

This study aimed to establish the phytochemical profile of Glochidion velutinum and its cytotoxic activity against prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. The phytochemical composition of G. velutinum leaf extract and its fractions was established with the help of total phenolic and flavonoid contents and LC-MS/MS-based metabolomics analysis. The crude methanolic extract and its fractions were studied for pharmacological activity against PC-3 and MCF-7 cell lines using the MTT assay. The total phenolic content of the crude extract and its fractions ranged from 44 to 859 µg GAE/mg of sample whereas total flavonoid contents ranged from 20 to 315 µg QE/mg of sample. A total of forty-eight compounds were tentatively dereplicated in the extract and its fractions. These phytochemicals included benzoic acid derivatives, flavans, flavones, O-methylated flavonoids, flavonoid O- and C-glycosides, pyranocoumarins, hydrolysable tannins, carbohydrate conjugates, fatty acids, coumarin glycosides, monoterpenoids, diterpenoids, and terpene glycosides. The crude extract (IC₅₀ = 89 µg/mL), the chloroform fraction (IC₅₀ = 27 µg/mL), and the water fraction (IC₅₀ = 36 µg/mL) were found to be active against the PC-3 cell line. However, the crude extract (IC₅₀ = 431 µg/mL), the chloroform fraction (IC₅₀ = 222 µg/mL), and the ethyl acetate fraction (IC₅₀ = 226 µg/mL) have shown prominent activity against breast cancer cells. Moreover, G. velutinum extract and its fractions presented negligible toxicity to normal macrophages at the maximum tested dose (600 µg/mL). Among the compounds identified through LC-MS/MS-based metabolomics analysis, epigallocatechin gallate, ellagic acid, isovitexin, and rutin were reported to have anticancer activity against both prostate and breast cancer cell lines and might be responsible for the cytotoxic activities of G. velutinum extract and its bioactive fractions.     

Identification of α-Glucosidase Inhibitors from Scutellaria edelbergii: ESI-LC-MS and Computational Approach

The recent study investigated the in vitro anti-diabetic impact of the crude extract (MeOH) and subfractions ethyl acetate (EtOAc); chloroform; n-butanol; n-hexane; and aqueous fraction of S. edelbergii and processed the active EtOAc fraction for the identification of chemical constituents for the first time via ESI-LC-MS analysis through positive ionization mode (PIM) and negative ionization mode (NIM); the identified compounds were further validated through computational analysis via standard approaches. The crude extract and subfractions presented appreciable activity against the α-glucosidase inhibitory assay. However, the EtOAc fraction with IC₅₀ = 0.14 ± 0.06 µg/mL revealed the maximum potential among the fractions used, followed by the MeOH and n-hexane extract with IC₅₀ = 1.47 ± 0.14 and 2.18 ± 0.30 µg/mL, respectively. Moreover, the acarbose showed an IC₅₀ = 377.26 ± 1.20 µg/ mL whereas the least inhibition was observed for the chloroform fraction, with an IC₅₀ = 23.97 ± 0.14 µg/mL. Due to the significance of the EtOAc fraction, when profiled for its chemical constituents, it presented 16 compounds among which the flavonoid class was dominant, and offered eight compounds, of which six were identified in NIM, and two compounds in PIM. Moreover, five terpenoids were identified—three and two in NIM and PIM, respectively—as well as two alkaloids, both of which were detected in PIM. The EtOAc fraction also contained one phenol that was noticed in PIM. The detected flavonoids, terpenoids, alkaloids, and phenols are well-known for their diverse biomedical applications. The potent EtOAc fraction was submitted to computational analysis for further validation of α-glucosidase significance to profile the responsible compounds. The pharmacokinetic estimations and protein-ligand molecular docking results with the support of molecular dynamic simulation trajectories at 100 ns suggested that two bioactive compounds—dihydrocatalpol and leucosceptoside A—from the EtOAc fraction presented excellent drug-like properties and stable conformations; hence, these bioactive compounds could be potential inhibitors of alpha-glucosidase enzyme based on intermolecular interactions with significant residues, docking score, and binding free energy estimation. The stated findings reflect that S. edelbergii is a rich source of bioactive compounds offering potential cures for diabetes mellitus; in particular, dihydrocatalpol and leucosceptoside A could be excellent therapeutic options for the progress of novel drugs to overcome diabetes mellitus.     

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.     

Phytochemical Composition and In Vitro Antioxidant,Anti-Inflammatory,Anticancer, and Enzyme-Inhibitory Activities of Artemisia nilagirica (C.B. Clarke) Pamp

Plants have been employed in therapeutic applications against various infectious and chronic diseases from ancient times. Various traditional medicines and folk systems have utilized numerous plants and plant products, which act as sources of drug candidates for modern medicine. Artemisia is a genus of the Asteraceae family with more than 500 species; however, many of these species are less explored for their biological efficacy, and several others are lacking scientific explanations for their uses. Artemisia nilagirica is a plant that is widely found in the Western Ghats, Kerala, India and is a prominent member of the genus. In the current study, the phytochemical composition and the antioxidant, enzyme-inhibitory, anti-inflammatory, and anticancer activities were examined. The results indicated that the ethanol extract of A. nilagirica indicated in vitro DPPH scavenging (23.12 ± 1.28 µg/mL), ABTS scavenging (27.44 ± 1.88 µg/mL), H₂O₂ scavenging (12.92 ± 1.05 µg/mL), and FRAP (5.42 ± 0.19 µg/mL). The anti-inflammatory effect was also noticed in the Raw 264.7 macrophages, where pretreatment with the extract reduced the LPS-stimulated production of cytokines (p < 0.05). A. nilagirica was also efficient in inhibiting the activities of α-amylase (38.42 ± 2.71 µg/mL), α-glucosidase (55.31 ± 2.16 µg/mL), aldose reductase (17.42 ± 0.87 µg/mL), and sorbitol dehydrogenase (29.57 ± 1.46 µg/mL). It also induced significant inhibition of proliferation in breast (MCF7 IC₅₀ = 41.79 ± 1.07, MDAMB231 IC₅₀ = 55.37 ± 2.11µg/mL) and colon (49.57 ± 1.46 µg/mL) cancer cells. The results of the phytochemical screening indicated a higher level of polyphenols and flavonoids in the extract and the LCMS analysis revealed the presence of various bioactive constituents including artemisinin.     

Synthesis of Novel N-Methylmorpholine-Substituted Benzimidazolium Salts as Potential α-Glucosidase Inhibitors

The α-glucosidase enzyme, located in the brush border of the small intestine, is responsible for overall glycemic control in the body. It hydrolyses the 1,4-linkage in the carbohydrates to form blood-absorbable monosaccharides that ultimately increase the blood glucose level. α-Glucosidase inhibitors (AGIs) can reduce hydrolytic activity and help to control type 2 diabetes. Aiming to achieve this, a novel series of 1-benzyl-3-((2-substitutedphenyl)amino)-2-oxoethyl)-2-(morpholinomethyl)-1H-benzimidazol-3-ium chloride was synthesized and screened for its α-glucosidase inhibitory potential. Compounds 5d, 5f, 5g, 5h and 5k exhibited better α-glucosidase inhibitions compared to the standard drug (acarbose IC₅₀ = 58.8 ± 0.012 µM) with IC₅₀ values of 15 ± 0.030, 19 ± 0.060, 25 ± 0.106, 21 ± 0.07 and 26 ± 0.035 µM, respectively. Furthermore, the molecular docking studies explored the mechanism of enzyme inhibitions by different 1,2,3-trisubstituted benzimidazolium salts via significant ligand–receptor interactions.     

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.     

In Vitro Inhibitory Effects of Viburnum opulus Bark and Flower Extracts on Digestion of Potato Starch and Carbohydrate Hydrolases Activity

One of the effective treatments for diabetes is to reduce and delay the absorption of glucose by inhibition of α-amylase and α-glucosidase in the digestive tract. Currently, there is a great interest in natural inhibitors from various part of plants. In the present study, the phenolic compounds composition of V. opulus bark and flower, and their inhibitory effects on in vitro potato starch digestion as well as on α-amylase and α-glucosidase, have been studied. Bark and flower phenolic extracts reduced the amount of glucose released from potato starch during tree-stage simulated digestion, with IC₅₀ value equal to 87.77 µg/mL and 148.87 µg/mL, respectively. Phenolic bark extract showed 34.9% and 38.4% more potent inhibitory activity against α-amylase and α-glucosidase, respectively, but the activity of plant extracts was lower than that of acarbose. Chlorogenic acid (27.26% of total phenolics) and (+)-catechin (30.48% of total phenolics) were the most prominent phenolics in the flower and bark extracts, respectively. Procyanidins may be responsible for the strongest V. opulus bark inhibitory activity against α-amylase, while (+)-catechin relative to α-glucosidase. This preliminary study provides the basis of further examination of the suitability of V. opulus bark compounds as components of nutraceuticals and functional foods with antidiabetic activity.     

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.     

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo,In Vitro,In Situ,and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO’s effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC₅₀ = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC₅₀ = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC₅₀ = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.     

The Glycemic Control Potential of Some Amaranthaceae Plants,with Particular Reference to In Vivo Antidiabetic Potential of Agathophora alopecuroides

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides, Anabasis lachnantha, Atriplex leucoclada, Cornulaca aucheri, Halothamnus bottae, Halothamnus iraqensis, Salicornia persia, Salsola arabica, and Salsola villosa, growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC₅₀ 117.9 µg/mL noting better activity than Acarbose (IC₅₀ 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC₅₀ 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase (p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.     

Identification of Phenolic Compounds by LC-MS/MS and Evaluation of Bioactive Properties of Two Edible Halophytes: Limonium effusum and L. sinuatum

This work aimed to evaluate the phenolic content and in vitro antioxidant, antimicrobial and enzyme inhibitory activities of the methanol extracts and their fractions of two edible halophytic Limonium species, L. effusum (LE) and L. sinuatum (LS). The total phenolic content resulted about two-fold higher in the ethyl acetate fraction of LE (522.82 ± 5.67 mg GAE/g extract) than in that of LS (274.87 ± 1.87 mg GAE/g extract). LC-MS/MS analysis indicated that tannic acid was the most abundant phenolic acid in both species (71,439.56 ± 3643.3 µg/g extract in LE and 105,453.5 ± 5328.1 µg/g extract in LS), whereas hyperoside was the most abundant flavonoid (14,006.90 ± 686.1 µg/g extract in LE and 1708.51 ± 83.6 µg/g extract in LS). The antioxidant capacity was evaluated by DPPH and TAC assays, and the stronger antioxidant activity in ethyl acetate fractions was highlighted. Both species were more active against Gram-positive bacteria than Gram negatives and showed considerable growth inhibitions against tested fungi. Interestingly, selective acetylcholinesterase (AChE) activity was observed with LE and LS. Particularly, the water fraction of LS strongly inhibited AChE (IC₅₀ = 0.199 ± 0.009 µg/mL). The ethyl acetate fractions of LE and LS, as well as the n-hexane fraction of LE, exhibited significant antityrosinase activity (IC₅₀ = 245.56 ± 3.6, 295.18 ± 10.57 and 148.27 ± 3.33 µg/mL, respectively). The ethyl acetate fraction and methanol extract of LS also significantly inhibited pancreatic lipase (IC₅₀ = 83.76 ± 4.19 and 162.2 ± 7.29 µg/mL, respectively). Taken together, these findings warrant further investigations to assess the potential of LE and LS as a bioactive source that can be exploited in pharmaceutical, cosmetics and food industries.     

Chemical Markers and Pharmacological Characters of Pelargonium graveolens Essential Oil from Palestine

Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, antioxidant, antimicrobial, metabolic, and cyclooxygenase (COX) enzymes inhibitory characteristics of P. graveolens essential oil (PGEO) from Palestine utilizing reference methods. There were 70 chemicals found in the GCMS analysis, and oxygenated terpenoids were the most abundant group of the total PGEO. Citronellol (24.44%), citronellyl formate (15.63%), γ-eudesmol (7.60%), and iso-menthone (7.66%) were the dominant chemical markers. The EO displayed strong antioxidant activity (IC₅₀ = 3.88 ± 0.45 µg/mL) and weak lipase and α-amylase suppressant effects. Notably, the PGEO displayed high α-glucosidase inhibitory efficacy compared with Acarbose, with IC₅₀ doses of 52.44 ± 0.29 and 37.15 ± 0.33 µg/mL, respectively. PGEO remarkably repressed the growth of methicillin-resistant Staphylococcus aureus (MRSA), even more than Ampicillin and Ciprofloxacin, and strongly inhibited Candida albicans compared with Fluconazole. The highest cytotoxic effect of the PGEO was noticed against MCF-7, followed by Hep3B and HeLa cancer cells, with IC₅₀ doses of 32.71 ± 1.25, 40.71 ± 1.89, and 315.19 ± 20.5 µg/mL, respectively, compared with doxorubicin. Moreover, the screened EO demonstrated selective inhibitory activity against COX-1 (IC₅₀ = 14.03 µg/mL). Additionally, PGEO showed a weak suppressant effect on COX-2 (IC₅₀ = 275.97 µg/mL). The current research can be considered the most comprehensive investigation of the chemical and pharmacological characterization of the PGEO. The results obtained in this study demonstrate, without doubt, that this plant represents a rich source of bioactive substances that can be further investigated and authenticated for their medicinal potential.     

Barbeya oleoides Leaves Extracts: In Vitro Carbohydrate Digestive Enzymes Inhibition and Phytochemical Characterization

This study investigated the in vitro inhibitory potential of different solvent extracts of leaves of Barbeya oleoides on key enzymes related to type 2 diabetes mellitus (α-glucosidase and α-amylase) in combination with an aggregation assay (using 0.01% Triton X-100 detergent) to assess the specificity of action. The methanol extract was the most active in inhibiting α-glucosidase and α-amylase, with IC₅₀ values of 6.67 ± 0.30 and 25.62 ± 4.12 µg/mL, respectively. However, these activities were significantly attenuated in the presence of 0.01% Triton X-100. The chemical analysis of the methanol extract was conducted utilizing a dereplication approach combing LC-ESI-MS/MS and database searching. The chemical analysis detected 27 major peaks in the negative ion mode, and 24 phenolic compounds, predominantly tannins and flavonol glycosides derivatives, were tentatively identified. Our data indicate that the enzyme inhibitory activity was probably due to aggregation-based inhibition, perhaps linked to polyphenols.     

Antidiabetic,Antiglycation, and Antioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro

The objective of this work was to investigate the antidiabetic, antiglycation, and antioxidant potentials of ethanolic extract of seeds of Brazilian Passiflora edulis fruits (PESE), a major by-product of the juice industry, and piceatannol (PIC), one of the main phytochemicals of PESE. PESE, PIC, and acarbose (ACB) exhibited IC₅₀ for alpha-amylase, 32.1 ± 2.7, 85.4 ± 0.7, and 0.4 ± 0.1 µg/mL, respectively, and IC₅₀ for alpha-glucosidase, 76.2 ± 1.9, 20.4 ± 7.6, and 252 ± 4.5 µg/mL, respectively. The IC₅₀ of PESE, PIC, and sitagliptin (STG) for dipeptidyl-peptidase-4 (DPP-4) was 71.1 ± 2.6, 1137 ± 120, and 0.005 ± 0.001 µg/mL, respectively. PESE and PIC inhibited the formation of advanced glycation end-products (AGE) with IC₅₀ of 366 ± 1.9 and 360 ± 9.1 µg/mL for the initial stage and 51.5 ± 1.4 and 67.4 ± 4.6 µg/mL for the intermediate stage of glycation, respectively. Additionally, PESE and PIC inhibited the formation of β-amyloid fibrils in vitro up to 100%. IC₅₀ values for 1,1-diphenyl-2-picrylhydrazyl radical (DPPH^•) scavenging activity of PESE and PIC were 20.4 ± 2.1, and 6.3 ± 1.3 µg/mL, respectively. IC₅₀ values for scavenging hypochlorous acid (HOCl) were similar in PESE, PIC, and quercetin (QCT) with values of 1.7 ± 0.3, 1.2 ± 0.5, and 1.9 ± 0.3 µg/mL, respectively. PESE had no cytotoxicity to the human normal bronchial epithelial (BEAS-2B), and alpha mouse liver (AML-12) cells up to 100 and 50 µg/mL, respectively. However, 10 µg/mL of the extract was cytotoxic to non-malignant breast epithelial cells (MCF-10A). PESE and PIC were found to be capable of protecting cultured human cells from the oxidative stress caused by the carcinogen NNKOAc at 100 µM. The in vitro evidence of the inhibition of alpha-amylase, alpha-glucosidase, and DPP-4 enzymes as well as antioxidant and antiglycation activities, warrants further investigation of the antidiabetic potential of P. edulis seeds and PIC.     

UHPLC-DAD Characterization of Origanum vulgare L. from Atacama Desert Andean Region and Antioxidant,Antibacterial and Enzyme Inhibition Activities

The Lamiaceae family is an important source of species among medicinal plants highly valued for their biological properties and numerous uses in folk medicine. Origanum is one of the main genera that belong to this family. The purpose of the study was to determine the phenolic composition of the Origanum vulgare extract and evaluate the antimicrobial, antioxidant, and inhibitory activities of this species that grows in the Andean region of the Atacama Desert. High-performance liquid chromatography was performed to determine the main phenols. Rosmarinic acid was identified as the predominant phenolic compound in this species (76.01 mg/100 g DW), followed by protocatechuic acid, which to our knowledge, no previous study reported similar concentrations in O. vulgare. The oregano extract exhibited a content of total phenolic (3948 mg GAE/100 g DW) and total flavonoid (593 mg QE/100 g DW) with a higher DPPH antioxidant activity (IC₅₀ = 40.58 µg/mL), compared to the same species grown under other conditions. Furthermore, it was found to inhibit α-glucosidase activity with an IC₅₀ value (7.11 mg/mL) lower than acarbose (129.32 mg/mL). Pseudomonas syringae and Pantoea agglomerans (both MIC 0.313 mg/mL and MBC 1.25 mg/mL) were the bacteria most susceptible to oregano extract with the lowest concentration necessary to inhibit bacterial growth. These results open the door for the potential use of this plant to manage chronic diseases, and they expand the knowledge of the species cultivated in arid environmental conditions.