Revealing the interaction mechanism of proteins with bioactive molecules and the location of their binding pockets is crucial for predicting the structure-function relationship of proteins in drug ...discovery and design. Despite some published papers on the interaction of β-casein with small bioactive molecules, the ambiguity of the location and constituent amino acids of β-casein binding pockets prompted us to identify them by in silico simulation of its interaction with three polyphenols, chrysin, apigenin, and luteolin. Molecular docking revealed that the primary β-casein binding pocket for chrysin consists of five nonpolar amino acids (Leu73, Phe77, Pro80, Ile89, and Pro196), three polar neutral amino acids (Ser137, Gln138, and Gln197), and two polar charged amino acids (Glu136, and Arg198). For β-casein/apigenin and β-casein/luteolin complexes, Asn83 also contributes to forming the pocket. Molecular dynamics provided more details, such as the relative contribution of determinative amino acids and the role of various forces. For example, we found that Glu210, Glu132, and Glu35 are the most destructive residues in the binding of chrysin, apigenin, and luteolin to β-casein, respectively. Also, we observed that hydrophobic forces mainly stabilize β-casein/chrysin and β-casein/apigenin, and polar solvation (including hydrogen bonds) stabilizes β-casein/luteolin, all by spontaneous processes.
•β-casein has multiple binding sites due to its structural flexibility and amphiphilicity.•The binding of β-casein to chrysin, apigenin, and luteolin is a spontaneous process with a decrease in stability as follows: β-casein/chrysin > β-casein/apigenin > β-casein/luteolin.•Hydrophobic interactions (for β-casein/chrysin and β-casein/apigenin) and polar solvation (for β-casein/luteolin) are the main stabilizing interactions.•More polar ligands, such as luteolin, induce more folding in the β-casein structure.•Glu210, Glu132, and Glu35 are the most destructive residues in the binding of chrysin, apigenin, and luteolin to β-casein, respectively.
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•C1-LNC and C5-LNC improvement neurobehavioral changes induced by β-amyloid1–42.•Chrysin loaded lipid-core nanocapsules attenuates neuroinflammation induced by Aβ1−42.•C1-LNC and ...C5-LNC modulate the redox status induced by β-amyloid1–42.
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by β-amyloid1–42 (Aβ1−42) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aβ1–42 administration (400 pmol, i.c.v.). Aβ1–42 induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aβ₁−₄2, via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.
Hormonal imbalances, particularly those involving estrogen and progesterone, are strongly associated with the development of breast cancer. Exemestane, an irreversible aromatase inhibitor, is used to ...treat estrogen-positive breast cancer. However, its clinical effectiveness is hampered by poor water solubility and bioavailability. Additionally, relying solely on a single chemotherapeutic agent often leads to poor therapeutic outcomes. Thus, there is a growing interest in the co-delivery of anticancer drugs, especially those of natural origin. In this study, our aim was to develop and optimize micelles for the simultaneous delivery of Exemestane and Chrysin. Exemestane was incorporated into mixed micelles via physical loading, while chrysin was linked to Pluronic L121 to create CHS-L121. Employing the Box-Benken design of experiments, we investigated the impact of polymer concentration on the independent variable. The optimized mixed micelles exhibited a particle size of 33.04 ± 2.62 nm and a polydispersity index of 0.145 ± 0.02. Notably, these micelles demonstrated excellent drug loading (5.2±2.2 %) and entrapment efficiency (89.6±2.5 %). In addition, CHS-EXE-MMs exhibited significant cytotoxicity against the MCF-7 cell line and showed enhanced in vivo anticancer activity in BALB/c mice. In vivo pharmacokinetic studies further revealed improved bioavailability of EXE and CHS through micelles. Our findings highlight the potential of CHS-EXE-MMs as a promising approach in breast cancer therapy.
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•Chrysin-L121 conjugated polymer was successfully designed.•Exemestane loaded mixed micelle successfully developed using chrysin-L121 conjugated polymer.•Box-Behnken design was used to optimize mixed micelles.•In vitro and in vivo investigations showed improved anticancer potential of EXE and CHS.
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Chrysin (5,7-dihydroxylflavone, Chry) is a natural flavonoid extracted from plants and propolis. In this work, a novel chrysin–organotin (Chry–Sn) compound with enhanced anticancer ...activities was synthesized by the reaction of chrysin and triphenyltin chloride, and its potential anticancer effects against cancer cells were measured using various methods. Sulforhodamine B (SRB) results showed that chrysin and Chry–Sn had significant inhibition effects on the proliferation of MCF-7, A549 and HeLa human cancer cell lines in a dose- and time- dependent manner. These results suggested that Chry–Sn possessed enhanced anticancer effects. Hoechst 33258 staining and acridine orange staining results showed apoptosis and nuclei fragments significantly increased after being treated with chrysin and Chry–Sn respectively. Moreover, chrysin and Chry–Sn significantly increased ROS levels in MCF-7 cells. Western blot results showed that chrysin and Chry–Sn activated caspase 3 and induced autophagy by increasing LC3-II level. All results showed collectively that Chry–Sn could be a more promising drug than chrysin in anticancer treatment.
•Anxiety-like behavior increases during metestrus-diestrus phase.•Chrysin reduces anxiety-like behavior associated with metestrus-diestrus phase.•Diazepam, but not chrysin, produces motor ...hypoactivity during proestrus-estrus phase.•Picrotoxin blocks anxiolytic-like effect of chrysin in cycling rats.
Low concentrations of ovarian hormones, among other factors, are associated with greater vulnerability to negative effects of environmental stressors and may trigger anxiety symptoms in females. The flavonoid chrysin (5,7-dihydroxyflavone) exerts anxiolytic-like effects in male and ovariectomized female rats, but it is unknown if chrysin could reduce anxiety-like behavior that naturally occurs through the ovarian cycle phases. The present study evaluated the effect of chrysin on anxiety-like behavior associated with the ovarian cycle phases in rats and the participation of γ-aminobutyric acid-A (GABAA) receptors in these actions. The acute effects of chrysin (2 mg/kg) were investigated in female cycling Wistar rats in the elevated plus maze, locomotor activity test, and light/dark test. Diazepam (2 mg/kg) was used as reference anxiolytic drug. The participation of GABAA receptor in the anxiolytic actions of chrysin was explored by pretreating the rats with the noncompetitive GABAA chloride ion channel antagonist picrotoxin (1 mg/kg). Chrysin and diazepam prevented anxiety-like behavior that was associated with the metestrus-diestrus phase in both the elevated plus maze and light/dark test, and these effects were reversed by picrotoxin, with no significant changes in spontaneous locomotor activity. No significant motor effects of chrysin were detected in either behavioral test during proestrus-estrus or metestrus-diestrus phases, whereas diazepam produced motor hypoactivity in the locomotor activity test during proestrus-estrus phase. These results indicate that the flavonoid chrysin prevents anxiety-like behavior that naturally occurs during metestrus-diestrus in two unconditioned models that are used to evaluate anxiety-like behavior, and these effects were mediated by actions on GABAA receptors.
Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in ...mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions.
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Chrysin (CHR), a dihydroxy flavone, exhibits several bioactivities,
, anti-oxidant, anti-inflammatory, and anti-cancer, and is known to possess limited aqueous solubility causing lowered ...bioavailability, and compromised therapeutic efficacy. Gold nanoparticles (AuNPs) conjugated chrysin (CHR–AuNPs) were prepared and characterized by UV-Vis, Fourier transform infra-red, X-ray diffraction, energy dispersive X-ray (EDX), and zeta potential analyses. The nanoformulated CHR–AuNPs were primarily examined on trial scale for their cytotoxic, anti-oxidant, and anti-microbial activity in comparison to the unformulated CHR. The CHR–AuNPs effectively scavenged the 2,2-diphenyl-1-picrylhydrazyl free radicals, also in comparison to CHR and AuNPs. The CHR–AuNPs also exhibited potential cytotoxic effects in a dose-dependent manner and demonstrated significant reduction (
0.05) of the cells proliferation, and growth of the human breast cancer cell lines, AMJ13, which were measured by 3-(4,5-dimethylthiazal-
-yl)-2,5-diphenyltetrazolium, and crystal violet assays, respectively. When compared with the pure CHR and free-AuNPs, the CHR–AuNPs exerted highest anti-microbial bioactivity against
and
. The strong anti-oxidant, anti-microbial, as well as cytotoxic activity of the CHR–AuNPs preparation has the potential for clinical use after considerable appropriate developments.
The aim of current study was investigated the effects of chrysin supplementation (10 mg/kg, per oral, p.o.) over 28 days in a model of Parkinson’s disease (PD) induced by 6-hydroxydopamine (6-OHDA), ...using C57BL/6 male mice. Intrastriatal 6-OHDA microinjection caused oxidative stress, impairment of antioxidant defenses, depletion of dopamine (DA) and its metabolites, loss of tyrosine hydroxylase neurons (TH+) of substantia nigra pars compacta (SNpc) and behavioral changes. Chrysin supplementation protect against oxidative stress and depletion antioxidant defenses. Moreover, supplementation with chrysin prevented the decrease of DA and its metabolites, corroborating protection against loss of TH+ neurons in SNpc, blocking behavioral changes induced by 6-OHDA.
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•Chrysin supplementation blocked neurobehavioral alterations induced by 6-OHDA.•Chrysin supplementation protected against loss of TH+ neurons.•Supplementation of chrysin prevented decrease of dopamine levels.
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