Showing papers on "Acacetin published in 2019"
TL;DR: The findings presented in this work suggest that the Caucasian gentians are a good source of bioactive phytocompounds with antioxidant and antidiabetic potential.
Abstract: The members of Gentiana genus are widely distributed in the Caucasus region where they are used as phytoremedies, but they still have not been studied for their chemical composition and bioactivity. High-performance liquid chromatography with diode array and electrospray triple quadrupole mass detection (HPLC-DAD-ESI-QQQ-MS) was used to investigate metabolites of herb and roots of six gentians (Gentiana asclepiadea, G. cruciata, G. gelida, G. paradoxa, G. pneumonanthe, G. septemfida) grown in the Caucasus. In total, 137 compounds were found including three carbohydrates, 71 iridoid glycosides (mostly loganic acid), loganin, swertiamarin, gentiopicroside and sweroside derivatives, 40 flavones C-, O-, C,O-glycosides (such as luteolin, apigenin, chrysoeriol, and acacetin derivatives), two phenolic O-glycosides, five hydroxycinnamates, eight xanthones, and seven triterpene glycosides. Most of these compounds were identified in gentian samples for the first time. Quantitative differences were found in levels of seven iridoid glycosides, nine glycosylflavones, and two xanthones obtained by HPLC-DAD assay. The gentian extracts were evaluated for their radical-scavenging properties against DPPH and superoxide anion radicals, lipid peroxidation inhibition, and α-amylase/α-glycosidase inhibition. The herb extracts showed higher activity than root extracts. Positive correlations were found between the content of quantified phenolics and antioxidant and digestive enzymes inhibiting activity. The findings presented in our work suggest that the Caucasian gentians are a good source of bioactive phytocompounds with antioxidant and antidiabetic potential.
42 citations
TL;DR: The findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.
38 citations
TL;DR: The investigation of the constituents that were isolated from Turnera diffusa for their inhibitory activities against recombinant human monoamine oxidases in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B, suggesting further investigations on acacet in 7- methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson's disease.
Abstract: The investigation of the constituents that were isolated from Turnera diffusa (damiana) for their inhibitory activities against recombinant human monoamine oxidases (MAO-A and MAO-B) in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B (IC50 = 198 nM). Acacetin 7-methyl ether (also known as 5-hydroxy-4′, 7-dimethoxyflavone) is a naturally occurring flavone that is present in many plants and vegetables. Acacetin 7-methyl ether was four-fold less potent as an inhibitor of MAO-B when compared to acacetin (IC50 = 50 nM). However, acacetin 7-methyl ether was >500-fold selective against MAO-B over MAO-A as compared to only two-fold selectivity shown by acacetin. Even though the IC50 for inhibition of MAO-B by acacetin 7-methyl ether was ~four-fold higher than that of the standard drug deprenyl (i.e., SelegilineTM or ZelaparTM, a selective MAO-B inhibitor), acacetin 7-methyl ether’s selectivity for MAO-B over MAO-A inhibition was greater than that of deprenyl (>500- vs. 450-fold). The binding of acacetin 7-methyl ether to MAO-B was reversible and time-independent, as revealed by enzyme-inhibitor complex equilibrium dialysis assays. The investigation on the enzyme inhibition-kinetics analysis with varying concentrations of acacetin 7-methyl ether and the substrate (kynuramine) suggested a competitive mechanism of inhibition of MAO-B by acacetin 7-methyl ether with Ki value of 45 nM. The docking scores and binding-free energies of acacetin 7-methyl ether to the X-ray crystal structures of MAO-A and MAO-B confirmed the selectivity of binding of this molecule to MAO-B over MAO-A. In addition, molecular dynamics results also revealed that acacetin 7-methyl ether formed a stable and strong complex with MAO-B. The selective inhibition of MAO-B suggests further investigations on acacetin 7-methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson’s disease.
36 citations
TL;DR: Detailed structure-inhibition relationships of flavonoid-type UGT1A1 inhibitors were investigated carefully and the findings shed new light on the interactions between flavonoids and UGT 1A1, and will contribute considerably to the development of flavonside-type drugs without strong UGT2A1 inhibition.
33 citations
TL;DR: This study is the first to characterize ac acetin metabolites in vivo and in vitro, and the results offer novel and valuable evidence for a comprehensive understanding of the safety and efficacy of acacetin.
Abstract: Acacetin, a dietary component, is abundant in acacia honey and has superior anticancer activities. To date, no research on the metabolism of acacetin has been reported. In the current research, an online detection strategy of ultra-high-performance liquid chromatography connected to a quadrupole time-of-flight mass spectrometer (UHPLC-Q-TOF-MS/MS) was utilized for metabolite identification in vivo (rat plasma, bile, urine, and feces) and in vitro (rat liver microsomes). A total of 31 metabolites were structurally characterized in rats, and 25 metabolites were detected in rat liver microsomes, among which, 4 metabolites were compared with standards. Oxidation, the loss of CH2, reduction, hydrolysis, glucuronide conjugation, sulfate conjugation, methylation, and N-acetylation were the main metabolic pathways of acacetin. This study is the first to characterize acacetin metabolites in vivo and in vitro, and the results of this study offer novel and valuable evidence for a comprehensive understanding of the safety and efficacy of acacetin.
31 citations
TL;DR: It is concluded that isoginkgetin had higher electron transfer potential than its monomer because of the 3′,8″-dimerization and can produce a dimer during its antioxidant process; however, the dimer is not isogin.
Abstract: To probe the effect of 3′,8″-dimerization on antioxidant flavonoids, acacetin and its 3′,8″-dimer isoginkgetin were comparatively analyzed using three antioxidant assays, namely, the ·O2− scavenging assay, the Cu2+ reducing assay, and the 2,2′-azino bis(3-ethylbenzothiazolin-6-sulfonic acid) radical scavenging assay. In these assays, acacetin had consistently higher IC50 values than isoginkgetin. Subsequently, the acacetin was incubated with 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxy radicals (4-methoxy-TEMPO) and then analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC−ESI−Q−TOF−MS) technology. The results of the UHPLC−ESI−Q−TOF−MS analysis suggested the presence of a dimer with m/z 565, 550, 413, 389, 374, 345, 330, and 283 peaks. By comparison, standard isoginkgetin yielded peaks at m/z 565, 533, 518, 489, 401, 389, 374, and 151 in the mass spectra. Based on these experimental data, MS interpretation, and the relevant literature, we concluded that isoginkgetin had higher electron transfer potential than its monomer because of the 3′,8″-dimerization. Additionally, acacetin can produce a dimer during its antioxidant process; however, the dimer is not isoginkgetin.
28 citations
TL;DR: Evaluating the antimicrobial and anti-diabetic potential of different extracts and isolated flavone C- glycoside compounds from Beta vulgaris subspecies cicla L. flavescens found it to be a potential candidate for the treatment of several health disorders associated with infectious diseases and diabetes.
Abstract: Background Diabetes mellitus is the most common disease in Egypt. In this context, Beta vulgaris subspecies cicla L. var. flavescens is an edible plant that has been used in traditional medicine as a therapy for treating some diseases. Objectives The current study was performed to evaluate the antibacterial and potential anti-diabetic activities of different extracts and isolated flavone C-glycoside compounds isolated from Beta vulgaris subspecies cicla L. var. flavescens leaves. Methods Phytochemical investigation of n-butanol extract led to the isolation of five phytoconstituents. Their structures were determined by spectroscopic tools, including 1D-NMR (1H- & 13C-NMR) and 2D-NMR (HMQC & HMBC) besides the comparison of the data with the literature. The extracts and phytoconstituents were evaluated in vitro for their activity against some bacterial pathogens, which represent prominent human pathogens, particularly in hospital settings. The antibacterial activity was examined against three Gram-positive bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis & Enterococcus faecalis) and five Gram-negative ones (Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae, Proteus mirabilis & Salmonella typhimurium) relative to Ciprofloxacin as a reference drug. Furthermore, the in vitro antidiabetic activity (Type II) was evaluated using the alpha-glucosidase inhibitory assay. Results Five flavone C-glycosides namely; Apigenin 8-C-β-D-glucopyranoside (vitexin) (1), 2''-Oxylopyranosylvitexin (2), acacetin 8-C-β-D-glucopyranoside (3), acacetin 8-C-α-L-rhamnoside (4), and 6,8-di-C-β-D-glucopyranosylapigenin (vecinin-II) (5) were isolated from n-butanol extract of B. vulgaris subspecies cicla L. var. flavescens. Compound 1 showed a promising antibacterial activity against most of the test bacterial strains with respect to the minimum inhibitory concentration values (MIC) ranged from 1.95 to 15.63 µg ml-1. On the other hand, compounds 1 and 3 demonstrated superior antidiabetic activities with IC50 values of 35.7 and 42.64 µg ml-1, respectively, while an inferior potential antidiabetic activity was recorded for compound 4 (IC50 = 145.5 µg ml-1) in comparison with Acarbose as a reference drug. Conclusion B. vulgaris L. is an edible plant, which could be used as a natural source of antibiotic and hypoglycemic drugs.
27 citations
TL;DR: The aim of this study was to determine the enzymatic kinetics of O-demethylation and aromatic hydroxylation of flavonoid aglycons on recombinant cytochrome P450 enzymes and human liver microsomes systems and to consider the potential of drug-flavonoid competitive interactions/inhibitions.
Abstract: One of the most important groups of metabolic enzymes is cytochrome P450 superfamily. These enzymes are important in terms of the catalytic diversity and the large number of xenobiotics that are detoxified or activated by converting to reactive metabolites. Flavonoids are xenobiotics to which humans are exposed through diet. Data on their oxidative metabolism mediated by cytochromes P450 are limited. The aim of this study was to determine the enzymatic kinetics of O-demethylation and aromatic hydroxylation of flavonoid aglycons on recombinant cytochrome P450 enzymes and human liver microsomes systems. The study was performed on ten flavonoids, namely 3,7-dihydroxyflavone, 7-hydroxyflavone, acacetin, apigenin, flavone, galangin, kaempferol, naringenin, sakuranetin, and tangeretin using liquid chromatography coupled with mass spectrometry and UV detector. Most relevant enzyme involved in metabolism of flavonoid aglycons is CYP1A2, and its catalytic effectiveness ranges from 0.5 to 2.9 × 106 M–1 min–1. Having in mind high expression and involvement of CYP1A2 in metabolism of xenobiotics including drugs, and its intraindividual differences in expression and activity, potential of drug-flavonoid competitive interactions/inhibitions should be considered when consuming dietary supplement and foods rich in flavonoids.
This work is licensed under a Creative Commons Attribution 4.0 International License .
27 citations
TL;DR: A comprehensive overview of the potential therapeutic applications of acacetin was prepared after collating selected peer-reviewed papers, accessed from online scientific databases, specifically PubMed, Web of Science and Scopus.
26 citations
TL;DR: Insight is provided into the potential application of molecular breeding and metabolic engineering for improving the quality of cultivated C. indicum and a linarin biosynthesis pathway is proposed.
24 citations
TL;DR: It is confirmed that chronic acatetin administration to mice engenders antidepressant-like efficacy on both behavior and stress axis responsivity, with serotonergic system that preferentially couples with 5-HT1A receptors being critically involved.
TL;DR: Results coupled with simulation studies modeling flavonoid interaction within the AhR binding pocket demonstrate that the orientation of the substituted phenyl ring at C-2 (flavones) or C-3 (is oflavones) on the common 4-H-chromene-4-one ring strongly influences the activities of isoflavones and flavones as AhR agonists.
Abstract: Many of the protective responses observed for flavonoids in the gastrointestinal track resemble aryl hydrocarbon receptor (AhR)-mediated effects. Therefore, we examined the structure-activity relationships of isoflavones and isomeric flavone and flavanones as AhR ligands on the basis of their induction of CYP1A1, CYP1B1, and UGT1A1 gene expression in colon cancer Caco2 cells and young adult mouse colonocyte (YAMC) cells. Caco2 cells were significantly more Ah-responsive than YAMC cells, and this was due, in part, to flavonoid-induced cytotoxicity in the latter cell lines. The structure-activity relationships for the flavonoids were complex and both response and cell context specific; however, there was significant variability in the AhR activities of the isomeric substituted isoflavones and flavones. For example, 4',5,7-trihydroxyisoflavone (genistein) was AhR-inactive whereas 4',5,7-trihydroxyflavone (apigenin) induced CYP1A1, CYP1B1, and UGT1A1 in Caco2 cells. In contrast, both 5,7-dihydroxy-4-methoxy substituted isoflavone (biochanin A) and flavone (acacetin) induced all three AhR-responsive genes; 4',5,7-trimethoxyisoflavone was a potent AhR agonist, and the isomeric flavone was AhR-inactive. These results coupled with simulation studies modeling flavonoid interaction within the AhR binding pocket demonstrate that the orientation of the substituted phenyl ring at C-2 (flavones) or C-3 (isoflavones) on the common 4-H-chromen-4-one ring strongly influences the activities of isoflavones and flavones as AhR agonists.
TL;DR: Three acacetin triglycosides (compounds 1, 2 and 3) were isolated from the herbs of Elsholtzia ciliata (Labiatae) to find anti-Alzheimer’s activity, since this enzyme increases the concentration of acetylcholine (ACh), a neurotransmitter, responsible for brain's memory.
TL;DR: In this paper, the spatial distribution of key flavonoids in peppermint leaves was assessed using DESI-MSI images in the negative ion mode, and the results described in this paper were shown to be very interesting.
Abstract: Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to assess the spatial distribution of some key flavonoids in peppermint (Mentha × piperita L.) leaves. The chemical images were generated by applying DESI-MSI on the peppermint leaves imprinting while acquiring the spectra in the negative ion mode. The following key flavonoids were detected and grouped within well-known biosynthetic routes in plants: naringenin route [naringenin, sakuranetin, hesperetin, hesperidin, luteolin, and apigenin]; luteolin route [luteolin, chrysoeriol, luteolin-7-O-D-glucuronide, luteolin-7-O-D-glucoside, luteolin-7-O-neohesperidoside]; apigenin route [apigenin, apigenin-7-O-gentiobioside, apigenin-7-O-neohesperidoside, thymusin/pilosin, pebrellin, acacetin/genkwanin, ladanein, xanthomicrol/pedunculin/nevadensin]. Maps of the spatial distribution of these flavonoids throughout the peppermint leaves within each route were then displayed. The results described herein comprise an important (although still underexplored) subject that certainly will experience a remarkable growth in the next years.
TL;DR: An novel UHPLC-QTOF-MS/MS method combined with in silico approach was applied to identify the flavonoids and metabolites profiling in biological samples following oral administration of NHSQTs for the first time, finding 127 compounds including 34 original compounds of flavonoid and 93 metabolites.
TL;DR: Data indicate that acacetin‐induced cell apoptosis in HNSCC cells may be through M3R related calcium signaling and caspase 3 activation, which is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M 3R.
Abstract: Aacacetin, a plant flavone has shown antitumor efficacy recently. However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M3 R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell carcinoma (HNSCC) cells. Our results showed that 12.5- to 200-μM acacetin inhibited cell viability in dose- and time-dependent manners in HNSCC cells, but a relative higher concentration was needed for oral adenoid cystic carcinoma cells. M3 R expression level was higher in HNSCC cells than that in adenoid cystic carcinoma cells. Flow cytometry and electron microscopy confirmed acacetin-induced cell apoptosis in 22B cells, a HNSCC cell line. Acacetin promoted mitochondrial cytochrome c release and caspase 9, 3 processing. Knocking down of M3 R expression by specific siRNA significantly prevented the acacetin-induced cell viability damage, cell apoptosis, and caspase 3 activation. Besides, M3 R was also involved in acacetin-induced elevation of reactive oxygen species and intracellular calcium ([Ca2+ ]i ). These data indicate that acacetin-induced cell apoptosis in HNSCC cells may through M3 R related calcium signaling and caspase 3 activation. Acacetin is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M3 R.
27 Jun 2019
TL;DR: It is concluded that the PPs can reduce the destructive effect of UVR on the skin cells, activating the process of repairing genetic damage.
Abstract: The work investigated the responses of cultured human keratinocytes to ultraviolet radiation in the C range (UVC) with and without a number of plant polyphenolic compounds. The experimental data obtained in this work indicate a cytoprotective effect of the PPs added immediately after UVC exposure. The cytoprotective activity of plant polyphenolic compounds was reduced in the series: acacetin, silybin, baikalein, leontopodium acid, quercetin, cyanidine chloride, taxifolin, trans-ferulic acid. The effect of UVC irradiation with and without of acacetin on the process of phosphorylation of histones H2AX, the triggering mechanism for the repair of single-stranded DNA damage, was also investigated in keratinocytes. It has been established that, H2AX phosphorylation is activated in response to UVC radiation and acacetin has a significant effect on the kinetics of this process. It is concluded that the PPs can reduce the destructive effect of UVR on the skin cells, activating the process of repairing genetic damage.
TL;DR: It could be concluded that the acacetin possessed relatively greater bioavailability; thus this drug exhibited significant satisfactory pharmacokinetic profile which would be helpful for successful designing of a suitable dosage form formulation.
Abstract: Aim: The flavonoid compound (Acacetin) isolated from fruits of Gmelina arborea was investigated for its pharmacokinetic evaluation to find out the suitability of this compound to be formulated in any suitable dosage form. Method: The acacetin was administered intravenously and orally in Wistar rats at a dose of 2 and 10 mg/Kg body weight respectively. In a regular interval of specified time, blood samples were collected and bio-analyzed to quantify the drug concentration in the blood sample by using LC-MS. The Cmax, Tmax, T1/2, KE, Ka, and bioavailability (F) of acacetin were determined by mathematically and graphically from plasma concentration-time profile data. Absorption rate constant was determined by the method of residual. Results: From the i.v. Bolus administration data, acacetin had an area under curve (AUC) is 1.542 µg.h/ml, elimination rate constant (KE) is 0.423 h-1, and half-life (T1/2) is two hour. The oral administration of acacetin showed the peak plasma concentration (Cmax) of 1.668 µg/ml, Tmax is 1 h, AUC is 6.44 µg h/ml, KE is 0.416 h-1, T1/2 is 2 h, absorption rate constant (Ka) is 1.6 h and bioavailability of acacetin was found to be 84 %. Conclusion: From the study it could be concluded that the acacetin possessed relatively greater bioavailability; thus this drug exhibited significant satisfactory pharmacokinetic profile which would be helpful for successful designing of a suitable dosage form formulation.
TL;DR: Monkey may represent a suitable model for experimental studies of acacetin pharmacokinetics owing to a high sequence homology of UGT1A1 and similar UGT 1A1 glucuronidation activity to humans.
Patent•
02 Apr 2019
TL;DR: In this paper, a preparation method of acacetin was proposed, which solved the problems that a reagent for a conventional chemical synthesis is complex, high in toxicity, unfriendly to environment, severe inreaction condition, and unsuitable for large-scale industrial production.
Abstract: The invention provides a preparation method of acacetin, and solves the problems that a reagent for a conventional chemical synthesis is complex, high in toxicity, unfriendly to environment, severe inreaction condition, and unsuitable for large-scaled industrial production. The preparation method comprises the steps of selecting dihydro myricitrin as an initial raw material, and hydrolyzing the dihydro myricitrin under alkaline environment to obtain a hydroxyacetophenone intermediate; performing a catalyzing cyclization reaction on the hydroxyacetophenone and p-anisaldehyde to obtain a flavonol intermediate; and reducing the flavonol intermediate to obtain an acacetin crude product, and finally, performing refining to obtain acacetin quality products in which the content of a liquid phaseis 98% or above. The technology is low in cost, high in yield, simple in reaction condition, simple and safe to operate, economical and practical, environmental-friendly and pollution-free, the product quality meets market requirements, and the reagent is suitable for large-scale industrial production.
Patent•
13 Aug 2019
TL;DR: In this paper, a method for preparing an enzymatic extract of whole plant body of Viola mandshurica, and an anti-inflammatory functional cosmetic composition comprising the enzyme extract containing acacetin as an active ingredient.
Abstract: The present application relates to a method for preparing an enzymatic extract of whole plant body of Viola mandshurica, an enzymatic extract of whole plant body of Viola mandshurica prepared by the method, and an anti-inflammatory functional cosmetic composition comprising the enzymatic extract of whole plant body of Viola mandshurica containing acacetin as an active ingredient. The preparation method includes the steps of obtaining a concentrate; obtaining an enzyme additive; inactivating an enzyme; and obtaining an enzymatic extract of whole plant body of Viola mandshurica.
TL;DR: In this paper, a new flavonoid glycoside was isolated from Schizonepeta annua (Pall.) Schischk. by column chromatography, and its structure was determined to be acacetin 7-O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylopyraniumyl-( 1→6)]-β -D-glucopyranoide (1) by spectroscopic data.
Abstract: A new flavonoid glycoside 1 was isolated from Schizonepeta annua (Pall.) Schischk. by column chromatography. Its structure was determined to be acacetin 7-O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→6)]-β-D-glucopyranoside (1) by spectroscopic data (1H NMR, 13C NMR, 1H−1H COSY, HSQC, and HMBC) and chemical methods. In addition, the α-glucosidase inhibitory activity of compound 1 was evaluated.