Novel Signposts on the Road from Natural Sources to Pharmaceutical Applications: A Combinative Approach between LC-DAD-MS and Offline LC-NMR for the Biochemical Characterization of Two Hypericum Species (H. montbretii and H. origanifolium).

The members of the genus Hypericum have great potential to develop functional uses in nutraceutical and pharmaceutical applications. With this in mind, we aimed to determine the chemical profiling and biological properties of different extracts (ethyl acetate, methanol and water) from two Hypericum species (H. montbretii and H. origanifolium). We combined two approaches (LC-DAD-MS and LC-NMR) to identify and quantify chemical compounds of the extracts. Antioxidant properties (free radical quenching, reducing power and metal chelating) and enzyme inhibitory effects (cholinesterase, tyrosinase, amylase and glucosidase) were determined as biological properties. The tested extracts were rich in caffeic acid derivatives and flavonoids, and among them, 3-caffeoyl quinic acid and myricetin-3-O-rhamnoside were found to be the main compounds. The total phenolic and flavonoid levels were determined to be 50.97-134.99 mg GAE/g and 9.87-82.63 mg RE/g, respectively. With the exception of metal chelating, the methanol and water extracts showed stronger antioxidant properties than the ethyl acetate extracts. However, different results were obtained for each enzyme inhibition assay, and in general, the ethyl acetate extracts present more enzyme-inhibiting properties than the water or methanol extracts. Results from chemical and biological analyses were combined using multivariate analysis, which allowed establishing relationships between composition and observed effects of the Hypericum extracts based on the extraction solvents. To gain more insights between chemical compounds and enzyme-inhibiting effects, we performed molecular docking analysis. We observed favorable interactions between certain compounds and the tested enzymes during our analysis, confirming the data obtained from the multivariate approach. In conclusion, the obtained results may shed light on the road from natural sources to functional applications, and the tested Hypericum species may be considered potential raw materials, with promising chemical constituents and biological activities.

Bridging the Chemical Profiles and Biological Effects of Spathodea campanulata Extracts: A New Contribution on the Road from Natural Treasure to Pharmacy Shelves.

Spathodea campanulata is an important medicinal plant with traditional uses in the tropical zone. In the current work, we aimed to determine the chemical profiles and biological effects of extracts (methanolic and infusion (water)) from the leaves and stem bark of S. campanulata. The chemical components of the tested extracts were identified using LC-ESI-QTOF-MS. Biological effects were tested in terms of antioxidant (radical scavenging, reducing power, and metal chelating), enzyme inhibitory (cholinesterase, amylase, glucosidase, and tyrosinase), antineoplastic, and antiviral activities. Fifty-seven components were identified in the tested extracts, including iridoids, flavonoids, and phenolic acids as the main constituents. In general, the leaves-MeOH extract was the most active in the antioxidant assays (DPPH, ABTS, CUPRAC, FRAP, metal chelating, and phosphomolybdenum). Antineoplastic effects were tested in normal (VERO cell line) and cancer cell lines (FaDu, HeLa, and RKO). The leaf infusion, as well as the extracts obtained from stem bark, showed antineoplastic activity (CC50 119.03-222.07 µg/mL). Antiviral effects were tested against HHV-1 and CVB3, and the leaf methanolic extract (500 µg/mL) exerted antiviral activity towards HHV-1, inhibiting the viral-induced cytopathic effect and reducing the viral infectious titre by 5.11 log and viral load by 1.45 log. In addition, molecular docking was performed to understand the interactions between selected chemical components and viral targets (HSV-1 DNA polymerase, HSV-1 protease, and HSV-1 thymidine kinase). The results presented suggest that S. campanulata may be a bright spot in moving from natural sources to industrial applications, including novel drugs, cosmeceuticals, and nutraceuticals.

LC-MS Based Analysis and Biological Properties of Pseudocedrela kotschyi (Schweinf.) Harms Extracts: A Valuable Source of Antioxidant, Antifungal, and Antibacterial Compounds.

The impact of two extraction solvents on the phenolic composition, antioxidant, and enzymes inhibitory and antimicrobial activities of two parts (leaves and stem bark) of P. kotschyi was studied. Two different LC-DAD-MSn approaches were used to identify and quantify the bioactive compounds in the different extracts. A total of thirty-two compounds were quantified, being the procyanidin the most abundant in stem bark while catechin and flavonoids are most abundant in leaves. Overall, the stem bark extraction using methanol showed higher amounts of total phenolic (131.83 ± 1.81 mg GAE/g) and flavanol (14.14 ± 0.11 mg CE/g) while the leaves extraction using water exhibited stronger levels of total flavonoid (44.95 ± 0.38 mg RE/g) and phenolic acid (63.58 ± 2.00 mg CAE/g). As regards the antioxidant assays, methanol stem bark extracts were characterized by the highest antioxidant activities (DPPH: 1.94 ± 0.01 mmol TE/g, ABTS: 3.31 ± 0.01 mmol TE/g, FRAP: 2.86 ± 0.02 mmol TE/g, CUPRAC: 5.09 ± 0.08 mmol TE/g, phosphomolybdenum: 5.16 ± 0.23 mmol TE/g and metal chelating: 17.12 ± 0.46 mg EDTAE/g). In addition, the methanolic extracts of stem bark had highest impact on acetylcholinesterase (2.54 mg GALAE/g), butyrylcholinesterase (5.48 mg GALAE/g). In contrast, the methanolic extracts of leaves was potent against tyrosinase (77.39 ± 0.21 mg KAE/g) and α-glucosidase (0.97 ± 0.01 mmol ACAE/g), while a higher anti-α-amylase (0.97 ± 0.01 mmol ACAE/g) was observed for water extracts of the same part. All of the tested extracts showed inhibitory effects on elastase, except methanolic leaves extracts. Additionally, the extracts exhibited appreciable antifungal toward A. ochraceus, A. fumigatus, P. ochrochloron, T. viride, and P. funiculosum and promising antibacterial activity against M. flavus, S. aureus, L. monocytogenes, E. coli, P. aeruginosa, E. cloacae, and S. typhimurium. Taken together, the outcomes demonstrated P. kotschyi as a novel source of bioactive molecules of interest with an evident therapeutic value.

Chemical Profiling and Biological Evaluation of Nepeta baytopii Extracts and Essential Oil: An Endemic Plant from Turkey.

Nepeta baytopii is a poorly studied, endemic Nepeta species (Lamiaceae) of Turkey. For the first time, the biological activities (antioxidant, enzyme inhibition, and cytotoxicity properties) of the hexane, ethyl acetate, methanol, water/methanol, and water extracts and essential oil prepared from N. baytopii aerial parts were assessed. Hydro-methanol (41.25 mg gallic acid equivalent (GAE)/g) and water extracts (50.30 mg GAE/g), respectively showed the highest radical scavenging (94.40 and 129.22 mg Trolox equivalent (TE)/g, for 2,2-diphenyl-1-picrylhydrazyl radical and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid radical scavenging assays) and reducing (229.37 and 129.55 mg TE/g, for ferric-reducing antioxidant power and cupric-reducing antioxidant capacity assays) capacities in vitro. An interestingly high inhibition was observed for ethyl acetate extract against butyrylcholinesterase (10.85 mg galantamine equivalent/g). The methanol extract showed high cytotoxicity (31.7%) against HepG2 cells. Caryophyllene oxide was identified in high concentrations in the essential oil (39.3%). Luteolin and apigenin and their derivatives were identified from the methanol and water extracts. The results obtained from this study highlighted that the abundance of highly bioactive compounds from Nepeta baytopii ensures the multiple biological activities of the tested extracts, and this suggests a potential use in the pharmaceutical and nutraceutical fields, and therefore should be investigated further.

NMR and LC-MSn coupled with pharmacological network analysis for the assessment of phytochemical content and biopharmaceutical potential of Carapa procera extracts.

The methanolic and water extracts of Carapa procera leaves and stem barks were screened for their phytochemical content using a multi-technique approach. The extracts were also assessed for their in vitro antioxidant capacity along with their anti-diabetic (α-amylase, α-glucosidase), anti-tyrosinase, anti-elastase and anti-cholinesterase (AChE, BChE) activities. Furthermore, antibacterial and antifungal effects were determined against several bacterial and fungal strains. Data Integration Analysis for Biomarker discovery using Latent components (DIABLO) integrative analysis was conducted on collected data to determine the influence of extraction solvents and plant parts on phytochemical content, antioxidant properties and enzyme inhibitory properties of C. procera samples. Additionally, the major identified compounds were screened as modulators of multiple pathways involved in human diseases via Gene Ontology (GO) enrichment analysis. Results showed that methanolic stem bark extract exhibited the most potent ABTS scavenging, Cu2+ and Fe3+ reducing power, total antioxidant capacity and Fe2+ chelating power and displayed the highest total flavanol content. Methanolic extracts of leaves and stem barks were abounded with phenolics and had the greatest anti-AChE, anti-BChE, anti-tyrosinase and anti-elastase activities. A significant antifungal activity was observed, with the lowest minimum inhibitory concentration and minimum fungicidal values of 0.07 and 0.15 mg/mL, respectively. DIABLO integrative analysis suggested that the phytochemical content and biological activities varied significantly within the plant parts and were influenced by types of solvent used. GO enrichment analysis on the main bioactive compounds showed modulation of multiple pathways associated with cancer. Obtained results demonstrated that stem bark and leaves of C. procera can be considered as promising sources of bioactive molecules with high pharmacological values.

A Prospective of Multiple Biopharmaceutical Activities of Procyanidins-Rich Uapaca togoensis Pax Extracts: HPLC-ESI-TOF-MS Coupled with Bioinformatics Analysis.

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application.

HPLC-DAD-UV analysis, anti-inflammatory and anti-neuropathic effects of methanolic extract of Sideritis bilgeriana (lamiaceae) by NF-κB, TNF-α, IL-1ß and IL-6 involvement.

Medicinal plants remain an invaluable source for therapeutics of diseases that affect humanity. Sideritis bilgeriana (Lamiaceae) is medicinal plant used in Turkey folk medicine to reduce inflammation and pain, but few studies scientific corroborates its medicinal use so creating a gap between popular use and scientific evidence. Thus, we aimed to evaluate the pharmacological effects of the methanolic extract of S. bilgeriana (MESB) in rodents nociception models and also performed its phytochemical analysis. Firstly, a screening was carried out that enabled the identification of the presence of phenolic compounds and flavonoids. In view of this, a chromatographic method by HPLC-DAD-UV was developed that made it possible to identify chlorogenic acid and its quantification in MESB. MESB-treated mice (MESB 50, 100 and 200 mg/kg, p.o.) reduced mechanical hyperalgesia and myeloperoxidase activity (p < 0.01), and also showed a reduced pain behavior in capsaicin test. In the carrageenan-induced pleurisy test, MESB (100 mg/kg p.o.) significantly reduced the leukocyte (polymorphonuclear) count in the pleural cavity and equally decreased the TNF-α and IL-1ß levels (p < 0.001). In the PSNL model, mechanical hyperalgesia was reduced on the first evaluation day and during the 7 days of evaluation compared to the vehicle group (p < 0.001). Thermal hyperalgesia was also reduced 1 h after treatment compared to the vehicle group (p < 0.001) and reversed the loss of force initially displayed by the animals, thus inferring an analgesic effect in the muscle strength test. Analysis of the marrow of these animals showed a decrease in the level of pro-inflammatory cytokine IL-6 (p < 0.001) and factor NF-κB, in relation to the control group (p < 0.05). Moreover, the MESB treatment produced no noticeable side effects, no disturb in motor performance and no signs of gastric or hepatic injury. Together, the results suggests that MESB could be useful to management of inflammation and neuropathic pain mainly by the management of pro-inflammatory mediators (NF-κB, TNF-α, IL-1ß and IL-6), so reinforcing its use in popular medicine and corroborating the need for further chemical and pharmacological studies for the species.

Network analysis, chemical characterization, antioxidant and enzyme inhibitory effects of foxglove (Digitalis cariensis Boiss. ex Jaub. & Spach): A novel raw material for pharmaceutical applications.

The present study outlines the phenolic composition and pharmacological properties of different extracts of Digitalis cariensis Boiss. ex Jaub. & Spach root and aerial parts. The metabolic profiles of the studied extracts were characterized by UHPLC-MS. The in vitro antioxidant and enzyme (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase) inhibitory potential of the extracts were determined. Bioinformatics and docking investigations were also conducted to support the enzyme inhibition test and predict putative targets for potential pharmacological applications. Overall, the methanolic extract followed by the water extract of the D. cariensis root were found to be superior source of antioxidant compounds except for metal chelating ability, in which the water extract of the root (26.34 ± 1.54 mg EDTAE/g) and aerial parts (16.47 ± 0.88 mg EDTAE/g) have showed the highest activity. The tested extracts were potent against AChE (9.11 ± 0.27-9.79 ± 0.28 mg GEs/g extract), α-amylase (0.12 ± 0.01- 0.50 ± 0.01 mmol ACEs/g extract) and α-glucosidase (0.28 ± 0.01-17.29 ± 0.24 mmol ACEs/ g extract). Notable activity against tyrosinase was displayed by the methanolic extracts (Root-MeOH: 123.71 ± 2.70 and aerial parts - MeOH: 137.96 ± 1.07 mg KAE/g extract), while none of the extracts were potent against BChE. According to docking investigations, the observed anti-tyrosinase effect could be related, at least partially, to the presence of luteolin, rosmarinic acid and kaempferol in the extracts. Results amassed herein is the first report on the biological attributes of D. cariensis, which validate the pharmacological uses of this plant.

Metabolomics profiling and biological properties of root extracts from two Asphodelus species: A. albus and A. aestivus.

The pharmacological properties of Asphodelus species have been advocated previously. In this respect, the present study attempts to unravel the antioxidant and enzyme inhibitory activity of root extracts of two Asphodelus species, namely, A. albus and A. aestivus. Data gathered demonstrated that the dichloromethane (25.49, 51.30, 104.31, and 81.58 mg Trolox equivalents [TEs]/g, for 2,2-diphenyl-1-picrylhydrazyl [DPPH], 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) [ABTS], cupric ion reducing antioxidant capacity [CUPRAC], and ferric reducing antioxidant power[FRAP] assays respectively) and ethyl acetate (20.60, 41.86, 89.07, and 57.85 mg TEs/g, for DPPH, ABTS, CUPRAC, and FRAP assays respectively) extracts of A. albus roots showed highest radical scavenging and reducing potential. These findings were in accordance with total phenolic content observed which showed the highest phenolic content of A. albus dichloromethane (30.74 mg gallic acid equivalents [GAEs]/g) and ethyl acetate (23.41 mg GAEs/g) extracts. Interestingly, A. albus and A. aestivus root extracts were active inhibitors of tyrosinase and lipase, with values varying from 56.52 to 71.49 mg kojic acid equivalent/g and 34.88 to 86.32 mg orlistat equivalent/g, respectively. Flavonoids, anthraquinones, and phenolic acids were identified as main individual compounds in chemical profile analysis. This is the first report of the presence of aloin A, aloin B, and aloesin in species other than in Aloe. Scientific evidences gathered from this study claimed the biological activity of the studied Asphodelus species and provided rationale for further investigations which might lead to the development of novel pharmacophores to alleviate oxidative stress related complications, obesity, as well as, skin hyperpigmentation complications.

Novel insights into the fruit and seed extracts of Morinda morindoides (Baker) Milne-Redh: HPLC-ESI-Q-TOF-MS profiling, antioxidant, and enzyme inhibitory propensities.

In this study, we attempted for the first time to determine the phytochemical compositions and biopharmaceutical properties of the methanolic and aqueous extracts of Morinda morindoides fruits and seeds. Antioxidant propensities of the extracts were determined via free radical-scavenging, phosphomolybdenum, metal chelating, and reducing power assays. Inhibitory activities against cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), tyrosinase, α-amylase, and α-glucosidase were assessed. Moreover, the total phenolic and flavonoid contents were determined. High Performance Liquid Chromatography coupled to Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESI-Q-TOF-MS) analysis was performed to establish the chemical profile of the investigated extracts. The tested extracts showed remarkable antioxidant abilities with aqueous fruit extract being most potent in all assays, except for ferrous ion chelating assay. Overall, the methanolic extracts were potent inhibitors of the tested enzymes. In conclusion, M. morindoides may be endorsed as promising sources of bioactive compounds and used for designing functional foods. PRACTICAL APPLICATIONS: In recent years, new compounds from plant sources have attracted great interest to design functional foods. Thus, we aimed to detect biological and chemical properties of Morinda morindoides fruits and seeds, a widely used as food with medicinal properties in Africa. Based on our findings, fruits extracts exhibited stronger activity when compared to seed extracts. Also, chemical identification was performed for each extracts. The presented findings could provide valuable information into the pool of scientific knowledge and may be basis for the design of novel functional applications from M. morindoides.

Chemical profiling and pharmaco-toxicological activity of Origanum sipyleum extracts: Exploring for novel sources for potential therapeutic agents.

The phytochemical, antiradical, and enzyme inhibition profile of three solvent extracts (ethyl acetate, methanol, water) of Origanum sipyleum were assessed. We also performed a pharmacological study in order to explore protective effects induced by extracts in inflamed colon. LC-MS analysis revealed that the extracts contained different classes of phenolics. The aqueous extract showed the highest antioxidant and acetylcholinesterase (AChE) inhibitory effects. Total phenol and flavonoid contents were highest in aqueous and ethyl acetate extract, respectively. All extracts were effective in reducing colon pro-oxidant and pro-inflammatory biomarkers. The extracts revealed also able to inhibit fungal and bacterial species involved in ulcerative colitis, including Candida albicans, Candida tropicalis, Staphylococcus aureus, and Staphylococcus thyphimurium. Finally, we also showed the antiproliferative effects exerted by the EA extracts on human colon cancer HCT116 cell line. Concluding, our results indicated that O. sipyleum extracts displayed promising therapeutic properties which warrants further validation. PRACTICAL APPLICATIONS: The present phytochemical and biological studies, including antioxidant, anti-inflammatory, and antimicrobic assessments, showed significant protective effects exerted by O. sipyleum extracts in an experimental model of ulcerative colitis. The results are intriguing and suggest potential applications O. sipyleum extracts as sources of natural agents for the management of clinical symptoms related to ulcerative colitis, characterized by increased burden of oxidative stress and microbiome dysbiosis.

Chemical fingerprints, antioxidant, enzyme inhibitory, and cell assays of three extracts obtained from Sideritis ozturkii Aytaç & Aksoy: An endemic plant from Turkey.

This study was geared towards assessing the possible antioxidant, enzyme inhibitory, and cytotoxic activities of ethyl acetate, methanol, and water extracts of Sideritis ozturkii Aytaç & Aksoy. The phytochemical profiles of the studied extracts were characterised by HPLC-MS/MS. The methanol extract, rich in phenolics (78.04 mg gallic acid equivalent/g), exhibited the strongest antioxidant activities. However, the ethyl acetate extract was the most active extract in the enzyme inhibitory assays. The water extract of S. ozturkii (1 mg/ml, 48 h incubation) slightly inhibited (22%) growth of human breast cancer cell line (MDA-MB-231 cells). On the other hand, the ethyl acetate and methanol extracts showed strong inhibition (98% and 97%, respectively) of MDA-MB-231 cells and caused apoptotic cell death. Scientific data generated from this study further appraises the multiple biological activities of plants belonging to the Sideritis genus. In addition, preliminary evidence gathered from the current investigation advocates for further studies geared towards the preparation of therapeutic formulations from S. ozturkii.

Chemical profile, antioxidant, and enzyme inhibitory properties of two Scutellaria species: S. orientalis L. and S. salviifolia Benth.

OBJECTIVES: This study investigates into the biological effects of solvent extracts (ethyl acetate, methanol, and water) of Scutellaria orientalis L. and Scutellaria salviifolia Benth. based on its enzyme inhibitory activity and antioxidant ability together with the screening of bioactive compounds. METHODS: Total and individual bioactive components were determined using spectrophotometric and HPLC-ESI-MS methods. Six antioxidant assays were conducted and enzyme inhibition was tested against key enzymes linked to the pathology of common chronic disorders. KEY FINDINGS: Results revealed that the aqueous extracts of both plants exerted better 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid scavenging, reducing power, metal chelating, and α-glucosidase inhibitory activities. The methanol extracts showed highest tyrosinase inhibition and antioxidant activity in phosphomolybdenum assay while the less polar ethyl acetate extracts showed better acetylcholinesterase, butyrylcholinesterase, and α-amylase inhibition. Phytochemical evaluation by HPLC-ESI-MS revealed the presence of high amounts of flavones. CONCLUSIONS: Scutellaria orientalis and S. salviifolia are important sources of bioactive agents that warrants further studies.

Biological, chemical and in silico fingerprints of Dianthus calocephalus Boiss.: A novel source for rutin.

Extracts (methanol, ethyl acetate, and water) from Dianthus calocephalus Boiss. prepared by different extraction techniques (maceration, Soxhlet, and ultrasonication) were studied for possible inhibitory action against key enzymes (α-amylase, α-glucosidase, acetyl cholinesterase, butyryl cholinesterase, and tyrosinase). Antioxidant potential was established using a battery of assays and phenolic compounds profiled by RP-HPLC. Binding pose of tyrosinase with rutin was studied by means of molecular docking. Methanol extracts showed the highest phenolic (39.35-40.25 mgGAE/g) content and rich in rutin (61.38-72.07 mg/g extract). Ethyl acetate extracts of D. calocephalus were potent inhibitors of acetyl (1.45-1.48 mgGALAE/g) and butyryl (2.44-2.74 mgGALAE/g) cholinesterases. Docking studies showed that rutin interacts with the side chains of the key amino acid residues and to the copper atom found at the active site of tyrosinase. Methanol extracts showed highest antioxidant capacity. D. calocephalus showed interesting biological properties that could be further studied to manage diabetes, neurodegenerative diseases, Alzheimer's disease, and hyperpigmentation.

Biological effects and chemical characterization of Iris schachtii Markgr. extracts: A new source of bioactive constituents.

This study gathers information about the effects of different extracts (methanol and water) from rhizomes and aerial parts of Iris schachtii on selected enzymes (cholinesterases, alpha-amylase and alpha-glucosidase, tyrosinase and lipase) as well as of their antioxidant capacities and antimutagenic properties in relation with their phenolic composition. The chemical composition was assessed by determining total phenolic and flavonoid content as well as individual phenolic compounds by HPLC-DAD. Moreover, antioxidant abilities of the investigated extracts were tested by using different assays including free radical scavenging (DPPH and ABTS), reducing power (CUPRAC and FRAP), phosphomolybdenum and metal chelating, overall rhizomes being indicated as a superior source of antioxidant compounds. HPLC analysis revealed the abundance of some phenolics including apigenin (2584 µg/g extract) and luteolin (2510 µg/g extract) in aerial parts extracts while rhizomes were rich in apigenin (4734 µg/g extract) and kaempferol (4214 µg/g extract). The methanolic extracts exhibited a high anti-lipase activity while all extracts presented a relatively high inhibition on α-glucosidase. Furthermore, interactions between dominant compounds from extracts and selected enzymes were investigated by molecular modeling studies in order to explain at a molecular level the interactions between selected compounds and active sites of the enzyme/s.

Design, synthesis and biochemical evaluation of novel multi-target inhibitors as potential anti-Parkinson agents.

New 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives are proposed as dual-target-directed monoamine oxidase B (MAO-B) and acetylcholinesterase (AChE) inhibitors, as well as antioxidant agents, for the treatment of neurodegenerative disorders such as Parkinson's disease. Rational molecular design, target recognition and predicted pharmacokinetic properties have been evaluated by means of molecular modelling. Based on these properties, compounds were synthesized and evaluated in vitro as MAO-B and AChE inhibitors, and compared to the activities at their corresponding isozymes, monoamine oxidase A (MAO-A) and butyrylcholinesterase (BuChE), respectively. Anti-oxidant properties, potentially useful in the treatment of neurodegenerative disorders, have been also investigated in vitro. Among the evaluated compounds, three inhibitors may be considered as promising dual inhibitors of MAO-B and AChE, in vitro. MAO-B inhibition was also shown to be competitive and reversible for compound 19.

Identification of phenolic components via LC-MS analysis and biological activities of two Centaurea species: C. drabifolia subsp. drabifolia and C. lycopifolia.

The Centaurea genus has great potential in traditional systems and has attracted much interest in the design of novel drug formulations. The present study was focused on the chemical fingerprints and biological properties of Centaurea drabifolia subsp. drabifolia and Centaurea lycopifolia extracts. Spectrophotometric and LC-MS techniques were used to establish the chemical profiles of the studied extracts. Enzyme inhibitory potential was assessed against key enzymes linked to global health problems, namely neurodegenerative diseases (acetylcholinesterase), pigmentation (tyrosinase), and diabetes (α-amylase and α-glucosidase). The antimicrobial propensities of the extract were evaluated against 16 bacterial and fungal strains using the microdilution method. The antioxidant abilities were assessed using DPPH and ABTS radical scavenging, ferric, and cupric reducing powers, phosphomolybdenum, and ferrous metal chelation. The total phenolic compounds varied from 18.33 to 32.84mgGAE/g extract. Total flavonoid content of the extracts were in the range of 2.88-22.39mgRE/g extract. Methanol and water extracts showed stronger antioxidant abilities compared to the ethyl acetate extracts. However, the latter extracts were most efficient towards the target enzymes (except for tyrosinase). The water extracts also exerted considerable antimicrobial effects. Findings from the present work tend to support the idea that C. drabifolia subsp. drabifolia and C. lycopifolia may be utilized as effective bio-resources for designing novel health-promoting products or ingredients. It is anticipated that results amassed from this still will open new avenues for research and contribute towards establishing primary data on these species for designing novel phytopharmaceuticals.

A Multidirectional Perspective for Novel Functional Products: In vitro Pharmacological Activities and In silico Studies on Ononis natrix subsp. hispanica.

The genus Ononis has important value as traditional drugs and foods. In the present work, we aimed to assess the chemical profiles and biological effects of Ononis natrix subsp. hispanica extracts (ethyl acetate, methanol, and water). For chemical profile, total and individual phenolic components were detected. For biological effects, antioxidant (DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays), enzyme inhibitory (against cholinesterase, tyrosinase, α-amylase and α-glucosidase), antimicrobial, DNA protection and cytotoxic abilities were tested. The predominant phenolics were apigenin, luteolin, and quercetin in the tested extracts. Generally, the ethyl acetate and methanol extracts were noted as the most active in the antioxidant and enzyme inhibitory assays. Water extract with different concentrations indicated high level of DNA protection activity. Methanol and ethyl acetate extracts showed antibacterial effect against to Staphylococcus aureus and Staphylococcus epidermidis strains. The cytotoxic effects of O. natrix subsp. hispanica extracts on the survival of HeLa and PC3 cells were determined by MTT cell viability assay. Water and methanol extracts caused initiation of apoptosis for PC3 cell line. Furthermore, molecular docking was performed to better understand interactions between dominant phenolic compounds and selected enzymes. Our results clearly indicate that O. natrix subsp. hispanica could be considered a potential candidate for designing novel pharmaceuticals, cosmeceuticals and nutraceuticals.

Antioxidant and Enzyme Inhibitory Activities of Extracts from Wild Mushroom Species from Turkey.

The antioxidant and inhibitory effects of methanol and aqueous extracts from Hymenogaster aromaticus, Ramaria aurea, and Rhizopogon luteolus against cholinesterase, tyrosinase, α-amylase, and α-glucosidase are reported here, to our knowledge for the first time. Antioxidant activities were investigated using different assays, including 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ferric ion-reducing antioxidant power, cupric ion-reducing antioxidant capacity, phosphomolybdenum, and metal-chelating assays. In general, the highest antioxidant and enzyme-inhibitory effects were observed in methanol extracts, which had the highest concentrations of phenolics. (+)-Catechin, benzoic acid, and p-hydroxybenzoic acid were determined to be the main phenolics in H. aromaticus components both in methanol and in aqueous extracts, whereas the other 2 species present very different phenolic fingerprints, also at smaller quantities. These results suggest that these mushroom species may be considered sources of natural agents.

Cytotoxic and Enzyme Inhibitory Potential of Two Potentilla species (P. speciosa L. and P. reptans Willd.) and Their Chemical Composition.

In this work, the biological and chemical fingerprints of three extracts (ethyl acetate, methanol, and water) from two Potentilla species (Potentilla reptans and P. speciosa) were investigated. Antioxidant, enzyme inhibitory, and cytotoxic activities were performed for the biological fingerprint. For the chemical characterization, total bioactive components, and individual phenolic components were determined using photometric and HPLC methods, respectively. The main identified phenolic compounds in these extracts were rutin and catechin. Methanol and water extracts contained the highest total phenolic and flavonoid content. The results of antioxidant assays showed that methanol and water extracts displayed higher antioxidant activity compared to the ethyl acetate extract. Generally, methanol and water extracts exhibited higher biological activities correlated with higher levels the bioactive components. For P. speciosa, the methanol extract exhibited the highest enzyme inhibitory activity (except BChE inhibitory activity). P. reptans exhibited also high antiproliferative activity against MCF-7 cells whilst P. speciosa had weak to moderate activity against both of A549 and MCF-7 cell lines. The results suggest that Potentilla species could be potential candidates for developing new phyto-pharmaceuticals and functional ingredients.