In Vitro and Molecular Docking Evaluation of the Anticholinesterase and Antidiabetic Effects of Compounds from Terminalia macroptera Guill. & Perr. (Combretaceae).

Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From 1H and 13C NMR data, the compounds were identified as 3,3'-di-O-methyl ellagic acid (1), 3,3',4'-tri-O-methyl ellagic acid-4-O-ß-D-xylopyranoside (2), 3,3',4'-tri-O-methyl ellagic acid-4-O-ß-D-glucopyranoside (3), 3,3'-di-O-methyl ellagic acid-4-O-ß-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1-4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3'-di-O-methyl ellagic acid, with IC50 values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds (1-5). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for 1-11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of -4.03 to -10.20 kcalmol-1. Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.

Comparative assessment of phenolic composition profile and biological activities of green extract and conventional extracts of Salvia sclarea.

In recent years, there have been an attempt to develop safe and environmental friendly solvents to replace conventional solvents, and use for extraction bioactive compounds from natural sources. A current investigation involved the preparation of green, methanolic, and ultrasonic extracts of S. sclarea, and compared their phenolic profiling using HPLC-DAD, antibacterial, antioxidant, and enzyme inhibition activities. The HPLC-DAD analysis revealed that Rosmarinic acid was the main content in all extracts, with Ellagic acid only present in the green extract. The green extract exhibited superior anti-biofilm activity against S. Aureus and E. Faecalis compared to the other extracts at MIC concentration. Furthermore, the green extract also displayed the highest inhibition of swarming motility in P. Aeruginosa with inhibition range 68.0 ± 2.1 (MIC) to 19.5 ± 0.6 (MIC/4). and better enzyme inhibitory activity against BChE (with IC50 = 131.6 ± 0.98 µg/mL) and AChE (with inhibition 47.00 ± 1.50%) compared to the other extracts; while, the ultrasonic extract showed strong inhibition of violacein production by C. Violaceum with a inhibition range 05.5 ± 0.1 (MIC/32) to 100 ± 0.00 (MIC), followed by the green extract with a inhibition range 15.0 ± 0.5 (MIC/8) to 100 ± 0.00 (MIC), additionally, the ultrasonic and methanoic extracts showed significant activity against urease enzyme with (IC50 = 171.6 ± 0.95 µg/mL and IC5 0 = 187.5 ± 1.32 µg/mL) respectively. Both the green and methanolic extracts showed considerable antioxidant activities, as ß-carotene-linoleic acid (IC50 = 5.61 ± 0.47 µg/mL and 5.37 ± 0.27 µg/mL), DPPH· (IC50 = 19.20 ± 0.70 µg/mL and 16.31 ± 0.23 µg/mL), ABTS·+(IC50 = 8.64 ± 0.63 µg/mL and 6.50 ± 0.45 µg/mL) and CUPRAC (A0.5 = 17.22 ± 0.36 µg/mL and 12.28 ± 0.12 µg/mL) respectively, likewise the green extract performing better in metal chelating compared to the other extracts. The green extraction is reported as a cost effective and solvent free method for extracting natural products that produces compounds free of toxic chemicals. This could be the method to be used in the industries as a renewable method.

Inhibition of biofilm, quorum-sensing, and swarming motility in pathogenic bacteria by magnetite, manganese ferrite, and nickel ferrite nanoparticles.

Resistance to antibiotics by pathogenic bacteria constitutes a health burden and nanoparticles (NPs) are being developed as alternative and multipurpose antimicrobial substances. Magnetite (Fe3O4 np), manganese ferrite (MnFe2O4 np) and nickel ferrite (NiFe3O4 np) NPs were synthesized and characterized using thermogravimetric analysis, transmission electron microscopy, Fourier transformed infra-red, and X-ray diffraction. The minimal inhibitory concentrations (MIC) ranged from 0.625 to 10 mg/mL against gram-positive (Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212), gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and candida (Candida albicans ATCC 10239 and Candida tropicalis ATCC 13803) species. The NPs exhibited violacein inhibition against Chromobacterium violaceum CV12472 of 100% at MIC and reduced to 27.2% ± 0.8% for magnetite NPs, 12.7% ± 0.3% for manganese ferrite NPs and 43.1% ± 0.2% for nickel ferrite NPs at MIC/4. Quorum-sensing (QS) inhibition zones against C. violaceum CV026 were 12.5 ±0.6 mm for Fe3O4 np, 09.1 ± 0.5 mm for MnFe3O4 NP and 17.0 ± 1.2 mm for NiFe3O4 np. The NPs inhibited swarming motility against P. aeruginosa PA01 and biofilm against six pathogens and the gram-positive biofilms were more susceptible than the gram-negative ones. The NiFe2O4 np had highest antibiofilm activity against gram-positive and gram-negative bacteria as well as highest QS inhibition while Fe3O4 NP had highest biofilm inhibition against candida species. The synthesized magnetic NPs can be used in developing anti-virulence drugs which reduce pathogenicity of bacteria as well as resistance.

Assessment of Chemical Composition and In Vitro Antioxidant, Antidiabetic, Anticholinesterase and Microbial Virulence-Quenching Effects of Salad Burnet (Sanguisorba minor L.) Harvested from Algeria.

Sanguisorba minor is a medicinal vegetable used in seasoning desserts, juices, and beverages. An evaluation of the total flavonoid, phenolic, tannin and anthocyanin contents indicated that these classes of compounds are distributed variably in the different fractions. In summary, the HPLC-DAD analyses enabled the identification and quantification of thirteen phenolic compounds in an ethyl acetate extract (EAE), nine in a dichloromethane extract (DCME), seven in an aqueous extract (AQE) and four in a butanol extract (BE). Rutin was the most abundant phenolic compound in the BE (278.4 ± 1.20 µg/g) and AQE (32.87 ± 0.23 µg/g) fractions, while apigenin was the most abundant in the DCME (84.75 ± 0.60 µg/g) and EAE (156.8 ± 0.95 µg/g) fractions. The presence of phenolic compounds in the fractions conferred good antioxidant capacity, especially the EAE and DCME fractions, which both exhibited higher antioxidant effects than BHA and α-tocopherol in DPPH• and CUPRAC assays. Additionally, in the ABTS•+ assay, EAE (IC50 = 9.27 ± 0.33 µg/mL) was more active than α-tocopherol (IC50 = 35.50 ± 0.55 µg/mL), and BHA (IC50 = 12.70 ± 0.10 µg/mL). At 200 µg/mL, the fractions inhibited acetylcholinesterase and butyrylcholinesterase as well as α-amylase and α-glucosidase, indicating that they can slow neurodegeneration and hyperglycemia. Minimal inhibitory concentration (MIC) values ranged from 0.312 mg/mL to 1.25 mg/mL, and fractions showed good biofilm inhibition against Staphylococcus aureus and Escherichia coli. The extracts exhibited good violacein inhibition in Chromobacterium violaceum CV12472 and Chromobacterium violaceum CV026, despite the supply of external acyl-homoserine lactone to CV026. The antioxidant, quorum-sensing, antibiofilm and enzyme inhibition attributes indicate the potential for the application of S. minor as a food preservative.

Evaluation of anti-quorum sensing and antibiofilm effects of secondary metabolites from Gambeya lacourtiana (De Wild) Aubr. & Pellegr against selected pathogens.

BACKGROUND: Microbial infections cause serious health problems especially with the rising antibiotic resistance which accounts for about 700,000 human deaths annually. Antibiotics which target bacterial death encounter microbial resistance with time, hence, there is an urgent need for the search of antimicrobial substances which target disruption of virulence factors such as biofilm and quorum sensing (QS) with selective pressure on the pathogens so as to avoid resistance. METHODS: Natural products are suitable leads for antimicrobial drugs that can inhibit bacterial biofilms and QS. Twenty compounds isolated from the medicinal plant Gambeya lacourtiana were evaluated for their antibiofilm and anti-quorum sensing effects against selected pathogenic bacteria. RESULTS: Most of the compounds inhibited violacein production in Chromobacterium violaceum CV12472 and the most active compound, Epicatechin had 100% inhibition at MIC (Minimal Inhibitory Concentration) and was the only compound to inhibit violacein production at MIC/8 with percentage inhibition of 17.2 ± 0.9%. Since the bacteria C. violaceum produces violacein while growing, the inhibition of the production of this pigment reflects the inhibition of signal production. Equally, some compounds inhibited violacein production by C. violaceum CV026 in the midst of an externally supplied acylhomoserine lactone, indicating that they disrupted signal molecule reception. Most of the compounds exhibited biofilm inhibition on Staphyloccocus aureus, Escherichia coli and Candida albicans and it was observed that the Gram-positive bacteria biofilm was most susceptible. The triterpenoids bearing carboxylic acid group, the ceramide and epicatechin were the most active compounds compared to others. CONCLUSION: Since some of the compounds disrupted QS mediated processes in bacteria, it indicates that this plant is a source of antibiotics drugs that can reduce microbial resistance.

In Vitro and In Silico Evaluation of Anticholinesterase and Antidiabetic Effects of Furanolabdanes and Other Constituents from Graptophyllum pictum (Linn.) Griffith.

Graptophyllum pictum is a tropical plant noticeable for its variegated leaves and exploited for various medicinal purposes. In this study, seven compounds, including three furanolabdane diterpenoids, i.e., Hypopurin E, Hypopurin A and Hypopurin B, as well as with Lupeol, ß-sitosterol 3-O-ß-d-glucopyranoside, stigmasterol 3-O-ß-d-glucopyranoside and a mixture of ß-sitosterol and stigmasterol, were isolated from G. pictum, and their structures were deduced from ESI-TOF-MS, HR-ESI-TOF-MS, 1D and 2D NMR experiments. The compounds were evaluated for their anticholinesterase activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BchE), as well as their antidiabetic potential through inhibition of α-glucosidase and α-amylase. For AChE inhibition, no sample had IC50 within tested concentrations, though the most potent was Hypopurin A, which had a percentage inhibition of 40.18 ± 0.75%, compared to 85.91 ± 0.58% for galantamine, at 100 µg/mL. BChE was more susceptible to the leaves extract (IC50 = 58.21 ± 0.65 µg/mL), stem extract (IC50 = 67.05 ± 0.82 µg/mL), Hypopurin A (IC50 = 58.00 ± 0.90 µg/mL), Hypopurin B (IC50 = 67.05 ± 0.92 µg/mL) and Hypopurin E (IC50 = 86.90 ± 0.76 µg/mL). In the antidiabetic assay, the furanolabdane diterpenoids, lupeol and the extracts had moderate to good activities. Against α-glucosidase, lupeol, Hypopurin E, Hypopurin A and Hypopurin B had appreciable activities but the leaves (IC50 = 48.90 ± 0.17 µg/mL) and stem (IC50 = 45.61 ± 0.56 µg/mL) extracts were more active than the pure compounds. In the α-amylase assay, stem extract (IC50 = 64.47 ± 0.78 µg/mL), Hypopurin A (IC50 = 60.68 ± 0.55 µg/mL) and Hypopurin B (IC50 = 69.51 ± 1.30 µg/mL) had moderate activities compared to the standard acarbose (IC50 = 32.25 ± 0.36 µg/mL). Molecular docking was performed to determine the binding modes and free binding energies of Hypopurin E, Hypopurin A and Hypopurin B in relation to the enzymes and decipher the structure-activity relationship. The results indicated that G. pictum and its compounds could, in general, be used in the development of therapies for Alzheimer's disease and diabetes.

Disruption of Biofilm Formation and Quorum Sensing in Pathogenic Bacteria by Compounds from Zanthoxylum Gilletti (De Wild) P.G. Waterman.

Microbial resistance is facilitated by biofilm formation and quorum-sensing mediated processes. In this work, the stem bark (ZM) and fruit extracts (ZMFT) of Zanthoxylum gilletii were subjected to column chromatography and afforded lupeol (1), 2,3-epoxy-6,7-methylenedioxyconiferyl alcohol (3), nitidine chloride (4), nitidine (7), sucrose (6) and sitosterol-ß-D-glucopyranoside (2). The compounds were characterized using MS and NMR spectral data. The samples were evaluated for antimicrobial, antibiofilm and anti-quorum sensing activities. Highest antimicrobial activity was exhibited by compounds 3, 4 and 7 against Staphylococcus aureus (MIC 200 µg/mL), compounds 3 and 4 against Escherichia coli (MIC = 100 µg/mL) and compounds 4 and 7 against Candida albicans (MIC = 50 µg/mL). At MIC and sub-MIC concentrations, all samples inhibited biofilm formation by pathogens and violacein production in C. violaceum CV12472 except compound 6. Good disruption of QS-sensing in C. violaceum revealed by inhibition zone diameters were exhibited by compounds 3 (11.5 ± 0.5 mm), 4 (12.5 ± 1.5 mm), 5 (15.0 ± 0.8 mm), 7 (12.0 ± 1.5 mm) as well as the crude extracts from stem barks (16.5 ± 1.2 mm) and seeds (13.0 ± 1.4 mm). The profound inhibition of quorum sensing mediated processes in test pathogens by compounds 3, 4, 5 and 7 suggests the methylenedioxy- group that these compounds possess as the possible pharmacophore.

In vitro α-glucosidase inhibitory activity of isolated compounds and semisynthetic derivative from aerial parts of Erythrina senegalensis DC.

The current study was conducted to isolate the phytoconstituents from Erythrina senegalensis leaves and stem bark and evaluate their inhibitory activity against α-glucosidase, digestive enzyme related to diabetes mellitus. Phytochemical investigation of the leaves resulted in the isolation of three saponins (3-5), two triterpenoids (7 and 8) and two steroids (10a and 10b) as inseparable mixture, while one saponin (6), one triterpenoid (9) and one mixture of two cinnamates (2a and 2b) were isolated from the stem bark. Except for compounds 2 b, 7, 8, 10a and 10 b all the isolated compounds are reported here for the first time from the genus Erythrina. Acetylation of the mixture of two cinnamates (2a and 2b) led to a new diester derivative (1) trivially called erythrinamate. The extracts and pure compounds (3, 4, 6) showed good α-glucosidase inhibitory activity compared to the standard drug acarbose. The findings suggest that saponins of E. senegalensis could be used to develop potential anti-hyperglycemic drugs.

Chronic Gastric Ulcer Healing Actions of the Aqueous Extracts of Staple Plant Foods of the North-West, Adamawa, and West Regions of Cameroon.

Aim: This study is aimed at establishing phenolic compound profile and assessing the possible antiulcer activities of aqueous extracts of some staple plant foods from the West and North-West regions of Cameroon against chronic gastric ulcer models in rats. Materials and Methods: Phenolic constituents of extracts were evaluated using HPLC-DAD. Aqueous extracts of Corchorus olitorius, Solanum nigrum, Vigna unguiculata, Triumfetta pentandra, "nkui" spices, and "yellow soup" spices were tested at two doses (200 and 400 mg/kg). After treatments, animals were sacrificed, healing percentage and antioxidant status (catalase, superoxide dismutase, and glutathione peroxidase) were evaluated, and histological examination of gastric mucosa was realized. Results: HPLC-DAD revealed that p-hydroxybenzoic and protocatechuic acids were the phenolic compound present in all extracts. Oral administration of extracts (200 and 400 mg/kg) significantly reduced ulcer surface value and significantly increased mucus production compared to the control groups (p < 0.05). Histological study supported the observed healing activity of different extracts characterized by a reduced inflammatory response. Moreover, administration of aqueous extracts increased the activity of antioxidant enzymes. Conclusion: This study revealed that aqueous extracts of Solanum nigrum, Corchorus olitorius, Vigna unguiculata, Triumfetta pentandra, "yellow soup" spices, and "nkui" spices possess healing antiulcer effects against models of gastric ulcers. The antiulcer mechanisms involved may include increase of gastric mucus production and improvement of the antioxidant activity of gastric tissue. These activities may be due to the phenolic compounds identified in the extracts, especially p-hydroxybenzoic and protocatechuic acids present in all extracts and with known antioxidant, cytoprotective, and healing properties. However, all the diets may promote the healing process of chronic ulcers caused by excessive alcohol consumption/stress.

Antibiofilm and Anti-Quorum Sensing Potential of Cycloartane-Type Triterpene Acids from Cameroonian Grassland Propolis: Phenolic Profile and Antioxidant Activity of Crude Extract.

Propolis is very popular for its beneficial health properties, such as antimicrobial activity and antioxidant effects. It is one of the most long-serving traditional medicines to mankind due to its interesting chemical diversity and therapeutic properties. The detailed chemical information of propolis samples is very necessary to guarantee its safety and for it to be accepted into health care systems. The phenolic profile of the hydroethanolic extract was determined using HPLC-DAD, and the antioxidant was evaluated using five complementary methods. Triterpenoids were isolated using column chromatography and characterized using 1H NMR and 13C NMR. The effects of the extract and the isolated compounds on quorum sensing mediated processes and biofilm formation in bacteria were evaluated. Protocatechic acid (40.76 ± 0.82 µg/g), 4-hydroxybenzoic acid (24.04 ± 0.21 µg/g), vanillic acid (29.90 ± 1.05 µg/g), quercetin (43.53 ± 1.10 µg/g), and luteolin (4.44 ± 0.48 µg/g) were identified and quantified. The extract showed good antioxidant activity in the DPPH•, ABTS•+, CUPRAC, and metal chelating assays, and this antioxidant effect was confirmed by cyclic voltammetry. 27-Hydroxymangiferonic acid (1), Ambolic acid (2), and Mangiferonic acid (3) were isolated from anti-quorum sensing activity at MIC, and it was indicated that the most active sample was the extract with inhibition diameter zone of 18.0 ± 1.0 mm, while compounds 1, 2, and 3 had inhibition zones of 12.0 ± 0.5 mm, 9.0 ± 1.0 mm, and 12.3 ± 1.0 mm, respectively. The samples inhibited the P. aeruginosa PA01 swarming motility at the three tested concentrations (50, 75, and 100 µg/mL) in a dose-dependent manner. The propolis extract was able to inhibit biofilm formation by S. aureus, E. coli, P. aeruginosa, C. albicans, and C. tropicalis at MIC concentration. Compound 1 proved biofilm inhibition on S. aureus, L. monocytogenes, E. faecalis, E. coli, and C. tropicalis at MIC and MIC/2; compound 2 inhibited the formation of biofilm at MIC on S. aureus, E. faecalis, E. coli, S. typhi, C. albicans, and C. tropicalis; and compound 3 inhibited biofilm formation on E. faecalis, E. coli, C. albicans, and C. tropicalis and further biofilm inhibition on E. coli at MIC/4 and MIC/8. The studied propolis sample showed important amounts of cycloartane-type triterpene acids, and this indicates that there can be significant intra-regional variation probably due to specific flora within the vicinity. The results indicate that propolis and its compounds can reduce virulence factors of pathogenic bacteria.

Peptide conjugates of 18ß-glycyrrhetinic acid as potent inhibitors of α-glucosidase and AGEs-induced oxidation.

18ß-Glycyrrhetinic acid (18ß-GA) is known for several biological activities, and has been the focus of extensive research for the development of therapeutic agents. In the current study, 18ß-GA-peptide conjugates 2-11 were evaluated for their in vitro α-glucosidase inhibitory and antiglycation activities. Structure-activity relationship (SAR) established and molecular interactions of active bioconjugates with the enzyme's binding sites were predicted through molecular modeling approach. In tripeptide moiety of conjugates 2-11, peptide residue at position 1 was found to have a significant role on α-glucosidase inhibition. The most active 18ß-GA-peptide conjugates 5 (18ß-GA-Cys1-Tyr2-Gly3), and 8 (18ß-GA-Pro1-Tyr2-Gly3) exhibited several-fold potent α-glucosidase inhibition (IC50 values 20-28 µM), as compared to standard drug acarbose (IC50 = 875.8 ± 2.10 µM). Kinetic studies of potent compounds, 4-8 revealed that conjugate 5 exhibits competitive-type of inhibition, while conjugates 6-8 showed a non-competitive type of inhibition. The simulation studies also supported the kinetic results that conjugate 5 (18ß-GA-Cys1-Tyr2-Gly3) inhibits the α-glucosidase enzyme by blocking its substrate binding site. AGEs-induced NO• inhibitors play an important role in controlling the inflammation associated with diabetes mellitus. The peptide conjugates 2-11 were also evaluated in vitro for AGEs-induced NO• inhibition using RAW 264.7 macrophage cell line. Our data revealed that conjugates 7-10 were the more potent AGEs-induced NO• inhibitors, comparable to standards rutin, and PDTC. The peptide conjugate 5 (a competitive inhibitor of α-glucosidase) also exhibited a strong inhibitory activity against AGEs-induced NO• production. Furthermore, peptide conjugates 2-11 were found non-cytotoxic to mouse fibroblast NIH-3T3, and murine macrophages RAW 264.7 cell lines. In conclusion, our data demonstrates that besides possessing strong α-glucosidase inhibition, the newly synthesized peptide conjugates also alleviated the AGEs-induced NO• production in RAW macrophages. Dual inhibition of α-glucosidase enzyme, and AGEs-induced NO• production by 18ß-GA-peptide conjugates qualify them for further research in anti-diabetic drug discovery.

A new abietane-type diterpenoid from roots of Burkea africana Hook (Fabaceae) with α-amylase inhibitory potential.

A new abietane-type diterpenoid, rubesanolidic acid (1), alongside six known compounds including ß-sitosterol (2), lupeol (3), betulinic acid (4) ursolic acid (5), ß-sitosterol 3-O-ß-D-glucopyranoside (6) and stigmasterol 3-O-ß-D-glucopyranoside (7) were isolated from the roots of Burkea africana through column chromatography. Their structures were elucidated from spectroscopic analyses (UV, IR, MS, 1D and 2D NMR) data and by comparison with data from previous studies. The extract and compounds were tested for their α-amylase inhibition. The extract was more active than the isolated compounds with a percentage inhibition of 51.0 ± 2.5% at 400 µg/mL and was the only sample showing above 50% inhibition at this dose. Amongst the isolated compounds and at the dose of 400 µg/mL, the new diterpenoid Rubesanolidic acid exibited the highest percentage inhibition of α-amylase of 38.2 ± 2.0% while ß-sitosterol showed the lowest inhibition of 9.6 ± 0.5%. The results indicate that B. africana is a potential source of antidiabetic compounds.

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-ß-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.

Chemical Composition, Anti-Quorum Sensing, Enzyme Inhibitory, and Antioxidant Properties of Phenolic Extracts of Clinopodium nepeta L. Kuntze.

Phenolic extracts of Clinopodium nepeta were prepared and their preliminary phenolic profiles determined using HPLC-DAD with 26 phenolic standards. Apigenin (21.75 ± 0.41 µg/g), myricetin (72.58 ± 0.57 µg/g), and rosmarinic acid (88.51 ± 0.55 µg/g) were the most abundant compounds in DCM (dichloromethane), AcOEt (ethyl acetate), and BuOH (butanol) extracts, respectively. The DCM and AcOEt extracts inhibited quorum-sensing mediated violacein production by C. violaceum CV12472. Anti-quorum-sensing zones on C. violaceum CV026 at MIC (minimal inhibitory concentration) were 10.3 ± 0.8 mm for DCM extract and 12.0 ± 0.5 mm for AcOEt extract. Extracts showed concentration-dependent inhibition of swarming motility on flagellated P. aeruginosa PA01 and at the highest test concentration of 100 µg/mL, AcOEt (35.42 ± 1.00%) extract displayed the best activity. FRAP assay indicated that the BuOH extract (A0.50 = 17.42 ± 0.25 µg/mL) was more active than standard α-tocopherol (A0.50 = 34.93 ± 2.38 µg/mL). BuOH extract was more active than other extracts except in the ABTS●+, where the DCM extract was most active. This antioxidant activity could be attributed to the phenolic compounds detected. C. nepeta extracts showed moderate inhibition on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, and α-amylase. The results indicate that C. nepeta is a potent source of natural antioxidants that could be used in managing microbial resistance and Alzheimer's disease.

Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient's daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aß) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer's disease.

A Preliminary Study of Chemical Profiles of Honey, Cerumen, and Propolis of the African Stingless Bee Meliponula ferruginea.

Recently, the honey and propolis of stingless bees have been attracting growing attention because of their health-promoting properties. However, studies on these products of African Meliponini are still very scarce. In this preliminary study, we analyzed the chemical composition of honey, two cerumen, and two resin deposits (propolis) samples of Meliponula ferruginea from Tanzania. The honey of M. ferruginea was profiled by NMR and indicated different long-term stability from Apis mellifera European (Bulgarian) honey. It differed significantly in sugar and organic acids content and had a very high amount of the disaccharide trehalulose, known for its bioactivities. We suggested trehalulose to be a potential marker for African stingless bee honey analogously to the recent proposal for Meliponini honey from Asia, South America, and Australia and demonstrated its easy discrimination by 13C NMR. Propolis and cerumen were studied by GC-MS (gas chromatography-mass spectometry). The samples contained mainly terpenoids (di-and triterpenes) but demonstrated qualitative and quantitative differences. This fact was an indication that possibly M. ferruginea has no strict preferences for resins used to construct and protect their nests. The antimicrobial and anti-quorum sensing properties of the two materials were also tested. These first results demonstrated that the honey, cerumen, and propolis of African stingless bees were rich in biologically active substances and deserved further research.

Bioactive constituents from seeds of Annona Senegalensis Persoon (Annonaceae).

Column chromatography led to the isolation and full characterization of N-cerotoyltryptamine (1) previously described in a mixture of 5 compounds, asimicin (2) and ent-19-Carbomethoxykauran-17-oic acid (3) isolated from this species for first time alongside stigmasterol glycoside (4) and lacceroic acid (5). The structures of the compounds were established by extensive EIMS, HRESIMS, 1 D and 2 D NMR studies. Compound 1 and the extract AS were more potent inhibitors of ROS with IC50 values of 2.7 ± 0.1 µg/mL and 8.7 ± 10.2 µg/mL respectively than Ibuprofen (11.2 ± 1.9 µg/mL) as a standard anti-inflammatory drug. Compound 2 showed high inhibition on nitric oxide (IC50 = 3.9 ± 0.2 µg/mL), almost 6 times more active than the standard compound L-NMMA (IC50 = 24.2 ± 0.8 µg/mL) used. Compounds showed relatively low toxicity on NIH-3T3 fibroblast cells compared to standard. The results indicate that compounds 1 and 2 are potent anti-inflammatory drug candidates.

Antibiofilm and Enzyme Inhibitory Potentials of Two Annonaceous Food Spices, African Pepper (Xylopia aethiopica) and African Nutmeg (Monodora myristica).

Food pathogens represent an important health threat, and it is relevant to study the effect of foodstuffs such as spices which can inhibit bacterial growth. This study reports the antimicrobial, antibiofilm, and enzyme (Acetylcholinesterase, Butyrylcholinesterase, urease, tyrosinase) inhibitory activities of two medicinal food spices belonging to the Annonaceae family, Monodora myristica and Xylopia aethiopica. GC-MS (gas chromatography mass spectrometry) analysis of silylated samples of Methanol-Dicloromethane (50:50) extracts of both plants led to the identification of nine compounds in M. myristica and seven compounds in X. aethiopica. M. myristica and X. aethiopica had the same minimum inhibitory concentration (MIC) values of 0.625 mg/mL and 2.5 mg/mL on C. albicans and E. coli, respectively. However, M. myristica had better activity than X. aethiopica on Staphylococcus aureus, while Pseudomonas aeruginosa was more susceptible to X. aethiopica than M. myristica. The lowest MIC value was 0.1325 mg/mL, exhibited by M. myristica on S. aureus. Both extracts showed good antibiofilm activity. On S. aureus, at the same concentration, M. myristica had better antibiofilm activity than X. aethiopica. On E. coli and Candida albicans, X. aethiopica had better antibiofilm activity than M. myristica at the same concentration. X. aethiopica showed better violacein inhibition in Chromobacterium violaceum CV12472, as its percentage inhibition of violacein varied from 80.5% ± 3.0% at MIC to 5.6 ± 0.2 at MIC/8, as compared to M. myristica with 75.1% ± 2.5% at MIC and 15.5% ± 1.1% at MIC/8. The anti-motility activity by swimming and swarming inhibition on P. aeruginosa PA01 was low at test concentrations and in both models, M. myristica showed higher motility inhibition than X. aethiopica. Although in enzyme inhibitory assays all extracts had low inhibitions compared to standards tested at the same concentrations, the results show that these plants can be used to manage food-borne infections.

Antibiofilm and anti-quorum sensing activities of polyethylene imine coated magnetite and nickel ferrite nanoparticles.

This study was aimed at synthesizing polyethyleneimine-coated magnetic nanoparticles and evaluating their effect on pathogenic bacteria. Polyethyleneimine-coated magnetite (PEIMnF) and nickel ferrite (PEINF) nanoparticles were succesfully synthesized and their surface groups, morphology and chemical structures were characterized using ATR-FTIR (Attenuated Total Reflectance Fourrier Transformed Infra-Red) and SEM (Scanning Electron Microscopy). TGA (Thermogravimetric analysis) was used to analyse the thermal behaviour and stability of synthesized nanomaterials. The minimal inhibitory concentration (MIC) values of the polyethylene imine coated magnetite and nickel ferrite nanomaterials against Staphylococcus aureus, Escherichia coli and Candida albicans was found to be 10 mg/mL. Both nanomaterials (PEIMnF and PEINF) showed very excellent and concentration-dependent biofilm inhibition especially at the highest test concentration of 10 mg/mL at which PEIMnF inhibited biofilm formation on E. coli (89.04 ± 0.50%), S. aureus (82.85 ± 2.42%) and C. albicans (91.37 ± 0.66%). At this concentration, PEINF equally inhibited biofilm formations of E. coli (90.48 ± 2.05%), S. aureus (87.04 ± 1.59%) and C. albicans (90.94 ± 1.03%). Only PEINF showed a concentration-dependent violacein inhibition with highest inhibition of 51.2 ± 3.5% at MIC and quorum sensing with inhibition zones of 16.3 ± 1.0 mm at MIC and 11.5 ± 0.5 mm at MIC/2 which could be attributed to the presence of nickel. The nanomaterials inhibited swimming and swarming motilities in Pseudomonas aeruginosa PA01 and it was found that at the same concentration, swimming inhibition was greater than swarming inhibitions and PEINF showed better inhibition than PEIMnF in both models. Polyethyleneimine-coated magnetite and nickel ferrite nanomaterials could be used in overcoming health problems associated with microbial infections and resistance.

A new isoflavonol and other constituents from Cameroonian propolis and evaluation of their anti-inflammatory, antifungal and antioxidant potential.

Propolis is rich in diverse bioactive compounds. Propolis samples were collected from three localities of Cameroon and used in the study. Column chromatography separation of propolis MeOH:DCM (50:50) extracts yielded a new isoflavonol, 2-hydroxy-8-prenylbiochanin A (1) alongside 2',3'-dihydroxypropyltetraeicosanoate (2) and triacontyl p-coumarate (3) isolated from propolis for first time together with seven compounds: ß-amyrine (4), oleanolic acid (5), ß-amyrine acetate (6), lupeol (7), betulinic acid (8), lupeol acetate (9) and lupenone (10). These compounds were tested for their inhibitory effect on oxidative burst where intracellular reactive oxygen species (ROS) were produced from zymosan stimulated human whole blood phagocytes and on production of nitric oxide (NO) from lipopolysaccharide (LPS) stimulated J774.2 mouse macrophages. The cytotoxicity of these compounds was evaluated on NIH-3 T3 normal mouse fibroblast cells, antiradical potential on 2,2-diphenyl-1-picrylhydrazylhydrazyl (DPPH·) as well as their anti-yeast potential on four selected candida species. Compound 1 showed higher NO inhibition (IC50 = 23.3 ± 0.3 µg/mL) than standard compound L-NMMA (IC50 = 24.2 ± 0.8 µg/mL). Higher ROS inhibition was shown by compounds 6 (IC50 = 4.3 ± 0.3 µg/mL) and 9 (IC50 = 1.1 ± 0.1 µg/mL) than Ibuprofen (IC50 = 11.2 ± 1.9 µg/mL). Furthermore, compound 1 displayed moderate level of cytotoxicity on NIH-3 T3 cells, with IC50 = 5.8 ± 0.3 µg/mL compared to the cyclohexamide IC50 = 0.13 ± 0.02 µg/mL. Compound 3 showed lower antifungal activity on Candida krusei and Candida glabrata, MIC of 125 µg/mL on each strain compared to 50 µg/mL for fuconazole. The extracts showed low antifungal activities ranging from 250 to 500 µg/mL on C. albicans, C. krusei and C. glabrata and the values of MIC on Candida parapsilosis were 500 µg/mL and above. DPPH* scavenging activity was exhibited by compounds 1 (IC50 = 15.653 ± 0.335 µg/mL) and 3 (IC50 = 89.077 ± 24.875 µg/mL) compared to Vitamin C (IC50 = 3.343 ± 0.271 µg/mL) while extracts showed moderate antiradical activities with IC50 values ranging from 309.31 ± 2.465 to 635.52 ± 11.05 µg/mL. These results indicate that compounds 1, 6 and 9 are potent anti-inflammatory drug candidates while 1 and 3 could be potent antioxidant drugs.