Distribution of Main Bioactive Compounds from Saffron Species as a Function of Infusion Temperature and Time in an Oil/Water System.

Most research on saffron has focused on its composition and beneficial effects, while the culinary perspective to enhance its gastronomic potential remains unexplored. This study aims to define the transfer of the main compounds responsible for color, flavor, and aromatic properties, evaluating three critical variables: temperature (60 °C, 80 °C and 100 °C), infusion time (ranging from 10 to 30 min), and the composition of the medium (water, oil, and water/oil). Samples were analyzed using the LC-QTOF MS/MS and ISO 3632-1:2011 methods. The major compounds were crocins, including trans-crocin and picrocrocin. Among the flavonoids, kaempferol 3-O-sophoroside stands out. Regarding extraction conditions, crocins, glycoside flavonoids, and picrocrocin were enhanced in water, the former in 100% water and at low temperatures, while picrocrocin proved to be the most stable compound with extraction favored at high temperatures. The variable with the greatest incidence of picrocrocin isolation seemed to be the concentration of water since water/oil compositions reported higher concentrations. Safranal and kaempferol were enriched in the oil phase and at lower temperatures. This study provides a chemical interpretation for the appropriate gastronomic use of saffron according to its versatility. Finally, the determination of safranal using the ISO method did not correlate with that obtained using chromatography.

A chemical analysis of the Pelargonium species: P. odoratissimum, P. graveolens, and P. zonale identifies secondary metabolites with activity against gram-positive bacteria with multidrug-resistance.

The Pelargonium genus encompasses around 280 species, most of which are used for medicinal purposes. While P. graveolens, P. odoratissimum, and P. zonale are known to exhibit antimicrobial activity, there is an evident absence of studies evaluating all three species to understand their chemical differences and biological effects. Through the analysis of the hydroalcoholic extracts of P. graveolens, P. odoratissimum, and P. zonale, using HPLC-DAD-MS/MS, quercetin and kaempferol derivatives were identified in these three species. Conversely, gallotannins and anthocyanins were uniquely detected in P. zonale. P. graveolens stood out due to the various types of myricetin derivatives that were not detected in P. odoratissimum and P. zonale extracts. Evaluation of their biological activities revealed that P. zonale displayed superior antibacterial and antibiofilm activities in comparison to the other two species. The antibacterial efficacy of P. zonale was observed towards the clinically relevant strains of Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus (MRSA) 333, Enterococcus faecalis ATCC 29212, and the Vancomycin-resistant E. faecalis INSPI 032. Fractionation analysis of P. zonale suggested that the antibacterial activity attributed to this plant is due to the presence of quercetin derivatives and kaempferol and its derivatives, alongside their synergistic interaction with gallotannins and anthocyanins. Lastly, the three Pelargonium species exhibited notable antioxidant activity, which may be attributed to their high content of total phenolic compounds.

Potential anti-liver cancer targets and mechanisms of kaempferitrin based on network pharmacology, molecular docking and experimental verification.

AIM: Kaempferitrin is an active component in Chenopodium ambrosioides, showing medicinal functions against liver cancer. This study aimed to identify the potential targets and pathways of kaempferitrin against liver cancer using network pharmacology and molecular docking, and verify the essential hub targets and pathway in mice model of SMMC-7721 cells xenografted tumors and SMMC-7721 cells. METHODS: Kaempferitrin therapeutical targets were obtained by searching SwissTargetPrediction, PharmMapper, STITCH, DrugBank, and TTD databases. Liver cancer specific genes were obtained by searching GeneCards, DrugBank, TTD, OMIM, and DisGeNET databases. PPI network of "kaempferitrin-targets-liver cancer" was constructed to screen the hub targets. GO, KEGG pathway and MCODE clustering analyses were performed to identify possible enrichment of genes with specific biological subjects. Molecular docking and molecular dynamics simulation were employed to determine the docking pose, potential and stability of kaempferitrin with hub targets. The potential anti-liver cancer mechanisms of kaempferitrin, as predicted by network pharmacology analyses, were verified by in vitro and in vivo experiments. RESULTS: 228 kaempferitrin targets and 2186 liver cancer specific targets were identified, of which 50 targets were overlapped. 8 hub targets were identified through network topology analysis, and only SIRT1 and TP53 had a potent binding activity with kaempferitrin as indicated by molecular docking and molecular dynamics simulation. MCODE clustering analysis revealed the most significant functional module of PPI network including SIRT1 and TP53 was mainly related to cell apoptosis. GO and KEGG enrichment analyses suggested that kaempferitrin exerted therapeutic effects on liver cancer possibly by promoting apoptosis via p21/Bcl-2/Caspase 3 signaling pathway, which were confirmed by in vivo and in vitro experiments, such as HE staining of tumor tissues, CCK-8, qRT-PCR and Western blot. CONCLUSION: This study provided not only insight into how kaempferitrin could act against liver cancer by identifying hub targets and their associated signaling pathways, but also experimental evidence for the clinical use of kaempferitrin in liver cancer treatment.

From Ethnobotany to Biotechnology: Wound Healing and Anti-Inflammatory Properties of Sedum telephium L. In Vitro Cultures.

Sedum telephium is a succulent plant used in traditional medicine, particularly in Italy, for its efficacy in treating localized inflammation such as burns, warts, and wounds. Fresh leaves or freshly obtained derivatives are directly applied to the injuries for these purposes. However, challenges such as the lack of microbiologically controlled materials and product standardization prompted the exploration of more controlled biotechnological alternatives, utilizing in vitro plant cell cultures of S. telephium. In the present study, we used HPLC-DAD analysis to reveal a characteristic flavonol profile in juices from in vivo leaves and in vitro materials mainly characterized by several kaempferol and quercetin derivatives. The leaf juice exhibited the highest content in total flavonol and kaempferol derivatives, whereas juice from callus grown in medium with hormones and callus suspensions showed elevated levels of quercetin derivatives. The in vitro anti-inflammatory and wound-healing assays evidenced the great potential of callus and suspension cultures in dampening inflammation and fostering wound closure, suggesting quercetin may have a pivotal role in biological activities.

Solid lipid nanoparticle: A potent vehicle of the kaempferol for brain delivery through the blood-brain barrier in the focal cerebral ischemic rat.

Kaempferol is major flavonoid present in Convolvulus pluricaulis. This phytochemical protects the brain against oxidative stress, neuro-inflammation, neurotoxicity, neurodegeneration and cerebral ischemia induced neuronal destruction. Kaempferol is poorly water soluble. Our study proved that solid lipid nanoparticles (SLNs) were efficient carrier of kaempferol through blood-brain barrier (BBB). Kaempferol was incorporated into SLNs prepared from stearic acid with polysorbate 80 by the process of ultrasonication. Mean particle size and zeta potential of kaempferol loaded solid lipid nanoparticles (K-SLNs) were 451.2 nm and -15.0 mV. Atomic force microscopy showed that K-SLNs were spherical in shape. Fourier transformed infrared microscopy (FTIR) showed that both stearic acid and kaempferol were present in K-SLNs. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed that the matrices of K-SLNs were in untidy crystalline state. Entraptment efficiency of K-SLNs was 84.92%. In-vitro drug release percentage was 93.24%. Kaempferol loaded solid lipid nanoparticles (K-SLNs) showed controlled release profile. In-vitro uptake study showed significant efficiency of K-SLNs to cross blood-brain barrier (BBB). After oral administration into the focal cerebral ischemic rat, accumulation of fluorescent labeled K-SLNs was observed in the brain cortex which confirmed its penetrability into the brain. It significantly decreased the neurological deficit, infarct volume and level of reactive oxygen species (ROS) and decreased the level of pro-inflammatory mediators like NF-κB and p-STAT3. Damaged neurons and brain texture were improved. This study indicated increased bioavailability of kaempferol into the brain tissue through SLNs formulation.

Mechanism of Astragalus membranaceus (Huangqi, HQ) for treatment of heart failure based on network pharmacology and molecular docking.

Heart failure is a leading cause of death in the elderly. Traditional Chinese medicine, a verified alternative therapeutic regimen, has been used to treat heart failure, which is less expensive and has fewer adverse effects. In this study, a total of 15 active ingredients of Astragalus membranaceus (Huangqi, HQ) were obtained; among them, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol were found to be linked to heart failure. Ang II significantly enlarged the cell size of cardiomyocytes, which could be partially reduced by Quercetin, Isorhamnetin, Calycosin, Kaempferol, or Formononetin. Ang II significantly up-regulated ANP, BNP, ß-MHC, and CTGF expressions, whereas Quercetin, Isorhamnetin, Calycosin, Kaempferol or Formononetin treatment partially downregulated ANP, BNP, ß-MHC and CTGF expressions. Five active ingredients of HQ attenuated inflammation in Ang II-induced cardiomyocytes by inhibiting the levels of TNF-α, IL-1ß, IL-18 and IL-6. Molecular docking shows Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol can bind with its target protein ESR1 in a good bond by intermolecular force. Quercetin, Calycosin, Kaempferol or Formononetin treatment promoted the expression levels of ESR1 and phosphorylated ESR1 in Ang II-stimulated cardiomyocytes; however, Isorhamnetin treatment had no effect on ESR1 and phosphorylated ESR1 expression levels. In conclusion, our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HQ against heart failure. Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure through regulating ESR1 expression, which provided a basis for the clinical application of HQ to regulate cardiac hypertrophy and heart failure.

Polydopamine-Coated Kaempferol-Loaded MOF Nanoparticles: A Novel Therapeutic Strategy for Postoperative Neurocognitive Disorder.

Purpose: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery. Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress. Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation. Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.

Kaempferol Derivatives from Hippophae rhamnoides Linn. Ameliorate H2O2-Induced Oxidative Stress in SH-SY5Y Cells by Upregulating Nrf2.

As a medicinal and edible resource, Hippophae rhamnoides Linn. subsp. sinensis Rousi is rich in bioactive secondary metabolites, including flavonoids and their derivatives, which offer protective effects against oxidative damage. This study reported the isolation of three new kaempferol derivatives from the seed residue of H. rhamnoides - Hippophandine A, B, and C (compounds 1-3). Their structures were elucidated by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR), and chemical analyses. The compounds were evaluated for their ability to mitigate hydrogen peroxide (H2O2)-induced cell death in SH-SY5Y cells. The results elucidated that Hippophandine A-C at concentrations of 1, 5, and 10 µM reduced the levels of malondialdehyde (MDA) and increased the activity of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, they significantly altered the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1), which is an indicator of redox detection in H2O2-induced SH-SY5Y.

Triple Sensing Modes for Triggered ß-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.

Establishing aqueous two-phase flotation coupled with preparative high performance liquid chromatography and its application for the purification of astragalin from Flaveria bidentis.

The strategy of aqueous two-phase flotation (ATPF) followed by preparative high performance liquid chromatography (prep-HPLC) was established and used for the separation of astragalin from Flaveria bidentis. In the ATPF, the effects of sublation solvent, solution pH, (NH4)2SO4 concentration in aqueous solution, cosolvent, N2 flow rate, flotation time and volumes of the PEG phase on the recovery of astragalin were investigated in detail, and the optimal conditions of ATPF were selected: 50 wt% PEG1000 ethanol solvent as the flotation solvent, pH 4, 350 g/L of (NH4)2SO4 concentration in 5 % ethanol aqueous phase, 40 mL/min of N2 flow rate, 30 min of flotation time, 10.0 mL of flotation solvent volume and twice. After ATPF enrichment, the flotation product was further purified by prep-HPLC. As determined by HPLC, the purity of astragalin was 98.8 %.

Simultaneous assessment of absorption and pharmacokinetic characteristics of four active flavonoids from Chimonanthus nitens Leaf Granules using LC-MS determination: in vivo and in vitro.

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.

Flavonoid glycosides from the leaves of Michelia champaca.

Michelia champaca L. (Magnoliaceae) was cultivated in large scale for flowers as cosmetic raw materials, whereas the value of its leaves remains to be discovered. Our chemical study on the leaves yielded four new flavonol diglycosides, champaflavosides A-D (1-4), together with twenty-three known flavonoid glycosides (5-27). Their structures were determined by spectroscopic and chemical methods. Compounds 5-21 and 23-27 were not previously reported from the genus Michelia, and kaempferol 3-O-rutinoside (22) was obtained from this species for the first time. All the compounds were evaluated for antioxidant activity by four in vitro assays. Compounds 3-12 and 20 showed more potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than l-ascorbic acid (l-AA). Compounds 2-23, 25, and 27 exhibited 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity superior to l-AA. The ferric reducing antioxidant powers (FRAP) of compounds 2-13, 17, and 19 were higher than l-AA. Further, eighteen compounds demonstrated cellular reactive oxygen species (ROS) scavenging activity, of which champaflavoside D (4), rhamnetin 3-O-neohesperidoside (8), quercetin 3-O-(6-O-E-p-coumaroyl)-neohesperidoside (9), and liquiritin (27) were more potent than curcumin. The results revealed that the renewable leaves of M. champaca are a rich source of flavonoids and antioxidants.

Kaempferol: Paving the path for advanced treatments in aging-related diseases.

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the ß-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.

Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis Target of Kaempferol.

BACKGROUND: Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. OBJECTIVE: The study aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. METHODS: Differential expression analysis was conducted on disulfide-related genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116 dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. RESULTS: RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally high expression of RPN1 in the femur of ovariectomized rats. CONCLUSION: RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.

Fermentation of Robinia pseudoacacia flower for improving the antioxidation: optimized conditions, active composition, mechanism, and biotransformation process.

Robinia pseudoacacia flower is a natural product with many biological activities, including antioxidation. To further develop its antioxidation, the extract was fermented by Aspergillus niger FFCC 3112 in the medium with carbon to nitrogen ratio of 1.4:1 and initial pH of 4.2 for 3.5 days to form the best antioxidant activity of the fermentation product by strain screening, single factor optimization, and response surface methodology. Further analysis, isolation and activity determination showed that a main chemical component, kaempferol-3-O-α-L-rhamnopyranosyl-(1→6)-ß-D-galactopyranosyl-7-O-α-L-rhamnopyranoside, in the extract was completely hydrolyzed to kaempferol-7-O-α-L-rhamnopyranoside and kaempferol with better antioxidant activity through biotransformation, which was the basis for improving the antioxidant activity of fermentation products. Moreover, the mechanism of antioxidant and the contribution of phenolic hydroxyl groups were investigated by density functional theory. The result indicated that the antioxidant capacity of kaempferol-7-O-α-L-rhamnopyranoside and kaempferol increased with the increase of solvent polarity. In high-polarity solvents, they mainly scavenge free radicals through single electron transfer followed by proton transfer.

Screening and Inhibition Mechanism of Xanthine Oxidase Inhibitors in Ethanolic Extracts of Chimonanthus salicifolius Hu Leaves.

This study aimed to evaluate the inhibition of the ethanol elutions of Chimonanthus salicifolius Hu leaves (CsHL) against xanthine oxidase (XO). The results of XO inhibition assay and enzymatic superoxide free radical scavenging assay in vitro showed that 70 % ethanol eluate (EE) had the best inhibitory effect and followed by 40 % EE. High performance liquid chromatograph analysis showed that quercetin and kaempferol were the potential active components of XO inhibition. The inhibition mechanism of quercetin and kaempferol on XO was investigated by kinetic analysis and fluorescence quenching titration assay. The molecular simulation further revealed that quercetin and kaempferol bind to XO mainly by hydrogen bonding and van der Waals, blocking the entry of substrates and leading to the inhibition of XO. In conclusion, the CsHL have inhibitory effects on XO activity, which provides a theoretical basis for relieving or preventing hyperuricemia and gout as a natural food or medicinal plant in the future.

Comparative analysis of the reactivity of anthocyanidins, leucoanthocyanidins, and flavonols using a quantum chemistry approach.

Anthocyanidins, leucoanthocyanidins, and flavonols are natural compounds mainly known due to their reported biological activities, such as antiviral, antifungal, anti-inflammatory activities, and antioxidant activity. In the present study, we performed a comparative structural, conformational, electronic, and nuclear magnetic resonance analysis of the reactivity of the chemical structure of primary anthocyanidins, leucoanthocyanidins, and flavonoids. We focused our analysis on the following molecular questions: (i) differences in cyanidin catechols ( +)-catechin, leucocyanidin, and quercetin; (ii) the loss of hydroxyl presents in the R1 radical of leucoanthocyanidin in the functional groups linked to C4 (ring C); and (iii) the electron affinity of the 3-hydroxyl group (R7) in the flavonoids delphinidin, pelargonidin, cyanidin, quercetin, and kaempferol. We show unprecedented results for bond critical point (BCP) of leucopelargonidin and leucodelphirinidin. The BCP formed between hydroxyl hydrogen (R2) and ketone oxygen (R1) of kaempferol has the same degrees of covalence of quercetin. Kaempferol and quercetin exhibited localized electron densities between hydroxyl hydrogen (R2) and ketone oxygen (R1). Global molecular descriptors showed quercetin and leucocyanidin are the most reactive flavonoids in electrophilic reactions. Complementary, anthocyanidins are the most reactive in nucleophilic reactions, while the smallest gap occurs in delphinidin. Local descriptors indicate that anthocyanidins and flavonols are more prone to electrophilic attacks, while in leucoanthocyanidins, the most susceptible to attack are localized in the ring A. The ring C of anthocyanidins is more aromatic than the same found in flavonols and leucoanthocyanidins. METHODS: For the analysis of the molecular properties, we used the DFT to evaluate the formation of the covalent bonds and intermolecular forces. CAM-B3LYP functional with the def2TZV basis set was used for the geometry optimization. A broad analysis of quantum properties was performed using the assessment of the molecular electrostatic potential surface, electron localization function, Fukui functions, descriptors constructed from frontier orbitals, and nucleus independent chemical shift.

Structural characterization and stability of glycated bovine serum albumin-kaempferol nanocomplexes.

Kaempferol (Kae), a flavonoid is endowed with various functions. However, due to its poor water solubility and stability, its application in the food and pharmaceutical fields remains elusive. Emerging reports have emphasized the importance of bovine serum albumin (BSA), and glycosylated BSA (GBSA) prepared in the nature deep eutectic solvent system as drug delivery system carriers. In our study, ultraviolet and fluorescence spectra revealed the higher interactions of BSA and GBSA with Kae. Through analysis of Z-average diameter, zeta-potential, polydispersity index (PDI), encapsulation efficiency (EE), loading capacity (LC) of BSA-Kae nanocomplexes (NPs) and GBSA-Kae NPs, GBSA-Kae NPs showed a higher absolute value of zeta-potential and lower PDI, while its EE and LC were also higher. Structural characterization and stability analysis revealed that GBSA-Kae NPs had more stable properties. This study laid the theoretical foundation for improving the solubility and stability of Kae during its delivery and transport.

Comparative study on the interaction between transferrin and flavonols: Experimental and computational modeling approaches.

Transferrin is the indispensable component in the body fluids and has been explored as a potential drug carrier for target drugs to cancer cells. Flavonols are widely distributed in plants and shown a wide range of biological activities. In the present study, the interaction between flavonols (including galangin, kaempferol, quercetin, and myricetin) and transferrin under physiological conditions was investigated by using experimental as well as computational approaches. Fluorescence data reveal that the fluorescence quenching mechanism of transferrin by flavonols is static quenching. Transferrin has moderate affinity with flavonols, and the binding constants (Ka) are 103-104 L/mol. In addition, there are two different binding sites for the interaction between kaempferol and transferrin. Thermodynamic parameter analysis shows that the interaction of flavonols and transferrin is synergistically driven by enthalpy and entropy. Hydrophobic interaction, electrostatic force and hydrogen bonds are the main force types. Synchronous fluorescence spectroscopy shows that flavonols decrease the hydrophobicity of the microenvironment around tryptophan (Trp) and have no effect on the microenvironment around tyrosine (Tyr). UV-vis and CD spectra show that the interaction between transferrin and flavonols leads to the loosening and unfolding of transferrin backbone. The increase of ß-sheet is accompanied by the decrease of α-helix and ß-turn. The specific binding sites of flavonols to transferrin are confirmed by molecular docking. Molecular dynamic simulation suggests that the transferrin-flavonols docked complex is stable throughout the simulation trajectory.