Browsing by Author "Yildiztugay, Evren"

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Citation - WoS: 28
Citation - Scopus: 28
Differential Metabolomic Fingerprinting of the Crude Extracts of Three Asteraceae Species With Assessment of Their in Vitro Antioxidant and Enzyme-Inhibitory Activities Supported by in Silico Investigations
(Mdpi, 2022) Zengin, Gokhan; Fahmy, Nouran M.; Sinan, Kouadio Ibrahime; Uba, Abdullahi Ibrahim; Bouyahya, Abdelhakim; Lorenzo, Jose M.; Yildiztugay, Evren; Fayez, Shaimaa
The Asteraceae is a large family, rich in ornamental, economical, and medicinally valuable plants. The current study involves the analytical and pharmacological assessment of the methanolic extracts of three less investigated Asteraceae plants, namely Echinops ritro, Centaurea deflexa, and Tripleurospermum decipiens, obtained by three different extraction methodologies viz. maceration (MAC), ultrasound-assisted extraction (UAE), and homogenizer-assisted extraction (HAE). LC-MS-MS analysis of E. ritro, C. deflexa, and T. decipiens extracts led to the identification of ca. 29, 20, and 33 metabolites, respectively, belonging to flavonoids, phenolic acids, and fatty acids/amides. Although there were significant differences in the quantitative metabolite profiles in the extracts of E. ritro and T. decipiens based on the used extraction method, no significant variation was observed in the extracts of C. deflexa in the three implemented extraction techniques. The antioxidant activities of the nine extracts were assessed in vitro using six different assays viz. DPPH, ABTS, CUPRAC, FRAP, PDA, and metal chelation assay (MCA). The HAE/UAE extracts of E. ritro and the UAE/ MAC extracts of C. deflexa displayed the highest antioxidant activity in the DPPH assay, while the UAE extract of T. decipiens showed the strongest antioxidant activity in both the CUPRAC and MCA assays. The enzyme inhibitory activities of the nine extracts were studied in vitro on five different enzymes viz. tyrosinase, alpha-amylase, alpha-glucosidase, acetylcholinesterase (AChE), and butyrylcholinestrase (BChE), affecting various pathological diseases. Concerning C. deflexa, its MAC /UAE extracts showed the strongest inhibition on alpha-amylase, while its UAE/HAE extracts displayed strong inhibitory power on AChE. However, no significant difference was observed on their effects on tyrosinase or BChE. For T. decipiens, its UAE/HAE showed potent inhibition to alpha-glucosidase, MAC/ HAE significantly inhibited AChE and BChE, while UAE could strongly inhibit tyrosinase enzyme. For E. ritro, all extracts equally inhibited alpha-amylase and alpha-glucosidase, MAC/HAE strongly affected tyrosinase, HAE/MAC best inhibited BChE, while HAE inhibited AChE to a greater extent. Chemometric analysis using PCA plot was able to discriminate between the plant samples and between the implemented extraction modes. The in vitro enzyme inhibitory activities of the extracts were supported by in silico data, where metabolites, such as the lignan arctiin and the flavonoid vicenin-2, dominating the extract of C. deflexa, displayed strong binding to AChE. Similarly, chlorogenic and dicaffeoyl quinic acids, which are some of the major metabolites in the extracts of E. ritro and T. decipiens, bound with high affinity to alpha-glucosidase.
Citation - WoS: 16
Citation - Scopus: 18
An In-Depth Study on the Metabolite Profile and Biological Properties of Primula auriculata Extracts: A Fascinating Sparkle on the Way from Nature to Functional Applications
(Mdpi, 2022) Kurt-Celep, Inci; Zheleva-Dimitrova, Dimitrina; Gevrenova, Reneta; Uba, Abdullahi Ibrahim; Zengin, Gokhan; Yildiztugay, Evren; Picot-Allain, Carene Marie Nancy; Montesano, Domenico
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-kappa B, 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 alpha-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.
Citation - WoS: 24
Citation - Scopus: 27
Integration of in Vitro and in Silico Approaches To Assess Three Astragalus Species From Turkey Flora: a Novel Spotlight From Lab Bench To Functional Applications
(Elsevier, 2022) Zengin, Gokhan; Uba, Abdullahi Ibrahim; Ocal, Mustafa; Sharifi-Rad, Majid; Caprioli, Giovanni; Angeloni, Simone; Altunoglu, Yasemin Celik; Yildiztugay, Evren
Members of the genus Astragalus have a great interest as a source of natural bioactive compounds on a scientific platform. To provide multidirectional insights into three Astragalus species (A. setulosus, A. anthylloides, and A. ovalis), the current work focused on the chemical characterization and biological properties of their extracts (aerial parts and roots). The chemical characterization of the extracts was detected by HPLC-MS/MS analysis. The biological properties were evaluated by antioxidant, enzyme inhibitory, and cytotoxic parameters. Assays for radical quenching, reducing capacity, and metal chelation were also used to evaluate antioxidant properties. To test the enzyme inhibitory effects of the extracts, cholinesterases, tyrosinase, alpha-amylase, and alpha-glucosidase were utilized as target enzymes. Two cancer cell lines, (MCF-7 (human breast cancer cell line) and HeLa (Human cervix cancer cell line), were selected to evaluate cytotoxic effects. Generally, 5- caffeoylquinic acid (2.43-283.92 mu g/g extract), hyperoside (4.33-216.22 mu g/g extract) and rutin (1.09-184.98 mu g/g extract) were the main constituents. The extracts from aerial parts and roots of A. anthylloides showed stronger radical scavenging and reducing power abilities compared to A. setulosus and A. ovalis. The best AChE and BChE inhibitory effects were determined in the aerial parts of A. setulosus (2.18 mg GALAE/g) and mots of A. ovalis (4.76 mg GALAE/g), respectively. The extracts of A. ovalis had the highest tyrosinase inhibitory abilities. The extract from aerial parts of A. setulosus showed stronger cytotoxic effects compared to other extracts. Pearson's correlation analysis revealed that the presence of some compounds (resveratrol, p-coumaric, 5-caffeoylquinic, and ferulic acids, etc) was linked to the observed biological activities. Molecular docking was also provided for the possible interaction of enzymes as well as protein targets of the tested cell lines. Our findings provide a scientific basis for the Astragalus species, which may serve as a source of naturally occurring bioactive compounds for health-promoting applications.