In this study, the inhibitory potential of bacterial neuraminidase (NA) was observed on the leaves of
Nakai, which is a popular ingredient in traditional herbal medicine. This study attempted to ...isolate the relevant, responsible metabolites and elucidate their inhibition mechanism. The methanol extraction process yielded eight flavonoids (
⁻
), of which compounds
and
were new compounds named koreanoside F and koreanoside G, respectively. All the compounds (
⁻
) showed a significant inhibition to bacterial NA with IC
values of 0.17⁻106.3 µM. In particular, the prenyl group on the flavonoids played a critical role in bacterial NA inhibition. Epimedokoreanin B (compound
, IC
= 0.17 µM) with two prenyl groups on C8 and C5' of luteolin was 500 times more effective than luteolin (IC
= 85.6 µM). A similar trend was observed on compound
(IC
= 0.68 µM) versus dihydrokaempferol (IC
= 500.4 µM) and compound
(IC
= 12.6 µM) versus apigenin (IC
= 107.5 µM). Kinetic parameters (
,
, and
/
) evaluated that all the compounds apart from compound
showed noncompetitive inhibition. Compound
was proven to be a mixed type inhibitor. In an enzyme binding affinity experiment using fluorescence, affinity constants (
) were tightly related to inhibitory activities.
The flora of Kazakhstan is characterized by its wide variety of different types of medicinal plants, many of which can be used on an industrial scale. The Traditional Kazakh Medicine (TKM) was ...developed during centuries based on the six elements of ancient Kazakh theory, associating different fields such as pharmacology, anatomy, pathology, immunology and food nursing as well as disease prevention. The endemic Artemisia L. species are potential sources of unique and new natural products and new chemical structures, displaying diverse bioactivities and leading to the development of safe and effective phytomedicines against prevailing diseases in Kazakhstan and the Central Asia region. This review provides an overview of Artemisia species from Central Asia, particularly traditional uses in folk medicine and the recent numerous phytochemical and pharmacological studies. The review is done by the methods of literature searches in well-known scientific websites (Scifinder and Pubmed) and data collection in university libraries. Furthermore, our aim is to search for promising and potentially active Artemisia species candidates, encouraging us to analyze Protein Tyrosine Phosphatase 1B (PTP1B), α-glucosidase and bacterial neuraminidase (BNA) inhibition as well as the antioxidant potentials of Artemisia plant extracts, in which endemic species have not been explored for their secondary metabolites and biological activities so far. The main result of the study was that, for the first time, the species Artemisia scopiformis Ledeb. Artemisia albicerata Krasch., Artemisia transiliensis Poljakov, Artemisia schrenkiana Ledeb., Artemisia nitrosa Weber and Artemisia albida Willd. ex Ledeb. due to their special metabolites, showed a high potential for α-glucosidase, PTP1B and BNA inhibition, which is associated with diabetes, obesity and bacterial infections. In addition, we revealed that the methanol extracts of Artemisia were a potent source of polyphenolic compounds. The total polyphenolic contents of Artemisia extracts were correlated with antioxidant potential and varied according to plant origin, the solvent of extraction and the analytical method used. Consequently, oxidative stress caused by reactive oxygen species (ROS) may be managed by the dietary intake of current Artemisia species. The antioxidant potentials of the species A. schrenkiana, A. scopaeformis, A. transiliensis and Artemisia scoparia Waldst. & Kitam. were also promising. In conclusion, the examination of details between different Artemisia species in our research has shown that plant materials are good as an antioxidant and eznyme inhibitory functional natural source.
Exposure to reactive oxygen species (ROS) leads to the oxidation of low-density lipoproteins (LDL), converting them into oxidized ones (oxLDL), which are involved in the pathogenesis of Alzheimer's ...disease, suggesting a potential link between lipid dysregulation and neurodegenerative processes. Phenolic metabolites derived from Artocarpus elasticus root bark were found to possess significant antioxidant properties at three different radical scavenging assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC), and thiobarbituric acid reactive substances (TBARS). Among them, furanodihydrobenzoxanthones (1-3) demonstrated notable protection against Cu2+ induced LDL oxidation, with IC50 values ranging from 0.9 to 2.9 μM in measurement of the malondialdehyde (MDA) production at TBARS and prolonged lag times (>180 min) in the generation of conjugated diene (CD). At a concentration of 10 μM, all three compounds (1-3) effectively protected against LDL oxidation as determined by relative electrophoretic mobility (REM). The most potent compound 1 defended human neuroblastoma SH-SY5Y cells from oxLDL-mediated dysfunction, including oxLDL-induced cytotoxicity, inhibited reactive oxygen species (ROS) formation, and enhancing mitochondrial membrane potential (ΔΨm). Individual components annotation in the ethylacetate extract was performed using LC-ESI-QTOF/MS, which serves as a chemotaxonomic marker for A. elasticus root barks.
•Artocarpus elasticus root bark metabolites possess strong antioxidant properties against radicals in various assays.•Furanodihydrobenzoxanthones from A. elasticus root bark protect against Cu2+-induced LDL oxidation.•Artonin W effectively defends SH-SY5Y cells from oxLDL-induced dysfunction and ROS formation.•LC-ESI-TOF/MS identified individual components in ethylacetate extract of A. elasticus root bark.
The aim of this study is to explore anti-inflammatory phytochemicals from
based on the inhibition of pro-inflammatory enzyme, human neutrophil elastase (HNE) and anti-inflammatory activities in ...lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage. Three stereoisomers of iridal-type triterpenoids (
-
) were isolated from the roots of
and their stereochemistries were completely identified by NOESY spectra. These compounds were confirmed as reversible noncompetitive inhibitors against HNE with IC
values of 6.8-27.0 µM. The binding affinity experiment proved that iridal-type triterpenoids had only a single binding site to the HNE enzyme. Among them, isoiridogermanal (
) and iridobelamal A (
) displayed significant anti-inflammatory effects by suppressing the expressions of pro-inflammatory cytokines, such as iNOS, IL-1β, and TNF-α through the NF-κB pathway in LPS-stimulated RAW264.7 cells. This is the first report that iridal-type triterpenoids are considered responsible phytochemicals for anti-inflammatory effects of
.
Xanthine oxidase is a frontier enzyme to produce oxidants, which leads to inflammation in the blood. Prenylated isoflavones from
were found to display potent inhibition against xanthine oxidase (XO). ...All isolates (
-
) inhibited XO enzyme with IC
ranging 7.8~36.4 μM. The most active isoflavones (
-
, IC
= 7.8~14.8 μM) have the structural feature of a catechol motif in B-ring. Inhibitory behaviors were disclosed as a mixed type I mode of inhibition with
<
. Binding affinities to XO enzyme were evaluated. Fluorescence quenching effects agreed with inhibitory potencies (IC
s). The compounds (
-
) also showed potent anti-LDL oxidation effects in the thiobarbituric acid-reactive substances (TBARS) assay, the lag time of conjugated diene formation, relative electrophoretic mobility (REM), and fragmentation of apoB-100 on copper-mediated LDL oxidation. The compound
protected LDL oxidation with 0.7 μM in TBARS assay, which was 40-fold more active than genistein (IC
= 30.4 μM).
Bacterial neuraminidase (BNA) plays a pivotal role in the pathogenesis of several microbial diseases including biofilm formation. The aim of this study is to reveal the neuraminidase inhibitory ...potential of metabolites from
(L.) Hook. which have diverse biological activities including PTP1B and
-glucosidase. The six ugonins (
) from the target plant showed significant neuraminidase inhibition. The inhibitory potencies were observed at a nanomolar level of 35-50 nM, which means they are 100 times more active than their corresponding mother compounds (eriodyctiol and luteolin). A detailed kinetic study revealed that all ugonins were reversible noncompetitive inhibitors. An in-depth investigation of the most potent compound
showed its time-dependent inhibition with the isomerization model having
= 0.0103 min
,
= 0.0486 min
, and
= 0.062 μM. The binding affinities (
) were agreed closely with our prediction based on the inhibitory potencies. Particularly, ugonin J (
) blocked the biofilm formation of
dose-dependently up to 150 µM without the inhibition of bacteria. The major compounds (
) in the extract were characterized by UPLC-ESI-Q-TOF/MS.
Abundance of metabolites in plant is a critical factor toward being functional food stuff. Salicylic acid (SA) treatment led significant changes in levels of the secondary metabolites in soybean ...roots. Notably, the exposure of 3 mM of SA aqueous solution to soybean plants for 24 h resulted in distinctive increases in the levels of coumestrol (16-fold, 0.3–4.8 mg/g DW) and daidzein (7-fold, 1.2–8.9 mg/g DW) in roots part. These changes were systematically investigated by LC-ESI-TOF/MS analysis to afford a clear difference of PLS-DA score, heatmap, and box plots. Quantitative analysis showed that SA treatment played to stimulate biosynthesis of coumestrol as well as hydrolysis of its glycosides (coumestrin and malonylcoumestrin). The highly improved anti-LDL oxidation effect was observed in the SA treated soybean roots in the three different assay systems. It might be rationalized by the increased levels of coumestrol and daidzein.
Protein tyrosine phosphatase 1B (PTP1B) is one of the target enzymes whose disruption leads to obesity and diabetes. A series of PTP1B inhibitors were isolated from the leaves of Artocarpus ...elasticus, used in traditional medicines for diabetes. The isolated inhibitors (1–13), including two new compounds (1 and 2), consisted of dihydroflavonols and flavones. The structural requirements for the PTP1B inhibitory mode and potency were revealed in both skeletons. The two highest PTP1B inhibitory properties were dihydroflavonol 1 and flavone 6 analogs with IC50 values of 0.17 and 0.79 μM, respectively. The stereochemistry also affected inhibitory potencies: trans isomer 1 (IC50= 0.17 μM) vs cis isomer 2 (IC50= 2.24 μM). Surprisingly, the dihydroflavonol and flavone glycosides (11 and 13) displayed potent inhibition with IC50s of 2.39 and 0.22 μM, respectively. Furthermore, competitive inhibitor 1 was applied to time-dependence experiments as a simple slow-binding inhibitor with parameters of K i app = 0.064103 μM, k 3 = 0.2262 μM–1 min–1, and k 4 = 0.0145 min–1. The binding affinities by using the fluorescence quenching experiment were highly correlated with inhibitory potencies: 1 (IC50= 0.17 μM, K SV = 0.4375 × 105 L·mol–1) vs 3 (IC50= 17.79 μM, K SV = 0.0006 × 105 L·mol–1). The specific binding interactions were estimated at active and allosteric sites according to the inhibitory mode by molecular docking.
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•Quercetin derivatives (1-13) including the new (2) were isolated from M. glabra.•O-Alkylated quercetins were selective inhibitory potential toward hAChE and BACE1.•All compounds from ...M. glabra had a significant antioxidant potentials.•LC-ESI-Q-TOF/MS disclosed inhibitors as main metabolite of M. glabra leave extract.
Intensive investigation of phytochemicals from edible Melicope glabra leaves provided a series of O-alkylated quercetins (1–13). The quercetin 1 bearing prenyl and methyl motif showed potent inhibition to human acetylcholinesterase (hAChE) with mixed type I mode, while quercetin was inactive. The position of methyl group was also a critical factor to hAChE inhibition: 1 (4′-O-methyl, IC50 = 12.7 μM) vs2 (3′-O-methyl, IC50 = 119 μM). Inhibitory potency was doubly confirmed with the binding affinity (KSV) based on fluorescence quenching. O-Methyl groups on quercetin were observed to influence β-secretase (BACE1) inhibition. Thus, O-methylated quercetins (4–6) displayed potential inhibitions against BACE1 with IC50 values of 1.3, 4.1, and 14.1 μM, respectively. All compounds (3–6) have noncompetitive mode to BACE1. Additionally, all quercetin derivatives (1–13) had antioxidant potentials against different radical sources (ABTS, ORAC and FRAP). The UPLC-ESI-Q-TOF/MS indicated that the leaves part had promising metabolites towards hAChE and BACE1 inhibitions, which are the most predominant phytochemicals.
In this study, the changes in free amino acids of soybean leaves after ethylene application were characterized based on quantitative and metabolomic analyses. All essential and nonessential amino ...acids in soybean leaves were enhanced by fivefold (250 to 1284 mg/100 g) and sixfold (544 to 3478 mg/100 g), respectively, via ethylene application. In particular, it was found that asparagine is the main component, comprising approximately 41% of the total amino acids with a twenty-five fold increase (78 to 1971 mg/100 g). Moreover, arginine and branched chain amino acids (Val, Leu, and Ile) increased by about 14 and 2-5 times, respectively. The increase in free amino acid in stem was also similar to the leaves. The metabolites in treated and untreated soybean leaves were systematically identified by gas chromatography-mass spectrometry (GC-MS), and partial variance discriminant analysis (PLS-DA) scores and heat map analysis were given to understand the changes of each metabolite. The application of ethylene may provide good nutrient potential for soybean leaves.
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