Flavonoids and Phenols,the Potential Anti-Diabetic Compounds from Bauhinia strychnifolia Craib. Stem.

Bioactive compounds from medicinal plants are good alternative treatments for T2DM. They are also sources of lead molecules that could lead to new drug discoveries. In this study, Bauhinia strychnifolia Craib. stem, a traditional Thai medicinal plant for detoxification, was extracted into five fractions, including crude extract, BsH, BsD, BsE, and BsW, by ethanolic maceration and sequential partition with hexane, dichloromethane, ethyl acetate, and water, respectively. Among these fractions, BsE contained the highest amounts of phenolics (620.67 mg GAE/g extract) and flavonoids (131.35 mg QE/g extract). BsE exhibited the maximum inhibitory activity against α-glucosidase (IC₅₀ 1.51 ± 0.01 µg/mL) and DPP-IV (IC₅₀ 2.62 ± 0.03 µg/mL), as well as dominantly promoting glucose uptake on 3T3-L1 adipocytes. Furthermore, the four compounds isolated from the BsE fraction, namely resveratrol, epicatechin, quercetin, and gallic acid, were identified. Quercetin demonstrated the highest inhibitory capacity against α-glucosidase (IC₅₀ 6.26 ± 0.36 µM) and DPP-IV (IC₅₀ 8.25 µM). In addition, quercetin prominently enhanced the glucose uptake stimulation effect on 3T3-L1 adipocytes. Altogether, we concluded that quercetin was probably the principal bioactive compound of the B. strychnifolia stem for anti-diabetic, and the flavonoid-rich fraction may be sufficiently potent to be an alternative treatment for blood sugar control.     

Fatty Acid Analysis,Chemical Constituents,Biological Activity and Pesticide Residues Screening in Jordanian Propolis

Propolis is a resinous natural product collected by honeybees (Apis mellifera and others) from tree exudates that has been widely used in folk medicine. The present study was carried out to investigate the fatty acid composition, chemical constituents, antioxidant, and xanthine oxidase (XO) inhibitory activity of Jordanian propolis, collected from Al-Ghour, Jordan. The hexane extract of Jordanian propolis contained different fatty acids, which are reported for the first time by using GC-FID. The HPLC was carried out to identify important chemical constituents such as fatty acids, polyphenols and α-tocopherol. The antioxidant and xanthine oxidase inhibitory activities were also monitored. The major fatty acid identified were palmitic acid (44.6%), oleic acid (18:1∆⁹cis, 24.6%), arachidic acid (7.4%), stearic acid (5.4%), linoleic acid (18:2∆^9–12cis, 3.1%), caprylic acid (2.9%), lignoceric acid (2.6%), cis-11,14-eicosaldienoic acid (20:2∆^11–14cis, 2.4%), palmitoleic acid (1.5%), cis-11-eicosenoic acid (1.2%), α–linolenic acid (18:3∆^9–12–15cis, 1.1%), cis-13,16-docosadienoic acid (22:2∆^13–16cis, 1.0%), along with other fatty acids. The major chemical constituents identified using gradient HPLC-PDA analysis were pinocembrin (2.82%), chrysin (1.83%), luteolin-7-O-glucoside (1.23%), caffeic acid (1.12%), caffeic acid phenethyl ester (CAPE, 0.79%), apigenin (0.54%), galangin (0.46%), and luteolin (0.30%); while the minor constituents were hesperidin, quercetin, rutin, and vanillic acid. The percentage of α-tocopherol was 2.01 µg/g of the lipid fraction of propolis. Antioxidant properties of the extracts were determined via DPPH radical scavenging. The DPPH radical scavenging activities (IC₅₀) of different extracts ranged from 6.13 to 60.5 µg/mL compared to ascorbic acid (1.21 µg/mL). The xanthine oxidase inhibition (IC₅₀) ranged from 75.11 to 250.74 µg/mL compared to allopurinol (0.38 µg/mL). The results indicate that the various flavonoids, phenolic compounds, α-tocopherol, and other constituents which are present in propolis are responsible for the antioxidant and xanthine oxidation inhibition activity. To evaluate the safety studies of propolis, the pesticide residues were also monitored by LC-MS-MS 4500 Q-Trap. Trace amounts of pesticide residue (ng/mL) were detected in the samples, which are far below the permissible limit as per international guidelines.     

Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC₅₀ values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC₅₀ values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.     

In Vitro Alpha-Glucosidase Inhibitory Activity and the Isolation of Luteolin from the Flower of Gymnanthemum amygdalinum (Delile) Sch. Bip ex Walp.

Diabetes mellitus is a major health issue that has posed a significant challenge over the years. Gymnanthemum amygdalinum is a well-known plant that can be potentially used to treat this disease. Therefore, this study aimed to evaluate the inhibitory effect of its root, stem bark, leaves, and flower extracts on alpha-glucosidase using an in vitro inhibition assay to isolate the bioactive compounds and determine their levels in the samples. The air-dried plant parts were extracted by maceration using methanol. The results showed that the flower extract had the greatest inhibitory effect (IC50 47.29 ± 1.12 µg/mL), followed by the leaves, roots, and stem bark. The methanolic flower extract was further fractionated with different solvents, and the ethyl acetate fraction showed the strongest activity (IC50 19.24 ± 0.12 µg/mL). Meanwhile, acarbose was used as a positive control (IC50 73.36 ± 3.05 µg/mL). Characterization based on UV, 1H-, and 13C-NMR established that the ethyl acetate fraction yielded two flavonoid compounds, namely, luteolin and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxy-4H-chromen-4-on, which had IC50 values of 6.53 ± 0.16 µg/mL and 39.95 ± 1.59 µg/mL, respectively. The luteolin levels in the crude drug, methanolic extract, and ethyl acetate fraction were 3.4 ± 0.2 mg (0.3%), 32.4 ± 0.8 mg (3.2%), and 68.9 ± 3.4 mg (6.9%) per 1 g samples, respectively. These results indicated that the G. amygdalinum flower extract exerted potent inhibitory alpha-glucosidase activity.     

Polycyclic Phenol Derivatives from the Leaves of Spermacoce latifolia and Their Antibacterial and α-Glucosidase Inhibitory Activity

Three new polycyclic phenol derivatives, 2-acetyl-4-hydroxy-6H-furo [2,3-g]chromen-6-one (1), 2-(1′,2′-dihydroxypropan-2′-yl)-4-hydroxy-6H-furo [2,3-g][1]benzopyran-6-one (2) and 3,8,10-trihydroxy-4,9-dimethoxy-6H-benzo[c]chromen-6-one (8), along with seven known ones (3–7, 9 and 10) were isolated for the first time from the leaves of Spermacoce latifolia. Their structures were determined by spectroscopic analysis and comparison with literature-reported data. These compounds were tested for their in vitro antibacterial activity against four Gram-(+) bacteria: Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC), Bacillus subtilis (BS), and the Gram-(−) bacterium Escherichia coli. Compounds 1, 2, 5 and 8 showed antibacterial activity toward SA, BC and BS with MIC values ranging from 7.8 to 62.5 µg/mL, but they were inactive to MRSA. Compound 4 not only showed the best antibacterial activity against SA, BC and BS, but it further displayed significant antibacterial activity against MRSA (MIC 1.95 µg/mL) even stronger than vancomycin (MIC 3.9 µg/mL). No compounds showed inhibitory activity toward E. coli. Further bioassay indicated that compounds 1, 4, 5, 6, 8 and 9 showed in vitro α-glucosidase inhibitory activity, among which compound 9 displayed the best α-glucosidase inhibitory activity with IC₅₀ value (0.026 mM) about 15-fold stronger than the reference compound acarbose (IC₅₀ 0.408 mM). These results suggested that compounds 4, 8 and 9 were potentially highly valuable compounds worthy of consideration to be further developed as an effective anti-MRSA agent or effective α-glucosidase inhibitors, respectively. In addition, the obtained data also supported that S. latifolia was rich in structurally diverse bioactive compounds worthy of further investigation, at least in searching for potential antibiotics and α-glucosidase inhibitors.     

Biological Activities of Lichen-Derived Monoaromatic Compounds

Lichen-derived monoaromatic compounds are bioactive compounds, associated with various pharmacological properties: antioxidant, antifungal, antiviral, cytotoxicity, and enzyme inhibition. However, little is known about data regarding alpha-glucosidase inhibition and antimicrobial activity. Very few compounds were reported to have these activities. In this paper, a series of monoaromatic compounds from a lichen source were isolated and structurally elucidated. They are 3,5-dihydroxybenzoic acid (1), 3,5-dihydroxybenzoate methyl (2), 3,5-dihydroxy-4-methylbenzoic acid (3), 3,5-dihydroxy-4-methoxylbenzoic acid (4), 3-hydroxyorcinol (5), atranol (6), and methyl hematommate (7). To obtain more derivatives, available compounds from the previous reports such as methyl β-orsellinate (8), methyl orsellinate (9), and D-montagnetol (10) were selected for bromination. Electrophilic bromination was applied to 8–10 using NaBr/H₂O₂ reagents to yield products methyl 5-bromo-β-orsellinate (8a), methyl 3,5-dibromo-orsellinate (9a), 3-bromo-D-montagnetol (10a), and 3,5-dibromo-D-montagnetol (10b). Compounds were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 4 showed stronger alpha-glucosidase inhibition than others with an IC₅₀ value of 24.0 µg/mL. Synthetic compound 9a exhibited remarkable activity against Staphylococcus aureus with a MIC value of 4 µg/mL. Molecular docking studies were performed to confirm the consistency between in vitro and in silico studies.     

Chemical Profile,Antimicrobial and Antioxidant Activity Assessment of the Crude Extract and Its Main Flavonoids from Tartary Buckwheat Sprouts

The purpose of this study was to investigate the major flavonoids content and bioactivities of Tartary buckwheat sprouts. The crude methanol extract (ME) of Tartary buckwheat sprouts was abundant in flavonoids, and six major flavonoids, including isoorientin, vitexin, isovitexin, rutin, quercetin, and kaemferol were successfully determined from the sprouts by the high-performance liquid chromatography (HPLC) method. Generally, the flavonoid content of buckwheat sprouts was in the order of rutin > quercetin > isovitexin > vitexin> isoorientin > kaemferol. The highest rutin content of the ME and sprout cultures was 89.81 mg/g and 31.50 mg/g, respectively. Antibacterial activity results indicated the ME displayed notable inhibitory activity against the five tested bacteria, and its minimum inhibitory concentration (MIC) values ranged from 0.8 mg/mL to 3.2 mg/mL. Among the six flavonoids, quercetin was the most active compound, which exhibited strong activity against all tested bacteria except for E. coli and S. epidermidis, with its MIC values ranging from 0.2 mg/mL to 0.4 mg/mL. For the antifungal activity assay, the ME of Tartary buckwheat sprouts and four flavonoids could significantly inhibit the spore germination of two pathogenic fungi, and their inhibitory efficiency was concentration dependent. Quercetin was the most active one, which significantly inhibited the spore germination of F. oxysporum f. sp. vasinfectum and F. oxysporum f. sp. cucumerinum, and its median effective inhibitory concentration (IC₅₀) value was 42.36 and 32.85 µg/mL, respectively. The antioxidant activity results showed that quercetin, kaemferol, and rutin displayed excellent antioxidant activity in the DPPH radical scavenging test, and their IC₅₀ value was calculated as 5.60, 16.23, and 27.95 µg/mL, respectively. This is the first report on the antimicrobial activity of the crude extract of Tartary buckwheat sprouts. These results indicated that the methanol extract of Tartary buckwheat sprouts could be used as a potential antimicrobial or antioxidant agent in the future.     

Biomedical Applications of Scutellaria edelbergii Rech. f.: In Vitro and In Vivo Approach

In the current study, in vitro antimicrobial and antioxidant activities and in vivo anti-inflammatory and analgesic activities of Scutellaria edelbergii Rech. f. (crude extract and subfractions, i.e., n-hexane, ethyl acetate (EtOAc), chloroform, n-butanol (n-BuOH) and aqueous) were explored. Initially, extraction and fractionation of the selected medicinal plant were carried out, followed by phytochemical qualitative tests, which were mostly positive for all the extracts. EtOAc fraction possessed a significant amount of phenolic (79.2 ± 0.30 mg GAE/g) and flavonoid (84.0 ± 0.39 mg QE/g) content. The EtOAc fraction of S. edelbergii exhibited appreciable antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumoniae) strains and significant zones of inhibition were observed against Gram-positive bacterial strains (Bacillus subtilis and Staphylococcus aureus). However, it was found inactive against Candida Albicans and Fusarium oxysporum fungal strains. The chloroform fraction was the most effective with an IC₅₀ value of 172 and 74 µg/mL against DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays, in comparison with standard ascorbic acid 59 and 63 µg/mL, respectively. Moreover, the EtOAc fraction displayed significant in vivo anti-inflammatory activity (54%) using carrageenan-induced assay and significant (55%) in vivo analgesic activity using acetic acid-induced writing assay. In addition, nine known compounds, ursolic acid (UA), ovaul (OV), oleanolic acid (OA), β-sitosterol (BS), micromeric acid (MA), taraxasterol acetate (TA), 5,3′,4′-trihydroxy-7-methoxy flavone (FL-1), 5,7,4′-trihydroxy-6,3′-dimiethoxyflavone (FL-2) and 7-methoxy catechin (FL-3), were isolated from methanolic extract of S. edelbergii. These constituents have never been obtained from this source. The structures of all the isolated constituents were elucidated by spectroscopic means. In conclusion, the EtOAc fraction and all other fractions of S. edelbergii, in general, displayed a significant role as antibacterial, free radical scavenger, anti-inflammatory and analgesic agents which may be due to the presence of these constituents and other flavonoids.     

Three New Isoprenylated Flavones from Artocarpus chama Stem and Their Bioactivities

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3′-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2′,5′-tetrahydroxy-4′-methoxyflavone (3), and five known compounds, namely homoeriodictyol (4), isocycloartobilo-xanthone (5), artocarpanone (6), naringenin (7), and artocarpin (8). From the screening result, A. chama extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC₅₀ of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds 3, 4, 5, 6, and 8 showed strong activity against Staphylococcus epidermidis, S. aureus, methicillin-resistant S. aureus, and Cutibacterium acnes. This study is the first report on phytochemical investigation with new compounds and biological activities of A. chama. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms.     

Alpha-Glucosidase Inhibition and Molecular Docking of Isolated Compounds from Traditional Thai Medicinal Plant,Neuropeltis racemosa Wall.

Neuropeltis racemosa Wall. (Convolvulaceae) is wildly distributed in Asia. Its stem is used as the component in traditional Thai recipes for treatments of muscle rigidity, skin disorder, dysentery, and hypoglycemia. However, the chemical constituents and biological activities of N. racemosa have not been reported. From a screening assay, N. racemosa stem crude extract showed the potent effect on alpha-glucosidase inhibition at 2 mg/mL as 96.09%. The bioassay-guiding isolation led to 5 compounds that were identified by spectroscopic techniques as scopoletin (1), syringic acid (2), methyl 3-methyl-2-butenoate (3), N-trans-feruloyltyramine (4), and N-trans- coumaroyltyramine (5). Compounds 1, 4, and 5 exhibited an IC₅₀ of 110.97, 29.87, and 0.92 µg/mL, respectively, while the IC₅₀ of positive standard, acarbose was 272.72 µg/mL. Kinetic study showed that compound 1 performed as the mixed-type inhibition mechanism, whereas compounds 4 and 5 displayed the uncompetitive inhibition mechanism. The docking study provided the molecular understanding of isolated aromatic compounds (1, 2, 4 and 5) to alpha-glucosidase. Hence, this study would be the first report of isolated compounds and their anti-alpha-glucosidase activity with the mechanism of action from N. racemosa. Thus, these active compounds will be further studied to be the lead compounds among natural antidiabetic drugs.     

Anticancer,Anticoagulant, Antioxidant and Antimicrobial Activities of Thevetia peruviana Latex with Molecular Docking of Antimicrobial and Anticancer Activities

Natural origin molecules represent reliable and excellent sources to overcome some medicinal problems. The study of anticancer, anticoagulant, and antimicrobial activities of Thevetia peruviana latex were the aim of the current research. An investigation using high-performance liquid chromatography (HPLC) revealed that the major content of the flavonoids are rutin (11.45 µg/mL), quersestin (7.15 µg/mL), naringin (5.25 µg/mL), and hisperdin (6.07 µg/mL), while phenolic had chlorogenic (12.39 µg/mL), syringenic (7.45 µg/mL), and ferulic (5.07 µg/mL) acids in latex of T. peruviana. Via 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging, the experiment demonstrated that latex had a potent antioxidant activity with the IC₅₀ 43.9 µg/mL for scavenging DPPH. Hemolysis inhibition was 58.5% at 1000 µg/mL of latex compared with 91.0% at 200 µg/mL of indomethacin as positive control. Negligible anticoagulant properties of latex were reported where the recorded time was 11.9 s of prothrombin time (PT) and 29.2 s of the activated partial thromboplastin time (APTT) at 25 µg/mL, compared with the same concentration of heparin (PT 94.6 s and APPT 117.7 s). The anticancer potential of latex was recorded against PC-3 (97.11% toxicity) and MCF-7 (96.23% toxicity) at 1000 μg/mL with IC₅₀ 48.26 μg/mL and 40.31 µg/mL, respectively. Disc diffusion assessment for antimicrobial activity recorded that the most sensitive tested microorganisms to latex were Bacillus subtilis followed by Escherichia coli, with an inhibition zone (IZ) of 31 mm with minimum inhibitory concentration (MIC) (10.2 μg/mL) and 30 mm (MIC, 12.51 μg/mL), respectively. Moreover, Candida albicans was sensitive (IZ, 28 mm) to latex, unlike black fungus (Mucor circinelloides). TEM examination exhibited ultrastructure changes in cell walls and cell membranes of Staphylococcus aureus and Pseudomonas aeruginosa treated with latex. Energy scores of the molecular docking of chlorogenic acid with E. coli DNA (7C7N), and Rutin with human prostate-specific antigen (3QUM) and breast cancer-associated protein (1JNX), result in excellent harmony with the experimental results. The outcome of research recommended that the latex is rich in constituents and considered a promising source that contributes to fighting cancer and pathogenic microorganisms.     

Determination of Flavonoids in Selected Scleranthus Species and Their Anti-Collagenase and Antioxidant Potential

A new 5,7-dihydroxy-3′-methoxy-4′-acetoxyflavone-8-C-β-d-arabinopyranoside-2″-O-(4‴-acetoxy)-glucoside (6) and three known flavone C-glycosides—5,7,3′,4′-tetrahydroxyflavone-6-C-xyloside-8-C-β-d-glucoside (lucenin-1) (7), 5,7,3′-trihydroxyflavone-6-C-glucoside-8-C-β-d-glucoside (vicenin-2) (8), and 5,7,4′-trihydroxy-3′-methoxyflavone-6-C-β-d-glucopyranoside-8-C-α-arabinopyranoside (chrysoeriol-6-C-β-d-glucopyranoside-8-C-α-arabinopyranoside) (9)—were isolated from aerial parts of Scleranthus perennis L. (Caryophyllaceae). Their structures were determined through the use of comprehensive spectroscopic and spectrometric methods, and a method for the quantification of the major constituents of S. perennis and S. annuus L. was developed. Furthermore, the anti-collagenase and antioxidant activities of all isolated compounds obtained from extracts and fractions from both Scleranthus species were evaluated. The highest percentage of collagenase inhibition (at 400 µg/mL) was distinguished for methanolic extracts (22.06%, 32.04%) and ethyl acetate fractions (16.59%, 14.40%) from S. annuus and S. perennis. Compounds 6–9 displayed moderate inhibitory activity, with IC₅₀ values ranging from 39.59–73.86 µM.     

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.     

Chemical Evaluation,Antioxidant, Antiproliferative,Anti-Inflammatory and Antibacterial Activities of Organic Extract and Semi-Purified Fractions of the Adriatic Sea Fan,Eunicella cavolini

Due to sedentary lifestyle and harsh environmental conditions, gorgonian coral extracts are recognized as a rich source of novel compounds with various biological activities, of interest to the pharmaceutical and cosmetic industries. The presented study aimed to perform chemical screening of organic extracts and semi-purified fractions obtained from the common Adriatic gorgonian, sea fan, Eunicella cavolini (Koch, 1887) and explore its abilities to exert different biological effects in vitro. Qualitative chemical evaluation revealed the presence of several classes of secondary metabolites extended with mass spectrometry analysis and tentative dereplication by using Global Natural Product Social Molecular Networking online platform (GNPS). Furthermore, fractions F4 and F3 showed the highest phenolic (3.28 ± 0.04 mg GAE/g sample) and carotene (23.11 ± 2.48 mg β-CA/g sample) content, respectively. The fraction F3 inhibited 50% of DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) and ABTS (2,2′-azino-bis (3-ethylbenzthiazolin-6-yl) sulfonic acid) radicals at the concentrations of 767.09 ± 11.57 and 157.16 ± 10.83 µg/mL, respectively. The highest anti-inflammatory potential was exhibited by F2 (IC₅₀ = 198.70 ± 28.77 µg/mL) regarding the inhibition of albumin denaturation and F1 (IC₅₀ = 254.49 ± 49.17 µg/mL) in terms of soybean lipoxygenase inhibition. In addition, the most pronounced antiproliferative effects were observed for all samples (IC₅₀ ranging from 0.82 ± 0.14–231.18 ± 46.13 µg/mL) against several carcinoma cell lines, but also towards non-transformed human fibroblasts pointing to a generally cytotoxic effect. In addition, the antibacterial activity was tested by broth microdilution assay against three human pathogenic bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The latter was the most affected by fractions F2 and F3. Finally, further purification, isolation and characterization of pure compounds from the most active fractions are under investigation.     

Chemical and Pharmacological Potential of Coccoloba cowellii,an Endemic Endangered Plant from Cuba

Coccoloba cowellii Britton (Polygonaceae) is an endemic and critically endangered plant that only grows in Camagüey, a province of Cuba. In this study, a total of 13 compounds were identified in a methanolic leaf extract, employing a dereplication of the UHPLC-HRMS data by means of feature-based molecular networking (FBMN) analysis in the Global Natural Products Social Molecular Network (GNPS), together with the interpretation of the MS/MS data and comparison with the literature. The major constituents were glucuronides and glycosides of myricetin and quercetin, as well as epichatechin-3-O-gallate, catechin, epicatechin and gallic acid, all of them being reported for the first time in C. cowellii leaves. The leaf extract was also tested against various microorganisms, and it showed a strong antifungal effect against Candida albicans ATCC {"type":"entrez-nucleotide","attrs":{"text":"B59630","term_id":"2614348"}}B59630 (azole-resistant) (IC₅₀ 2.1 µg/mL) and Cryptococcus neoformans ATCC {"type":"entrez-nucleotide","attrs":{"text":"B66663","term_id":"2640641"}}B66663 (IC₅₀ 4.1 µg/mL) with no cytotoxicity (CC₅₀ > 64.0 µg/mL) on MRC-5 SV2 cells, determined by the resazurin assay. Additionally, the extract strongly inhibited COX-1 and COX-2 enzyme activity using a cell-free experiment in a dose-dependent manner, being significantly more active on COX-1 (IC₅₀ 4.9 µg/mL) than on COX-2 (IC₅₀ 10.4 µg/mL). The constituents identified as well as the pharmacological activities measured highlight the potential of C. cowellii leaves, increasing the interest in the implementation of conservation strategies for this species.     

Phenolics Profiling of Carpobrotus edulis (L.) N.E.Br. and Insights into Molecular Dynamics of Their Significance in Type 2 Diabetes Therapy and Its Retinopathy Complication

Adverse effects associated with synthetic drugs in diabetes therapy has prompted the search for novel natural lead compounds with little or no side effects. Effects of phenolic compounds from Carpobrotus edulis on carbohydrate-metabolizing enzymes through in vitro and in silico methods were assessed. Based on the half-maximal inhibitory concentrations (IC₅₀), the phenolic extract of the plant had significant (p < 0.05) in vitro inhibitory effect on the specific activity of alpha-amylase (0.51 mg/mL), alpha-glucosidase (0.062 mg/mL) and aldose reductase (0.75 mg/mL), compared with the reference standards (0.55, 0.72 and 7.05 mg/mL, respectively). Molecular interactions established between the 11 phenolic compounds identifiable from the HPLC chromatogram of the extract and active site residues of the enzymes revealed higher binding affinity and more structural compactness with procyanidin (−69.834 ± 6.574 kcal/mol) and 1,3-dicaffeoxyl quinic acid (−42.630 ± 4.076 kcal/mol) as potential inhibitors of alpha-amylase and alpha-glucosidase, respectively, while isorhamnetin-3-O-rutinoside (−45.398 ± 4.568 kcal/mol) and luteolin-7-O-beta-d-glucoside (−45.102 ± 4.024 kcal/mol) for aldose reductase relative to respective reference standards. Put together, the findings are suggestive of the compounds as potential constituents of C. edulis phenolic extract responsible for the significant hypoglycemic effect in vitro; hence, they could be exploited in the development of novel therapeutic agents for type-2 diabetes and its retinopathy complication.     

Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Hypericum afrum Lam.: Phytochemistry,In Vitro Testing and Modeling Studies

The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC₅₀ values of 12.35, 13.53 and 12.93 µg/mL and with IC₉₀ values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-β-d-galactopyranoside (6) and myricetin-3’-O-β-d-glucopyranoside (7). Myricetin-3’-O-β-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI–MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC₅₀ and IC₉₀ values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.     

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.     

The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure–activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e–f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl₂ or 5f with 3,4-Cl₂). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC₅₀ = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160–4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-β-d-glucosaminide and 4-nitrophenyl-β-d-N,N′,N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing β-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.     

Chemical composition,antimicrobial, and lipase enzyme activity of essential oil and solvent extracts from Serapias orientalis subsp. orientalis

The volatile components of essential oil (EO), SPME, and SPME of solvent extracts ( n -hexane, methanol, and water) obtained from fresh Serapias orientalis subsp. orientalis ( Soo ) were analyzed by GC-FID/MS. EO of Soo gave 11 compounds in the percentage of 99.97%; capronaldehyde (37.01%), 2-( E )-hexenal (23.19%), and n -nonanal (19.05%) were found to be major constituents. SPME GC-FID/MS analyses of fresh plant and solvent extracts of Soo revealed 7, 12, 7, and 4 compounds within the range of 99.7% to 99.9%. Limonene (76.5%, 41.7%, and 61.3%) was the major compound in SPMEs of the n -hexane and methanol extracts. α -Methoxy- p -cresol (52.9%) was the main component in its water extract. The antimicrobial activity of EO and the solvent extracts of Soo were screened against 9microorganisms. EO showed the best activity against Mycobacterium smegmatis , with 79.5 µg/mL MIC value. The n -hexane, methanol, and water extracts were the most active against the Staphylococcus aureus within the range of 81.25–125.0 µg/mL (MIC). IC ₅₀ values for the lipase enzyme inhibitory activity of EO and solvent extracts ( n -hexane, methanol, and water) were determined to be 59.87 µg/mL, 64.03 µg/mL, 101.91 µg/mL, and 121.24 µg/mL, respectively.