The present study was designed to evaluate the chemical composition, antioxidant, enzyme inhibition and cytotoxic properties of different extracts from aerial parts of
(family Scrophulariaceae), a ...plant that is native to Lebanon, Syria and Turkey. Six extracts, namely, hexane, dichloromethane (DCM), ethyl acetate (EtOAc), ethanol (EtOH), 70% EtOH, and water (aqueous) were prepared by maceration. The EtOH extract was predominated by the presence of rutin (4280.20 μg g
) and
-coumaric acid (3044.01 μg g
) while the highest accumulation of kaempferol-3-glucoside (1537.38 μg g
), caffeic acid (130.13 μg g
) and 4-hydroxy benzoic acid (465.93 μg g
) was recorded in the 70% EtOH, aqueous, and EtOAc extracts, respectively. The EtOH (46.86 mg TE/g) and 70% EtOH (46.33 mg TE/g) extracts displayed the highest DPPH radical scavenging result. Both these extracts, along with the aqueous one, exerted the highest ABTS radical scavenging result (73.03-73.56 mg TE/g). The EtOH and 70% EtOH extracts revealed the most potent anti-AChE (2.66 and 2.64 mg GALAE/g) and anti-glucosidase (1.07 and 1.09 mmol ACAE/g) activities. The aqueous extract was the most efficacious in inhibiting the proliferation of prostate cancer (DU-145) cells with an IC
of 8.71 μg/mL and a Selectivity Index of 3.7. In conclusion, this study appraised the use of
aerial parts as a potential therapeutic source for future development of phytopharmaceuticals that target specific oxidative stress-linked diseases including diabetes, cancer, cardiovascular disease, and Alzheimer's disease among others.
This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of
L. (Amaryllidaceae)-the medicinal plant that was ...traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical analysis of nine different extracts was performed by UHPLC(-)HESI-QqQ-MS/MS. Antimicrobial and antibiofilm activities of the extracts were investigated on sixteen clinical isolates of bacteria, yeasts and dermatomycetes, all isolated from infected human skin and corneal formations. Cytotoxicity and wound-healing properties were tested on human immortalized keratinocytes (HaCaT cell line). Antioxidant activity was assessed by six different assays, while beneficial potential against certain neurodegenerative diseases and type 2 diabetes was determined in selected enzyme inhibition assays coupled with molecular modeling. The results showed that the obtained extracts were rich in phenolic compounds, especially flavonoid glycosides such as rutin and kaempferol 3-
-glucoside. All of the extracts showed antimicrobial, wound-healing, antioxidant and anti-enzymatic properties. This study is the first of its kind, linking the medieval medicinal use of wild-growing flowers of
with contemporary in vitro scientific approaches.
In this study, six extracts of Arabis carduchorum prepared from solvents of varying polarity (water, methanol, ethyl acetate, dichloromethane, and n-hexane) were investigated for their chemical ...profiles and total phenolic and flavonoid contents (TPC/TFC) using HPLC–MS/MS and spectrophotometric/colorimetric assays, respectively, along with the assessment of their antioxidant and enzyme inhibitory effects. In general, the polar extracts (methanol, water, and infusion) showed higher TPC/TFC than the other extracts (range: 13.73–26.62 mg GAE/g; 2.66–52.95 mg RE/g, respectively). The total antioxidant capacity of the polar extracts ranged from 0.90–1.85 mmol TE/g in phosphomolybdenum assay, while the free radical scavenging potential ranged from 4.36–32.13 mg TE/g and 12.58–67.73 mg TE/g in DPPH and ABTS assays, respectively. While the water and infuse extract inhibited only butyrylcholinesterase (2.68 and 2.39 mg GALAE/g, respectively), the other extracts were found to inhibit both acetyl- and butyryl-cholinesterases (0.96–2.73 mg GALAE/g and 1.86–5.11 mg GALAE/g, respectively). On the contrary, all extracts exhibited anti-tyrosinase (40.24–59.22 mg KAE/g) and anti-amylase (0.09–0.63 mmol ACAE/g) activities. Overall, this study highlighted the effect of solvent polarity on the extraction of bioactive compounds and the biological properties of the extracts of A. carduchorum; hence, the results obtained could be used to guide optimum extraction in future studies.
The members of the genus
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
species
and
). 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-
-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
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
species may be considered potential raw materials, with promising chemical constituents and biological activities.
The biological activity of the aerial part and rhizomes of Primula auriculata were assessed for the first time. The biological activities (antioxidant properties, enzyme inhibition, and AGE ...inhibition) as well as the phenolic and flavonoid contents of the ethyl acetate, ethanol, hydro-ethanol and water extracts of P. auriculata aerial parts and rhizomes were determined. Cell viability assays and gelatin zymography were also performed for MMP-2/-9 to determine the molecular mechanisms of action. The gene expression for MMPs was described with RT-PCR. The levels of various proteins, including phospho-Nf-κB, BCL-2, BAX, p-53, and cyclin D1 as well as RAGE were measured using Western blot analysis. The hydro-ethanol extract of the aerial part possessed the highest phenolic (56.81 mg GAE/g) and flavonoid (63.92 mg RE/g) contents. In-depth profiling of the specialized metabolites by ultra-high-performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS) allowed for the identification and annotation of 65 compounds, including phenolic acids and glycosides, flavones, flavonols, chalcones, dihydrochalcones, and saponins. The hydro-ethanol extract of the aerial parts (132.65, 180.87, 172.46, and 108.37 mg TE/g, for the DPPH, ABTS, CUPRAC, and FRAP assays, respectively) and the ethanol extract of the rhizomes (415.06, 638.30, 477.77, and 301.02 mg TE/g, for the DPPH, ABTS, CUPRAC, and FRAP assays, respectively) exhibited the highest free radical scavenging and reducing activities. The ethanol and hydro-ethanol extracts of both the P. auriculata aerial part and rhizomes exhibited higher inhibitory activity against acetylcholinesterase, while the hydro-ethanol extracts (1.16 mmol ACAE/g, for both the aerial part and rhizomes extracts) were more active in the inhibition of α-glucosidase. After the treatment of an HT-29 colorectal cancer cell line with the extracts, the apoptosis mechanism was initiated, the integrity of the ECM was remodeled, and cell proliferation was also taken under control. In this way, Primula extracts were shown to be potential drug sources in the treatment of colorectal cancer. They were also detected as natural MMP inhibitors. The findings presented in the present study appraise the bioactivity of P. auriculata, an understudied species. Additional assessment is required to evaluate the cytotoxicity of P. auriculata as well as its activity in ex vivo systems.
Histone deacetylases (HDACs) have gained increased attention as targets for anticancer drug design and development. HDAC inhibitors have proven to be effective for reversing the malignant phenotype ...in HDAC-dependent cancer cases. However, lack of selectivity of the many HDAC inhibitors in clinical use and trials contributes to toxicities to healthy cells. It is believed that, the continued identification of isoform-selective inhibitors will eliminate these undesirable adverse effects - a task that remains a major challenge to HDAC inhibitor designs. Here, in an attempt to identify isoform-selective inhibitors, a large compound library containing 2,703,000 compounds retrieved from Otava database was screened against class I HDACs by exhaustive approach of structure-based virtual screening using rDOCK and Autodock Vina. A total of 41 compounds were found to show high-isoform selectivity and were further redocked into their respective targets using Autodock4. Thirty-six compounds showed remarkable isoform selectivity and passed drug-likeness and absorption, distribution, metabolism, elimination and toxicity prediction tests using ADMET Predictor™ and admetSAR. Furthermore, to study the stability of ligand binding modes, 10 ns-molecular dynamics (MD) simulations of the free HDAC isoforms and their complexes with respective best-ranked ligands were performed using nanoscale MD software. The inhibitors remained bound to their respective targets over time of the simulation and the overall potential energy, root-mean-square deviation, root-mean-square fluctuation profiles suggested that the detected compounds may be potential isoform-selective HDAC inhibitors or serve as promising scaffolds for further optimization towards the design of selective inhibitors for cancer therapy.
The present study was performed to determine the chemical constituents, cytotoxicity, antioxidant and enzyme inhibition activities of the aerial parts of Glaucium acutidentatum Hausskn. and Bornm. ...(family Papaveraceae). Methanolic and aqueous extracts were prepared by maceration, homogenizer-assisted extraction (HAE) and infusion. Results showed that the highest total phenolic and flavonoids contents were obtained from the methanol extracts obtained by HAE (53.22 ± 0.10 mg GAE/g) and maceration (30.28 ± 0.51 mg RE/g), respectively. The aporphine, beznyltetrahydroisoquinoline, and protopine types of Glaucium alkaloids have been tentatively identified. Among them, glaucine was identified in all extracts. Flavonoids, phenolic acids, coumarins, organic acids and fatty acids were also detected. Methanolic extract obtained using the HAE method displayed the highest anti-DPPH (41.42 ± 0.62 mg TE/g), total antioxidant (1.20 ± 0.17 mmol TE/g), Cu2+ (113.55 ± 6.44 mg TE/g), and Fe3+ (74.52 ± 4.74 mg TE/g) reducing properties. The aqueous extracts obtained by infusion and HAE methods exerted the best anti-ABTS (103.59 ± 1.49 mg TE/g) and chelating (19.81 ± 0.05 mg EDTAE/g) activities, respectively. Methanolic extract from HAE recorded the highest acetylcholinesterase (2.55 ± 0.10 mg GALAE/g) and α-amylase (0.51 ± 0.02 mmol ACAE/g) inhibition activities, while that obtained by maceration showed the best butyrylcholinesterase (3.76 ± 0.31 mg GALAE/g) inhibition activity. Both extracts revealed the best tyrosinase inhibitory activity (25.15 ± 1.00 and 26.79 ± 2.36 mg KAE/g, p ≥ 0.05). G. acutidentatum maceration-derived aqueous extract showed selective anticancer activity against cells originating from human hypopharyngeal carcinoma. In conclusion, these findings indicated that G. acutidentatum is a promising source of alkaloids and phenolic compounds for variable pharmaceutical formulations.
In this study, the total phenolic and flavonoid contents, HPLC‐DAD detected phytochemicals, antioxidant and enzyme inhibitory potential of methanolic and aqueous (as infusion) extracts of the ...medicinal plant, Anthocleista djalonensis (leaf and stem bark) collected from two locations, Mafiblé and Prikro, in Ivory Coast, were investigated. The ranges of total phenolic and flavonoid contents obtained were 14.17–46.95 mg gallic acid equivalent (GAE)/g and 2.96–34.76 mg rutin equivalent (RE)/g, respectively. Antioxidant abilities in terms of radical scavenging, reducing and metal chelating activity of the extracts in different assays were as follows: DPPH (4.90–48.82 mg trolox equivalent TE/g), ABTS (21.05–81.89 mg TE/g), CUPRAC (29.54–122.33 mg TE/g), FRAP (17.53–94.06 mg TE/g) and metal chelating (10.09–28.49 mg EDTAE/g. The extracts of A. djalonensis collected from Mafiblé, especially those of stem bark, contained higher level of total bioactive contents compared to Prikro extracts, detected by high‐performance liquid chromatography with photodiode‐array detection (HPLC‐DAD). Only the methanolic extracts irrespective of plant parts/location, showed inhibition against acetylcholinesterase (1.42–2.12 mg galantamine equivalent (GALAE)/g), while only the stem bark methanolic extract of A. djalonensis from Mafiblé was found to inhibit butyrylcholinesterase (0.65 mg GALAE/g). Thus, findings from this study could be useful for better application of the medicinal benefits from this plant.
The chemical compounds strongly correlated with biological activities for the tested extracts.
is a medicinal plant traditionally used for treating intestinal worms. In the present study, the chemical composition and bio-pharmacological properties of
extracts were investigated. Enzyme ...inhibition and scavenging/reducing properties of water, methanol, and ethyl acetate extracts were assayed. The extracts were also studied in an ex vivo experimental model of colon inflammation, and in this context the gene expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) were assayed. Additionally, in colon cancer HCT116 cells, the gene expression of transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), possibly involved in colon carcinogenesis, was conducted as well. The extracts showed a different qualitative and quantitative content of phytochemicals, with water and methanol extracts being richer in total phenols and flavonoids, among which are flavonol glycosides and hydroxycinnamic acids. This could explain, at least in part, the higher antioxidant effects shown by methanol and water extracts, compared with ethyl acetate extract. By contrast, the ethyl acetate was more effective as cytotoxic agent against colon cancer cells, and this could be related, albeit partially, to the content of thymol and to its putative ability to downregulate TRPM8 gene expression. Additionally, the ethyl acetate extract was effective in inhibiting the gene expression of COX-2 and TNFα in isolated colon tissue exposed to LPS. Overall, the present results support future studies for investigating protective effects against gut inflammatory diseases.
Species belonging to the Zingiberaceae family are of high nutritional, industrial, and medicinal values. In this study, we investigated the effect of processing steps (fresh vs. dried milled ...rhizomes) and extraction methodologies (hydrodistillation vs. hexane extraction) of curcuma essential oil on its chemical content (using GC-MS analysis), its antioxidant behavior (using in vitro assays such as DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation), and its enzyme inhibitory activities (on tyrosinase, acetylcholinesterase, butylcholinesterase, α-amylase, and α-glucosidase) supported by multivariate analysis, in silico studies, and molecular dynamics. The GC-MS investigations revealed a high degree of similarity in the chemical profile of fresh hydrodistilled and hexane-extracted essential oils with tumerone and curlone being the major metabolites. The extraction techniques affected the concentrations of other minor constituents such as terpinolene, caryophylla-4(12), 8(13)-dien-5α-ol, and neo-intermedeol, which were almost exclusively detected in the hydrodistilled fresh essential oil; however, zingiberene and β-sesquiphellandrene were predominant in the hexane-extracted fresh essential oil. In the dried curcuma rhizomes, tumerone and curlone contents were significantly reduced, with the former being detected only in the hydrodistilled essential oil while the latter was doubly concentrated in the hexane-derived oil. Constituents such as D-limonene and caryophyllene oxide represented ca. 29% of the dried hydrodistilled essential oil, while ar-turmerone was detected only in the dried hydrodistilled and hexane-extracted essential oils, representing ca. 16% and 26% of the essential oil composition, respectively. These variations in the essential oil chemical content have subsequently affected its antioxidant properties and enzyme inhibitory activities. In silico investigations showed that hydrophobic interactions and hydrogen bonding were the characteristic binding modes of the bioactive metabolites to their respective targets. Molecular dynamics revealed the stability of the ligand-target complex over time. From the current study we conclude that fresh hexane-extracted essential oil showed the best radical scavenging properties, and fresh rhizomes in general display better enzyme inhibitory activity regardless of the extraction technique.
