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The sliced and dried hawthorn berries are easily infested by insects during storage. This study aimed to determine the effect of insect infestation on the quality of hawthorn berries and assess the change at metabolite level by analyzing physicochemical property and metabolomics profiling. A total of 184 shared differential metabolites were obtained, mainly including flavonoids, fatty acids, carboxylic acids and derivatives, and nitrogenous compounds. Through receiver operating characteristic curve assessment, 9 significant differential markers were screened out to distinguish insect infestation of hawthorn berries. Correlation analysis showed that the color, total organic acids, total phenolics, and total flavonoids were effective indicators for quality evaluation of insect infestation, and uric acid and hippuric acid can serve as biomarkers for the quality deterioration of hawthorn berries during storage. This study demonstrated that insect infestation could decrease the quality of hawthorn berries from macro and micro perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, sufaid chonsa mango pulp aqueous extracts from different ripening stages (RS I-V) was utilized to synthesize silver nanoparticles (Ag NPs). The Ag NPs were characterized using UV-vis spectrometry, X-ray diffraction analysis (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy dispersice X-ray analysis (EDX). Additionally, antioxidative potential and phenolic and flavonoid-like properties of synthesized Ag NPs were also accessed. UV-vis spectrophotometer analysis showed peaks in around 400 nm. XRD analysis confirmed the crystalline structure of the green-synthesized Ag NPs, with sizes ranging from 2.11 to 11.72 nm. FTIR verified the attachment of functional groups from the mango pulp extract to the Ag NPs. SEM analyses revealed that the morphology of the Ag NPs was primarily spherical that were agglomerated. The total antioxidant capacity, measured by the DPPH assay, showed 51% radical scavenging activity for RSIII extract synthesized NPs. The highest total antioxidant capacity was observed to be 80.22 and 79.14 µg AAE/mg NPs by RSI and RSIV synthesized NPs, respectively, while the maximum total reduction potential was 28.67 µg AAE/mg for Ag NPs synthesized by RSII extract. Ag NPs derived from RSIV exhibited phenolic-like property of 70.84 µg GAE/mg, while those derived from RSII had a maximum flavonoid-like property of 35.37 µg QE/mg. This study demonstrates that mango pulp at different ripening stages produces Ag NPs with distinct characteristics, making them suitable for various environmental and biomedical applications., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Ajuga turkestanica preparations are used as anti-aging cosmeceuticals and for medicinal purposes. Herein we describe the characterization and quantification of its metabolites in different organs using UHPLC-MS and NMR spectroscopy. A total of 51 compounds belonging to various phytochemical classes (11 flavonoids, 10 ecdysteroids, 9 diterpenes, 6 fatty acids, 5 iridoids, 3 phenylpropanoids, 3 sugars, 2 phenolics, 1 coumarin, 1 triterpene) were annotated and tentatively identified by UHPLC-ESI-QqTOF-MS/MS of methanolic extracts obtained separately from the organs. 1D and 2D NMR spectroscopy independently confirmed the identity of six major compounds. The abundances of these main constituents in flowers, fruits, leaves, roots, seeds, and stems were compared and quantified using 1 H NMR. The results showed that 8-O-acetylharpagide, 20-hydroxyecdysone (ecdysterone) and ajugachin B were the most abundant constituents in the species. The two major compounds, 8-O-acetylharpagide and 20-hydroxyecdysone, were chosen as the markers for the quality assessment of A. turkestanica material. The methanolic extract of the aerial parts of A. turkestanica showed no noteworthy anthelmintic (antihelmintic), antifungal, or cytotoxic effect in in vitro assays., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

With the developing resistance to traditional antiparasitic medications, the purpose of this study was to efficiently develop a series of six noble flavanoidal tetrazinane-6'-one derivatives by a one-pot reaction pathway. FT-IR, 1 HNMR, 13 CNMR, and Mass spectra were employed for the structural elucidation of the synthesized compounds (7-12). Clinostomum complanatum, a parasite infection model that has been well-established, demonstrated that all the synthesized compounds are potent antiparasitic agents. DNA is the main target for various medicinal compounds. As a result, thestudy of how small molecules attach to DNA has received a lot of attention. In the present study, we have performed various biophysical techniques to determine the mode of binding of synthesized compounds (7-12) with calf thymus DNA (ct-DNA). It was observed from the UV-visible absorbance and fluorescence spectra that all synthesized compounds (7-12) form complexes with the ct-DNA. The value of binding constant (K b ) was obtained to be in the range of 4.36---24.50 × 10 3 M - 1 at 298 K. Competitive displacement assay with ethidium bromide (EB), CD spectral analysis, viscosity measurements, and in silico molecular docking confirmed that ligands (7-12) incorporate with ct-DNA through groove binding only. Molecular docking studies were performed for all synthesized compounds with the calf thymus DNA and it was found that all the newly synthesized compounds strongly bind with the chain B of DNA in the minor groove with the value of binding energy in the range of -8.54 to -9.04 kcal per mole and several hydrogen bonding interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Kombucha was fermented by the pure cultured tea fungus, and the changes of functional compounds and their transformation were explored. After fermentation, the contents of total polyphenols, total flavonoids, quercetin, kaempferol and catechins respectively enhanced by 77.14%, 69.23%, 89.11%, 70.32% and 45.77% compared with the control, while flavonol glycosides reduced by 38.98%. The bioavailability of polyphenols and flavonoids respectively increased by 29.52% and 740.6%, and DPPH and ABTS respectively increased by 43.81% and 35.08% compared with the control. Correlation analysis showed that microorganisms and the antioxidant activity were highly positive correlation with total polyphenols, total flavonoids, EGC, EC, EGCG, ECG, quercetin and kaempferol, and negative correlation with kaempferol-3-glucoside. The constructed models confirmed that organic acids were more likely to damage the structure of tea leaves, and enzymes (polygalacturonidase and tannase) and solvents (acids, alcohols and esters) had a synergistic effect on the biotransformation of functional compounds., Competing Interests: Declaration of competing interest The authors confirm that they have no conflicts of interest with respect to the work described in this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A series of myricetin derivatives containing diisopropanolamine were designed and synthesized. The in vitro inhibitory effects of the target compounds on 9 fungal pathogens and 3 bacterial pathogens were also evaluated. A12 had the best inhibitory effect against Xanthomonas oryzae pv. oryzae ( Xoo ), with an EC 50 value of 4.9 μg/mL, which was better than zinc-thiazole (ZT: EC 50 = 7.3 μg/mL) and thiodiazole-copper (TC: EC 50 = 65.5 μg/mL); A25 had the best inhibitory effect against Phomopsis sp . ( Ps ), with an EC 50 value of 17.2 μg/mL, which was better than azoxystrobin (Az: EC 50 = 22.3 μg/mL). In vivo inhibition tests were performed on kiwifruit for A25 and rice leaves for A12 . At 200 μg/mL, the curative activity of A12 against rice leaf blight was 40.7%, which was better than that of ZT (37.2%) and TC (32.9%), and the protective activity of A12 was 44.8%, which was better than that of ZT (39.5%) and TC (34.6%). The curative activity of A25 against kiwi soft rot disease was 70.1%, which was better than that of Az (62.8%). Preliminary elucidation of the possible mechanisms of action was carried out by experiments on fluorescence microscopy, scanning electron microscopy, formation of biofilms, density functional theory calculations, and so on.

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amin Sahraei and Reza Sahraei report financial support was provided by Iran National Science Foundation (INSF). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The characterization of plant extracts is usually accomplished by reverse-phase liquid chromatography, but the development of new complementary approaches, such as HILIC, offers an orthogonal method. In this study, five HILIC stationary phases were evaluated to assess their ability to retain polyphenols. They were selected to cover the main different HILIC mechanisms: bare silica; silica with ethylene bridge; neutral amide; amino; zwitterionic. A total of 31 polyphenol standards were used for the screening, including 9 stilbenes, 8 flavonoids, 6 anthocyanins, and 8 phenolic acids. Three different detections were tested: diode array detector, charged aerosol detector and mass spectrometry. Results indicated that silica supports were not suitable for retaining polyphenols, with no or low retention observed except for anthocyanins. The effectiveness of stationary phases in retention of phenolics following the order related to increased retention: zwitterionic, amide, and amino. The choice of mobile phase also influenced retention. Mobile phases containing TFA as pH modifier limited retention, while formic acid was found to be more effective for polyphenol retention. Ammonium buffers also improved retention but often compromised peak shape. pH changes mainly impacted ionizable compounds, such as phenolic acids, by increasing their retention when they were ionized. DAD was wellsuited for detecting polyphenols that possess aromatic rings, though peak wavelengths depend on the structures of the polyphenols. CAD, while less sensitive than DAD and MS, provided an almost similar response for structurally related compounds, even with gradient elution. MS was the preferred detector for quantification when resolution between compounds was challenging, as it is often the case with natural extracts. The study successfully demonstrated that best HILIC conditions were obtained using an amino stationary phase composed of a polyethylenimine and formic acid-based mobile phase. These conditions were successfully applied to the analysis of stilbenoid-rich extracts from different parts of the vine. The elution order of stilbenoids followed the degree of polymerization. With CAD, the chromatographic profile was more representative of sample composition. It was demonstrated for the first time the interest of a combination of HILIC and CAD for analyzing stilbenes, offering a complementary approach to the classic RP analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Qing-Kai-Ling oral liquid is commonly used clinically for the treatment of fever and upper respiratory tract infection. Moreover, studies have shown that Qing-Kai-Ling oral liquid has an anti-pneumonia effect. However, owing to its complex pharmacodynamic material basis, its pharmacological research and clinical application are limited. To address this problem, the chemical constituents of Qing-Kai-Ling oral liquid were identified by ultra-high performance liquid chromatography quadrupole-Exactive Orbitrap mass (UHPLC-Q-Exactive Orbitrap MS) and network pharmacology methods, which were used to predict its potential anti-pneumonia target and signalling pathway. A total of 150 compounds were identified and tentatively characterized, including 35 amino acids and their derivatives, 36 organic acids, 20 terpenoids, 20 alkaloids, 12 glycosides, 7 flavonoids, and 20 others. Among them, 14 compounds were accurately identified by comparing their retention time and mass spectrum data with those of reference substances. Additionally, we performed molecular simulation calculations via Density Function Theory to determine the plausibility of the compound cleavage reactions and further confirm compound structures. Furthermore, 90 key targets were screened through network pharmacology, with the particular focus on the PI3K-AKT, MAPK and TNF signalling pathways. This method achieved the first comprehensive identification of the chemical composition of Qing-Kai-Ling oral liquid and elucidated its potential mechanism of anti-pneumonia. The results provide valuable reference and data support for pharmacodynamic substance research and quality control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exploring the potential of natural products against diabetes and obesity is in demand nowadays. Pancreatic α-amylase and pancreatic lipase are the drug targets to minimize the absorption of glucose from starch and fatty acids from lipids, respectively. In this study, five Piper species, namely P. sarmentosum (Ps), P. wallichii (Pw), P. retrofractum (Pr), P. nigrum (Pn), and P. betle (Pb), which are commonly used as food ingredients and traditional medicines, were evaluated for their inhibitory activities against pancreatin using the microtiter plate method. Additionally, pancreatin inhibitors were identified through a cost-effective high-performance thin-layer chromatography (HPTLC)-bioautography developed using red starch and p-nitrophenyl palmitate, corresponding to anti-amylase and -lipase activities, respectively. Of the 15 samples tested, leaf samples from Pb, which had the highest total phenolic and total flavonoid contents, exhibited remarkable inhibitory activity against pancreatin, with a relative amylase inhibitory capacity (RAIC) ranging between 4.260 × 10 -5 and 4.861 × 10 -5 and a reciprocal half-maximal inhibitory concentration (1/IC 50 , PTL) of 0.390-0.510 (mg/mL) -1 . Additionally, Ps samples demonstrated the second-ranked anti-pancreatin activity. Principal component analysis indicated that total phenolic content contributed to the anti-pancreatin activities of Pb samples. The anti-pancreatin bands were isolated and identified as caffeic acid, myricetin, genistein, piperine, and eugenol. Myricetin, in the roots of Ps samples, showed notable anti-pancreatin activity, which was consistent with results from the in silico prediction toward pancreatic α-amylase and pancreatic lipase. Caffeic acid and eugenol were present in Pb samples. In conclusion, the developed cost-effective pancreatin HPTLC-bioautography efficiently identified amylase and lipase inhibitors from Piper herbs, which supported the use of these plants for antidiabetes and anti-obesity., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Akkermansia muciniphila ( A. muciniphila ) possesses health-promoting properties. Nevertheless, A. muciniphila enrichment remains a challenging endeavor. Quercetin-3- O -rutinose-7- O -α-l-rhamnoside (QRR), a flavonoid found in lychee pulp, has a unique double-substituted glycosylated structure, requiring a specific intestinal microbiota for effective metabolism. Here, QRR was fermented using a coculture of Bacteroides uniformis and A. muciniphila , and the interactions between the two were elucidated in terms of QRR regulation of microbial growth changes and metabolic properties. The results demonstrated that QRR effectively promoted the proliferation of A. muciniphila based on the metabolic action of B. uniformis in vitro, which was evidenced by a notable increase in the number of viable bacteria. Furthermore, the coculture sample exhibited a significant increase in SCFAs. Qualitative analysis of metabolites by UPLC-ESI-Triple-TOF-MS/MS showed that B. uniformis could release sugars on QRR to produce quercetin-3- O -glucoside-7- O -α-rhamnoside and further quercetin. In the coculture and B. uniformis culture, quercetin was converted to taxifolin, which was identified as a crucial intermediate in the metabolism of QRR. Notably, the metabolite kaempferol was only detected in the coculture. The present study reveals the interaction between QRR and the coculture of A. muciniphila and B. uniformis , providing a practical basis for the potential prebiotic value of QRR.

Growing evidence has unveiled the pathological significance of Tau in many cancers, including the most aggressive and lethal brain tumor glioblastoma multiform (GBM). In this regard, we have recently examined the structure-activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau-overexpressing GBM cells. Here, we evaluated the anticancer activities of the two lead compounds 2 and 9 using multi-cellular spheroids (MCSs) which represent an easy 3D human cell model to mimic GBM organization, physical constraints and drug penetration. The two compounds reduced cell evasion from spheroids up to three times, especially for Tau-expressing cells. As a first step towards a therapeutic approach, we quantified the effects of these compounds on MCS growth using two complementary protocols: single and repeated treatments. A single injection with compound 9 slowed down the growth of MCSs formed with U87 shCTRL cells by 40% at 10 µM. More interestingly, multiple treatment with compound 9 slowed the growth of U87 shCTRL spheroids by 40% at a concentration of 5 µM, supporting the increased bioavailability of compound 9 within MCSs. In conclusion, compound 9 deserves particular attention as promising candidate for specifically targeting Tau-expressing cancers such as GBM.

Introduction: Phyto-nanotechnology offers a sustainable method for synthesizing biocompatible metal nanoparticles (NPs) with therapeutic potential. The diverse medicinal flora in the UAE, particularly Leptadenia pyrotechnica (LP), provides a vital resource for advancing this research area. This plant is historically valued in the region for its wide medicinal applications due to its abundance of bioactive compounds., Methods: In this study, eco-friendly, straightforward, and low-temperature hydrothermal synthesis methods were applied to synthesize potentially therapeutic Zn and Fe NPs using LP extracts. The generated NPs were characterized using UV-VIS, FT-IR, SEM, EDX, XRD and DLS. Moreover, they were investigated for their total phenolic and flavonoid contents, along with their antioxidant and skin anticancer effects., Results: The UV-Vis spectra disclosed absorption band at about 275 nm, and the FT-IR confirmed the successful coating of the NPs with the plants' phytochemicals, thus ensuring the successful bio-fabrication of the proposed NPs. SEM/EDX outcomes suggest a more potent reducing effect of the aqueous extract, while a more effective coating of the alcoholic extract. DLS revealed monodispersed NPs, with average sizes ranging from 43.82 to 207.8 nm. LFeC demonstrated the highest phenolic and flavonoid contents (49.96±4.76 μg of GAE/mg of DW and 43.89±2.89 μg of Qu/mg of DW, respectively) and the greatest potency against skin cancer cell lines (IC 50 =263.56 µg/mL). However, LZnC exhibited the strongest radical scavenging effect against DPPH and ABTS radicals (IC 50 =139.45µg/mL and 35.1µg/mL, respectively)., Discussion: The results of this study demonstrated that both extracts of LP are effective in the green synthesis of Fe and Zn nanoparticles for biomedical applications, with alcoholic extracts providing superior coating, capping, and stabilizing properties, leading to lower agglomeration, higher carbon content, total phenolic and flavonoid contents, along with enhanced anticancer and antioxidant effects. This work gives a showcase of sustainable materials that are promising for therapeutic applications., Competing Interests: The authors declare no competing interests in this work., (© 2024 El-Fitiany et al.)

Despite the enormous importance of chromone and flavonoid piperidine alkaloids, a general method for their synthesis has not been described. Accordingly, from simple tetrahydro-3-pyridinemethanols ( A ) and phenol derivatives ( B ), a synthetic approach to chromone and flavonoid piperidine alkaloids is presented. The access to a novel chromone and flavonoid alkaloid precursors 4-(2-hydroxyphenyl)-3-methylenepiperidines ( C ) is achieved in only two steps: Mitsunobu reaction followed by an intramolecular C-H phenolization via an aromatic Claisen rearrangement of the respective Mitsunobu adducts ( D ). Consequently, the simultaneous installation of the functionalized phenol group and the exo-methylene group within the piperidine skeleton, permits, not only the easy construction of the chromone or flavonoid cores but also the simultaneous installation of the hydroxyl group with the required cis -orientation. Additionally, the synthetic utility of this novel approach is showcased in the formal synthesis of flavopiridol, rohitukine, and their N -Moc analogues.

Introduction: The incidence of inflammatory bowel disease (IBD) has been increasing year by year in recent years. Flavonoids are the main components of mulberry leaves exerting anti-inflammatory effects and have potential applications in drug screening for IBD treatment. Enzymatic hydrolysis can enhance the bioavailability and activity of flavonoid glycosides. No relevant reports on the potentiation of mulberry leaf flavonoids (MLF) after deglycosylation have been retrieved., Methods: An enzymatic method was used to prepare enzymatic hydrolysates of MLF (EMLF). The protective effect of EMLF on zebrafish with IBD was evaluated by observing zebrafish intestinal length and width, intestinal histopathological morphology, as well as neutrophil and goblet expression. Network pharmacology and metabolomics were performed to explore the mechanism of action of EMLF against IBD. Finally, the mechanism of EMLF against IBD was validated using Western Blot and real-time quantitative polymerase chain reaction (RT-qPCR)., Results: The EMLF was successfully prepared by hydrolyzing MLF with snailase for the first time, and the anti-inflammatory effect of EMLF was clarified to be superior to that of MLF in IBD zebrafish. The network pharmacology and metabolomics studies showed that the mechanism of EMLF for IBD may be related to regulation of purine metabolic pathway. The expression levels of adenosine deaminase (ADA), critical targets in purine metabolism, were significantly down-regulated, while the expression of adenine phosphoribosyltransferase (APRT) and xanthine dehydrogenase (XDH) was significantly increased when compared with the TNBS group., Conclusion: The results suggested that enzymatic deglycosylation is an effective measure to enhance the anti-inflammatory activity of MLF, which provides referable ideas and methods for the deep processing and utilization of natural drug resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Flavonoids, a diverse group of plant-derived secondary metabolites, have garnered significant attention for their potential anti-cancer properties. This review explores the role of flavonoids as inhibitors of DNA topoisomerases, key enzymes essential for DNA replication, transcription, and cell division. The article offers a comprehensive overview of flavonoid classification, biosynthesis, and their widespread natural occurrence. It further delves into the molecular mechanisms through which flavonoids exert their anti-cancer effects, emphasizing their interactions with topoisomerases. The review provides a thorough analysis of both in vitro and in vivo studies that highlight the topoisomerase inhibitory activities of various flavonoids and their derivatives. Key findings demonstrate that flavonoids can function as catalytic inhibitors, poisons, or DNA intercalators, affecting both type I and type II topoisomerases. The structure-activity relationships of flavonoids concerning their topoisomerase inhibitory potency are also examined. This review underscores the potential of flavonoids as promising lead compounds for the development of novel topoisomerase inhibitors, which could have important implications for cancer therapy. However, it also acknowledges the need for further research to fully understand the intricate interactions between flavonoids and topoisomerases within the cellular environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To address the challenges associated with prolonged traditional hot air drying (HAD) times and significant nutrient loss in cherries, this study employs ultrasound-assisted hot air drying (USA-HAD) technology. The study investigates the impacts of various ultrasound (US) frequencies, US powers, and hot air temperatures on the drying kinetics, physicochemical properties, texture attributes, and microstructure of cherries during drying. Cherry physicochemical quality serves as the evaluation criterion, with the entropy-weighted TOPSIS method used to identify the optimal drying parameters. The findings indicate that USA-HAD accelerates the drying process, reduces drying time, and enhances drying efficiency. In comparison to natural drying, USA-HAD significantly preserves polysaccharides, total phenolic content, total flavonoid content, and organic acids in cherries, while boosting antioxidant activity. Concurrently, it reduces color intensity, as well as the hardness, chewiness, and gumminess of dried cherry products. Microstructural observations under different drying methods reveal an increase in surface micropores and relatively intact tissue structure. Under conditions of 55°C, 48 W, and 28 kHz, cherries exhibit superior overall quality based on the TOPSIS relative closeness degree. This study offers practical insights for optimizing post-harvest processing of cherries. PRACTICAL APPLICATION: In this rapidly evolving era, the application of combination drying technology is clearly on the rise. The USA-HAD treated cherries had better nutritional and bioactive than HAD. The conclusions obtained indicate that the USA-HAD technology has more potential for development., (© 2024 Institute of Food Technologists.)

Xanthine oxidase (XO), which plays a key role in purine metabolism, is an important target enzyme for the prevention and treatment of hyperuricemia. Inhibitory activity against XO is a common criterion for the screening of compounds with potential anti-hyperuricemic activity. In this study, 22 XO inhibitors were used to construct a 3D-QSAR pharmacophore model. Subsequently, molecular docking and in vitro activity evaluations were used to identify strong XO inhibitors from a list of 2000 natural compounds. The interaction mechanisms of these compounds with XO were analyzed based on inhibition kinetics and multi-spectral analyses. The pharmacophore model was composed of three hydrogen bond receptors and a hydrophobic center. The screened compounds - Diosmetin, Fisetin, and Genistein - all showed good XO inhibitory activity, with IC 50 values of 1.86 ± 0.11 μM, 5.83 ± 0.08 μM, and 7.56 ± 0.10 μM, respectively. Kinetic analysis, fluorescence quenching assays, and molecular docking experiments showed that Diosmetin, Fisetin, and Genistein docked near the same active site of XO, mainly affecting the microenvironment of tryptophan residues. These molecules showed static binding to XO via hydrogen bonds, hydrophobic interactions, and van der Waals forces. Diosmetin and Genistein were competitive inhibitors, whereas Fisetin was a mixed inhibitor. Infrared spectroscopy showed that Diosmetin, Fisetin, and Genistein increased the α-helix content of XO from 7.4 % to 16.6 %, 21.4 %, and 11.2 %, respectively, thereby enhancing its stability. In summary, the pharmacophore model constructed in this study was accurate. The flavonoids Diosmetin, Fisetin, and Genistein effectively inhibited the activity of XO, and the amino acid residues LEU257, ILE353, and VAL259 played a key role in the interaction between the flavonoids and XO. These findings are of great significance for the screening and development of new XO inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Considering medicinal plants, natural products present in these plants are the best sources of medications for combating viral infection. The possible drug target against viral H1N1 influenza proteins lead to identification of selected secondary metabolites from potential plants Tinospora cordifolia, Ocimum sanctum, and Piper nigrum. On analysis of in vitro cell based antiviral activity of the selected plant extracts, an indication for a possible lead compound against neuraminidase activity was evident. Potent ligands were selected using drug docking and ADMET analysis, and the screened lead metabolites were ultimately identified as terpenoid (Columbin) and, flavonoid (Cubebin, and Apigenin). Among the selected ligands, the drug binding activity of Cubebin with all the 6 proteins of H1N1 influenza type A virus, HA (4r8w), NA (4qn7), M2 (3lbw), PA (4wsb), PB1 (2znl) and PB2 (3wil), was pronounced. In addition, physicochemical and pharmacokinetic parameters linked to absorption, distribution, metabolism, excretion and toxicity (ADMET) have been evaluated and corroborate with our in vitro results. Molecular dynamics modelling indicated Cubebin can be a potential phytochemical in a drug discovery pipeline for the development of neuraminidase inhibitors. Further studies can provide a possibility for an alternative therapy against Influenza viruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Flavonoids, a commonly consumed natural product, elicit health-benefits such as antioxidant, anti-inflammatory, antiviral, anti-allergic, hepatoprotective, anti-carcinogenic and neuroprotective activities. Several studies have reported the beneficial role of flavonoids in improving memory, learning, and cognition in clinical settings. Their mechanism of action is mediated through the modulation of multiple signalling cascades. This polypharmacology makes them an attractive natural scaffold for designing and developing new effective therapeutics for complex neurological disorders like Alzheimer's disease and Parkinson's disease. Flavonoids are shown to inhibit crucial targets related to neurodegenerative disorders (NDDs), including acetylcholinesterase, butyrylcholinesterase, β-secretase, γ-secretase, α-synuclein, Aβ protein aggregation and neurofibrillary tangles formation. Conserved neuro-signalling pathways related to neurotransmitter biogenesis and inactivation, ease of genetic manipulation and tractability, cost-effectiveness, and their short lifespan make Caenorhabditis elegans one of the most frequently used models in neuroscience research and high-throughput drug screening for neurodegenerative disorders. Here, we critically appraise the neuroprotective activities of different flavonoids based on clinical trials and epidemiological data. This review provides critical insights into the absorption, metabolism, and tissue distribution of various classes of flavonoids, as well as detailed mechanisms of the observed neuroprotective activities at the molecular level, to rationalize the clinical data. We further extend the review to critically evaluate the scope of flavonoids in the disease management of neurodegenerative disorders and review the suitability of C. elegans as a model organism to study the neuroprotective efficacy of flavonoids and natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Organic cation transporter 1 (OCT1, gene symbol: SLC22A1) is mainly responsible for the hepatic uptake of various cationic drugs, closely associated with drug-induced liver injury (DILI). Screening and identifying potent OCT1 inhibitors with little toxicity in natural products is of great value in alleviating OCT1-mediated liver injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions (FDIs). Our objective was to investigate potential inhibitors of OCT1 from 96 flavonoids, evaluate the hepatoprotective effects on retrorsine-induced liver injury, and clarify the structure-activity relationships of flavonoids with OCT1. Thirteen flavonoids exhibited significant inhibition (>50%) on OCT1 in OCT1-HEK293 cells. Among them, the five strongest flavonoid inhibitors (IC 50  < 10 μM), including α-naphthoflavone, apigenin, 6-hydroxyflavone, luteolin, and isosilybin markedly decreased oxaliplatin-induced cytotoxicity. In retrorsine-induced liver injury models, they also reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to different levels, the best of which was 6-hydroxyflavone. The pharmacophore model clarified that hydrogen bond acceptors at the 4,8,5' position might play a vital role in the inhibitory effect of flavonoids on OCT1. Taken together, our findings would pave the way to predicting the potential risks of flavonoid-related FDIs in humans and optimizing flavonoid structure to alleviate OCT1-mediated liver injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The flavonoid chrysin is an effective vascular Ca V 1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to Ca V 1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca 2+ antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the Ca V 1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular Ca V 1.2 channel blockers., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

In this study, it is the first that the Viticis Fructus (VF) was used as the raw material for extracting total flavonoids using the ultrasound-assisted enzyme extraction (UAE) method. Response surface methodology was employed to determine the optimal extraction parameters. The optimal conditions were as follows: 60 % ethanol solution as the extract solvent, material-liquid ratio of 1:25, pH value of 4, enzyme addition amount of 1.5 %, enzymatic hydrolysis time of 30 min, enzymatic hydrolysis temperature of 40 ℃, and ultrasonic time of 50 min. Comparing the total flavonoid yield of VF and processed VF (PVF) extracted using different methods, it was observed that UAE resulted in a higher total flavonoid yield compared to traditional ultrasound extraction and enzyme extraction. Additionally, the total flavonoid yield of PVF extracted by all three methods was generally higher than that of VF. The PVF solution extracted by UAE also demonstrated better in vitro antioxidant activity compared to VF. These results suggest that UAE is an effective method to enhance the activity of natural total flavonoids. The study of the physicochemical properties and in vitro antioxidant activity of VF and PVF showed that the total flavonoid yield and antioxidant activity significantly increased after VF stir-frying, indicating that their efficacy can also be enhanced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Passiflora cincinnata is a Passifloraceae typical of the Caatinga, a biome unique to Brazil. It has various pharmacological properties associated with its high flavonoid content. Vitexin, isovitexin, orientin, isoorientin and derivatives are the main chemical and pharmacological markers for this plant. Although flavonoids enriched-extracts have been widely applied in phytocosmetics, especially in sunscreen formulations, the use of P. cincinnata as a photoprotective ingredient remains unexplored. Different hydro-alcoholic extracts were prepared and their antioxidant and photoprotective activities were evaluated by in vitro assays. The most promising extract (Pc-1) was analyzed by HPLC-DAD-ESI-MS/MS. Nine flavonoids were identified as major compounds: isovitexin-7-O-glucoside, isoorientin-2"O-hexoside, orientin, isoorientin, isovitexin-2"-O-glucoside, isovitexin-6"-O-glucoside, isoscoparin and isoquercitrin. Finally, Pc-1 (5 and 10 %, v/v) was incorporated into gel formulations, alone or combined to commercial chemical filters (benzophenone-3 and octyl methoxycinnamate). Formulations containing Pc-1 showed high SPF spectrophotometric values. When combined to commercial filters, Pc-1 (5 %) potentiated their photoprotective efficacy (p<0.05). A physicochemical characterization indicated no incompatibility or signs of instability after extract incorporation. Altogether, these findings encourage the use of Pc-1 as a photoprotective ingredient or co-adjuvant in sunscreens formulations., (© 2024 The Author(s). Chemistry & Biodiversity published by Wiley-VHCA AG.)

The phytochemical investigation of both chloroform and ethyl acetate extracts of Genista lobelii DC from an Algerian endemic plant led to the isolation of a new isoflavonoid Aspalathoidin compound ( 1 ) and nine known compounds (laburnetin, isokaempferide, retamasin B, ephedrodin, sakuretin, isoprunetin, genistein -7- O -β-glucoside, derrone-4'- O -methyl ether and eriodictyol-7,3'-dimethylether). Twelve phenolic compounds were identified in ethyl acetate and n -butanol extracts through a qualitative investigation of phenolic compounds using HPLC. Finally, both extracts were estimated for their phenolic and flavonoid contents as well as the evaluation of their antioxidant activity using five different assays DPPH, CUPRAC, ABTS, GOR and the sun protection factor SPF was determined as an index of the photoprotective capacity of the G.lobelii DC extracts. The extract of chloroform and ethyl acetate has good antioxidant and includes significant levels of phenolic and flavonoid components.

This comprehensive analysis of the fruits of Rosa spp. (FR) evaluates their chemical components and antioxidant activity. The study quantified total flavonoids and polyphenols using aluminum trichloride colorimetric assay and Folin-Ciocalteu methods, with the fruit of Rosa. laxa Rtez. var. mollis Yü et Ku. sample exhibiting the highest concentrations of 59.21 mg/g and 81.13 mg/g, respectively. Ultra-High-Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry (UPLC-TQ-MS) assessed seven primary components, with notable levels of euscaphic acid, ursolic acid, and gallic acid. Antioxidant activities were tested using DPPH and ABTS methods, showing strong activities in samples the fruits of Rosa. persica Mickx ex Juss. and Rosa. laxa Rtez. var. kaschgarica (Rupr.) Y. L. Han. Chemometric analyses, including similarity, cluster, principal component, and grey relational analyses, were used to explore relationships between FR varieties and their antioxidant properties. The study provides a vital basis for future FR quality assessments., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Banisteriopsis (Malpighiaceae) is an important genus of neotropical savannas with related biological and medicinal activities but under-explored metabolomic profiles. We present a chemometric analysis for discriminating secondary metabolites of three species of Banisteriopsis (B. laevifolia, B. malifolia, and B. stellaris) leaves. Initially, each species was separately extracted with ethanol:water (4 : 1, v/v) and analysed by Ultra Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS/MS). The chromatographic profiles were subjected to Global Natural Product Social (GNPS) and Partial Least Squares Discriminant Analysis (PLS-DA). Eighty-nine compounds (cosine≥0.90) were annotated, including flavonoids, phenolics, and acids. The chemometric analysis (VIP Score) showed each species' relative concentration of the more relevant compounds. In addition, four compounds that discriminate the metabolomic profiles of B. laevifolia, B. malifolia, and B. stellaris were identified by PLS-DA., (© 2024 Crown copyright and The Author(s). Chemistry & Biodiversity published by Wiley-VHCA AG. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.)

Background: Evaluation of herbicidal activity and identification of active compounds are important bases for the development of new botanical herbicides., Results: This study confirmed that Symphoricarpos orbiculatus has high herbicidal activities against mono-dicotyledonous weeds, including Echinochloa crusgalli, Digitaria sanguinalis, Amaranthus retroflexus and Portulaca oleracea. By bioassay-guided isolation, 12 compounds were isolated and identified from S. orbiculatus for the first time, including iridoids: naucledal (K1), loganin (K2), loganigenin (K3), loganin acid (K4), glucologanin (K5) and vogeloside (K6), as well as flavonoids: quercetine (K7), luteolin (K8), nobiletin (K9), astragalin (K10), isorhamnetin 3-d-glucoside (K11) and rutin (K12). Biological assays showed that iridoids are the main active ingredients of S. orbiculatus. The compounds of K5 and K6 could inhibit both the root (IC 50  = 37.54 and 38.91 μg mL -1 , respectively) and shoot (IC 50  = 42.78 and 45.72 μg mL -1 , respectively) of Portulaca oleracea, which have a weeding toxicity similar to that of the commercialized plant-based herbicide pelargonic acid. In addition, the results of pot culture assay showed that S. orbiculatus ethanol extracts had high fresh weight control effect against Digitaria sanguinalis and P. oleracea at the concentration of 40 g L -1 . After 7 days, both the soil treatment and the stem and leaf spray method resulted in severe leaf necrosis and significant leaf etiolation., Conclusion: Symphoricarpos orbiculatus and its herbicidal active compounds have the potential to develop into botanical herbicides, and are first reported in the present study. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Three new flavan derivatives including two methylene-linked flavan-3-ol dimers, bis(8-epiafzelechinyl)methane (1), and 8,8-(epiafzelechin-afzelechin)methane (2), a flavan-3-ol monomer, (-)-3-O-acetyl-epiafzelechin (3) and four known related compounds (4-7) were isolated from the leaves and stems of Cassia nodosa. Their structures were elucidated by extensive spectroscopic analyses and CD data. The isolates were evaluated for their antioxidant, α-glucosidase inhibitory, cytotoxic and neuroinflammatory activities, and compound 3 exhibited remarkable radical scavenging activities in both the DPPH and ABTS models with IC 50 values of 2.65±1.25, and 4.78±0.91 μg/mL, respectively., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Tilianin and linarin, two rare glycosylated flavonoids in the aromatic endangered medicinal plant Nardostachys jatamansi (D.on)DC., play an important role in the fields of medicine, cosmetics, food and dye industries. However, there remains a lack of comprehensive understanding regarding their biosynthetic pathway. In this study, the phytochemical investigation of N. jatamansi resulted in the isolation of linarin. With help of AlphaFold2 to cluster the entire glycosyltransferase family based on predicted structure similarities, we successfully identified a flavonoid glycosyltransferase NjUGT73B1, which could efficiently catalyze the glucosylation of acacetin at 7-OH to produce tilianin, also the key precursor in the biosynthesis of linarin. Additionally, NjUGT73B1 displayed a high degree of substrate promiscuity, enabling glucosylation at 7-OH of many flavonoids. Molecular modeling and site-directed mutagenesis revealed that H19, H21, H370, F126, and F127 play the crucial roles in the glycosylation ability of NjUGT73B1. Notably, comparation with the wild NjUGT73B1, mutant H19K led to a 50% increase in the activity of producing tilianin from acacetin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

After myocardial ischemia/reperfusion injury (MI/RI), endothelial cell injury causes impaired angiogenesis and obstruction of microcirculation, resulting in an inflammatory outburst that exacerbates the damage. Therefore, synergistic blood vessel repair and inflammation inhibition are effective therapeutic strategies. In this study, we developed a platelet membrane (PM)-encapsulated baicalin nanocrystalline (BA NC) nanoplatform with a high drug load, BA NC@PM, which co-target to endothelial cells and macrophages through the transmembrane proteins of the PM to promote angiogenesis and achieve anti-inflammatory effects. In vitro cell scratch assays and transwell assay manifested that BA NC@PM could promote endothelial cell migration, as well as increase mRNA expression of CD31 and VEGF in the heart after treatment of MI/RI mice, suggesting its favorable vascular repair function. In addition, the preparation significantly reduced the expression of pro-inflammatory factors and increased the expression of anti-inflammatory factors in plasma, promoting the polarization of macrophages. Our study highlights a strategy for enhancing the treatment of MI/RI by promoting angiogenesis and regulating macrophage polarization via the biomimetic BA NC@PM nanoplatform., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The antioxidant activity of Ginkgo biloba leaf (GBL) extract is closely related to its efficacy against various diseases; however, the antioxidant activities of the specific constituents of GBL remain unclear. In this study, 194 GBL constituents were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, including 97 flavonoids, 37 terpenoids, 29 lignans, 19 carboxylic acids, 5 alkylphenolic acids, 5 alkylphenols, and 2 other compounds. The cleavage rules of the main constituents of GBL were dissected in detail. The 36 GBL constituents with high antioxidant activity were subsequently discovered using the oxygen radical absorbance capacity assay, including 30 flavonoids and six carboxylic acids. Finally, an HPLC analysis method was established to determine the content of the nine major antioxidants in the three batches of GBL. Among them, kaempferol 3-O-β-D-(6″-p-coumaroyl) glucopyranosyl-(1-2)-α-L-rhamnopyranoside, kaempferol-3-O-rutinoside, and rutin exhibited high antioxidant activity and were found in significant amounts in GBL, with concentrations greater than 0.7 mg/g. These results provide an important reference for the development of pharmaceuticals and health products containing GBL., (© 2024 John Wiley & Sons Ltd.)

Three new flavonoids including two isoflavanones sophortones A and B ( 1 and 2 ), and one chalcone sophortone C ( 3 ) were isolated from the roots of Sophora tonkinensis . Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Almost half of all medicines approved by the U.S. Food and Drug Administration have been found to be developed based on inspiration from natural products (NPs). Here, we report a novel strategy of scaffold overlaying of scaffold-hopped analogs of bioactive flavones and isoflavones and installation of drug-privileged motifs, which has led to discovery of anticancer agents that surpass the functional efficiency of the original NPs. The analogs, 2,3-diaryl-pyridopyrimidin-4-imine/ones were efficiently synthesized by an approach of a nitrile-stabilized quaternary ammonium ylide as masked synthon and Pd-catalyzed activation-arylation methods. Compared to the NPs, these NP-analogs exhibited differentiated functions; dual inhibition of human topoisomerase-II (hTopo-II) enzyme and tubulin polymerization, and pronounced antiproliferative effect against various cancer cell lines, including numerous drug-resistant cancer cells. The most active compound 5l displayed significant inhibition of migration ability of cancer cells and blocked G1/S phase transition in cell cycle. Compound 5l caused pronounced effect in expression patterns of various key cell cycle regulatory proteins; up-regulation of apoptotic proteins, Bax, Caspase 3 and p53, and down-regulation of apoptosis-inhibiting proteins, BcL-xL, Cyclin D1, Cyclin E1 and NF-κB, which indicates high efficiency of the molecule 5l in apoptosis-signal axis interfering potential. Cheminformatics analysis revealed that 2,3-diaryl-pyridopyrimidin-4-imine/ones occupy a distinctive drug-relevant chemical space that is seldom represented by natural products and good physicochemical, ADMET and pharmacokinetic-relevant profile. Together, the anticancer potential of the investigated analogs was found to be much more efficient compared to the original natural products and two anticancer drugs, Etoposide (hTopo-II inhibitor) and 5-Flurouracile (5-FU)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Sankar K. Guchhait reports financial support was provided by Science and Engineering Research Board. Prof. Chanakya Nath Kundu reports financial support was provided by Indian Council of Medical Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Radix gentianae (RG) is a traditional Chinese medicine used for the treatment of acute and chronic hepatitis in clinic. However, the chemical profile of RG is still unconfirmed, which hindered the progress of pharmacological study and clinical application. In this study, ultra-high performance liquid chromatography together with quadrupole time-of-flight mass spectrometry techniques were employed to separate and characterize the chemical constituents in RG. Under the optimized conditions, a total of 60 compounds were rapidly identified or tentatively characterized. Results indicated that iridoid glucosides, flavonoids, organic acids, amino acids, saccharides and nucleosides were major constituents in RG. It is concluded the established method can help to clarify the substance basis and provide useful information for ascertaining the bioactive constituents and action mechanism of RG., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Lactobacillus strains have emerged as promising probiotics for enhancing the bioactivities of plant-based foods associated with flavonoid biotransformation. Employing microbial fermentation and mass spectrometry, we explored flavonoid metabolism in lychee pulp fermented separately by Lactiplantibacillus plantarum and Limosilactobacillus fermentum. Two novel metabolites, 3,5,7-trihydroxychromone and catechol, were exclusively identified in L. plantarum-fermented pulp. Concomitant with consumption of catechin and quercetin glycosides, dihydroquercetin glycosides, 2,4-dihydroxybenzoic acid and p-hydroxyphenyllactic acid were synthesized by two strains through hydrogenation and fission of C-ring. Quantitative analysis revealed that bound phenolics were primarily located in water-insoluble polysaccharides in lychee pulp. Quercetin 3-O-rutinoside was partially liberated from water-insoluble polysaccharides and migrated to water-soluble polysaccharides during fermentation. Meanwhile, substantial accumulations in short-chain fatty acids (increased 1.45 to 3.08-fold) and viable strains (increased by 1.97 to 2.00 Log 10 CFU/mL) were observed in fermentative pulp. These findings provide broader insight into microbial biotransformation of phenolics and possible guidance for personalized nutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The antioxidant and antiglycation activities of the Ficus leaf extracts were evaluated using in vitro assays. The antioxidant activity was determined using the α, α-diphenyl-β-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays. In vitro ferric reducing activity was evaluated using the ferric reducing antioxidant power assay. The antiglycation potential of the extract was evaluated using dinitrophenylhydrazine, thiobarbituric acid and protein thiol assays. The inhibition of the formation of advanced glycation end products (AGEs) was detected using AGE-specific fluorescence with a fluorescence spectrophotometer. This study was aimed at investigating the potential of Ficus palmata Forssk. leaf extracts, which have abundant bioactive constituents, including polyphenols and flavonoids, in inhibiting glycation and cancer. The results show that the aqueous and methanolic Ficus leaf extracts are rich in phenolic and flavonoid compounds. Both extracts showed potent antioxidant activities. Furthermore, the methanolic extract showed antiglycation activities, as assessed using an in vitro model of bovine serum albumin glycation with D-ribose. The polyphenol- and flavonoid-rich Ficus leaf extracts exhibit antiglycation, chemopreventive and antioxidant activities and have potential for use in the treatment of diseases, such as cancer, which involve oxidative and glycative impairment of cellular proteins.

A new coumarin ( 1 ) and a new flavonoid ( 2 ) were isolated from the air-dried flower buds of Ochrocarpus longifolius , together with ten known compounds ( 3 - 12 ). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Qizhi Xiangfu Pills (QZXFPs) is one of the most commonly used traditional Chinese medicine preparations for the treatment of dysmenorrhea, but the existing quality evaluation standards have certain shortcomings and deficiencies. An effective and scientific quality evaluation method plays a vital role in medication safety. In this study, fingerprint combined with chemometric analysis and quantitative analysis of multi-components by a single marker (QAMS) method was used to comprehensively evaluate the quality of QZXFPs. The fingerprints of 28 batches samples were established and 23 common peaks were distinguished, of which 7 peaks were identified as albiflorin, paeoniflorin, baicalin, ligustilide, cyperotundone, nootkatone and α-cyperone. The content of these seven active ingredients was determined simultaneously by the QAMS method and there was no significantly different between QAMS and the external standard method. Additionally, similarity analysis, hierarchical cluster analysis, principal component analysis and orthogonal partial least squares discrimination analysis were applied for classifying the 28 batches of samples, and to find the main components causing the quality differences between different batches. In conclusion, the established method can comprehensively evaluate the consistency of quality between different batches and provide a reference for formulation quality evaluation to ensure safe and effective application of QZXFPs., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A new triterpene saponin, 2, 3, 21, 23-tetrahydroxyolean-12-en-28-oic-acid-28- O -β-D- glucosyl-(2''→1')-β-D-glucoside ( 1 ), was isolated from the n -butanol extract of dried aerial parts of Salvia argentea L. (Lamiaceae) in addition to two known flavonoids, apigenin 7- O -β-D-glucoside ( 2 ), threo-guaiacylglycerol 3- O -[6- O - p -hydroxybenzoyl]-β-D-glucoside ( 3 ), luteolin 7- O -β-D-glucoside ( 4 ), verbascoside ( 5 ) and rosmarinic acid ( 6 ). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D-, 2D-NMR and HR-ESI-MS techniques and by comparing their NMR data with those reported in the literature. Compound 6 exhibited the highest antioxidant activity in DPPH assay (IC 50 <3.00 µg/mL) which was better than the standards BHA, BHT, Trolox and ascorbic acid.

Anxiety and epilepsy are common worldwide and represent a primary global health concern. Fisetin, a flavonoid isolated from Bauhinia pentandra, has a wide range of biological activities may be a promising alternative to combat diseases related to the central nervous system (CNS). The present study aimed to investigate the anxiolytic and anticonvulsant effects of fisetin on adult zebrafish. Furthermore, molecular docking simulations were performed to improve the results. Fisetin did not present toxicity and caused anxiolytic behavior and delayed seizures in animals. This effect may occur through serotonin neurotransmission at 5-HT 3A and/or 5-HT 3B receptors. Molecular docking simulations showed that fisetin interacts with the orthosteric site of the 5-HT 3A receptor with strong H-bond interactions with the Trp156 residue, with a strong contribution from the catechol ring, a behavior similar to that of the antagonist co-crystallized inhibitor granisetron (CWB). Fisetin may be a promising alternative to combat diseases related to the central nervous system., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Asparagus racemosus Linn. is an ethnopharmacologically important plant having extensive uses in Ayurveda, Unani, and Siddha. This study was carried out to evaluate the chemical profile of A. racemosus Linn. using GC-MS and FT-IR analysis, and its polyphenol content and antioxidant effects. Plants were collected from Bhujiyaghat, Nainital (29.3159° N, 79.5245° E) in Kumaun Himalayas. GC-MS with FT-IR analysis identified multiple functional groups, including carboxylic acid derivatives. Methyl 11, 12-octadecadienoate, was screened as the major compounds by GC-MS. A. racemosus contains a high concentration of phenols (80.92 ± 0.57 mg of GAE/g of DW), flavonoids (58.22 ± 1.62 mg of QE/g of DW), and tannins (86.77 ± 0.81 mg of TAE/g of DW). DPPH (24.63 ± 0.21 g/ml) and FRAP (72.49483 ± 0.130549 mg of AAE/g of DW) assays revealed the presence of significant antioxidant activity in A. racemosus .

The n -butanol extract of Stachys arvensis (L.) L. aerial parts (BESA) was analysed by LC-HRMS/MS. 43 Polyphenols, including flavonoids, cinnamic acid derivatives, phenylethaoids, chromones, gallotannins, coumarins and chalcones with hyperoside (13.85%), panasenoside (10.31%), myricitrin (7.89%) and sayaendoside (7.16%), as the major compounds, were identified. High total phenolics (470.21 ± 1.22 mg GAE/g extract) and total flavonoids (189.05 ± 0.72 mg QE/g extract) contents were measured. In addition, the BESA exhibited a higher antioxidant effect in CUPRAC (A 0.5 :0.45 ± 0.03 μg/mL), DPPH (IC 50 :4.51 ± 0.16 μg/mL) and ABTS (IC 50 :7.10 ± 0.18 μg/mL) assays than the standards BHA and α-Tocopherol. Moreover the extract showed a good inhibitory effect against BChE (IC 50 : 145.02 ± 0.03 μg/mL) and α-amylase (IC 50 :2.66 ± 0.0024 mg/mL). The BESA exhibited an excellent anti-inflammatory activity (IC 50 :416 ± 0,056 μg/mL) which was close to that of acetylsalicylic acid, used as a control. The BESA was toxic towards T. molitor larvae and it possessed a good antibacterial activity against gram (+) and gram (-) tested strains.

The p53 Y220C is one of the most frequently observed structural mutants in various human cancers. The substitution of residue Tyr to Cys makes the p53 DNA binding domain susceptible to solvent entry into the hydrophobic core of the domain thereby destabilizing p53, which results in loss of its tumor suppressor activity. The mutation creates a structural crevice at the region between S3/S4 and S7/S8 loops in the DNA binding domain which can be targeted by small molecules. Studies have shown that the synthetic and natural compounds could bind to this crevice and restore the structure and function of the mutant p53Y220C to the wild type. In our previous study, we have shown Curcumin could rescue the function of mutant p53Y220C in pancreatic cancer cell line BxPC-3 harboring genomic mutation. In this study, we explored six flavonoids structurally similar to Curcumin such as Apigenin, Isoliquiritigenin, Liquiritigenin, Luteolin, Methylophiopogonanone A (MPA), and Methylophiopogonanone B (MPB) to test their potency to restore p53Y220C by molecular docking, molecular dynamics simulations and cytotoxicity assay. The secondary structure analysis after the MD simulations suggested that these compounds could stabilize the mutant p53 DNA binding domain to the wild type. In the cell-based cytotoxicity studies using p53Y220C harbouring BxPC-3 cell lines, the compounds MPA and MPB showed 75% cell death at 100 µM concentration. We proposed that the flavonoids MPA and MPB have the therapeutic potential to restore p53Y220C and could be used as a combinatorial therapy to reduce the dosage burden.Communicated by Ramaswamy H. Sarma.

Round green tea (RGT) presents unique properties and is widely distributed in China, and during processing, it undergoes dynamic changes in non-volatile metabolites (NVMs), which are poorly understood. Utilizing UHPLC-Q-Exactive/MS analysis, this study comprehensively characterized 216 NVMs during RGT processing and identified fixation and pan-frying as key processes influencing NVMs. Additionally, 23 key differential NVMs were screened, with amino acid and flavonoid metabolism highlighted as key metabolic pathways for RGT taste and color quality. The impact of pan-frying degree on shape, color, and taste was also explored. Moderate pan-frying led to optimal results, including a tight and round shape, green and bright color, mellow and umami taste, and reduced astringent and bitter taste NVMs, including epigallocatechin gallate, procyanidin B2, myricetin 3-O-galactoside, quinic acid, strictinin, phenylalanine, and theobromine. This study addresses the NVM research gap in RGT processing, thus providing a technical foundation for the precision-oriented processing of high-quality tea., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rice (Oryza sativa L.) husk harbors a substantial proportion of biological metabolites, as one of the most plentiful agriculture by-products in rice milling process, rice husk remains poorly utilized. As a continuing search for potential bioactive molecules from the husk of rice, a totally of twelve components (1-12), including six sterol ferulates (1-6), one flavonoid (7), one dipeptide (8), and four phenylpropanoid derivatives (9-12) were obtained. All the chemical structures were elucidated based on comprehensive spectroscopic data. Wherein, compounds 1 and 2 were yield as previous undescribed metabolites, and the comprehensive NMR data for compounds 3 and 4 were first presented in its entirety. Motivated by the similarity of the structural motifs of components 1-6 to that of reported sterol ferulates, the antioxidant and anti-inflammatory effects for compounds 1-6 were evaluated in vitro. Among them, compounds 5/6 had a significant antioxidant activity compare to that of vitamin E in both DPPH and reducing power assay up to the concentration 40 μg/ml; while compounds 1 and 2 exhibited weak suppressive effect on the production of nitric oxide, with the IC 50 values of 53.27±1.37 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Blueberry leaves (BBL) are a natural source with strong antioxidant activity, but bioactive compounds and their seasonal variation remain vague. Here, two major classes of compounds including four caffeoylquinic acids and eight flavonoids were identified in two southern highbush cultivars ("Lanmei" #1 and "Jewel") grown in China. Major bioactive compounds were discovered using an online HPLC post-column derivatization system and determined as neochlorogenic acid (NeoCA), chlorogenic acid (CA), rutin, hyperoside, and isoquercitrin. CA contributed the most to the BBL antioxidant activity. "Lanmei" showed significant advantages in terms of rutin content and antioxidant activity over "Jewel" (P < 0.05). The highest CA content (CAC) of juvenile "Jewel" leaves reached 17.9%. July was the optimum harvest time for both cultivars after fruiting stage. Total phenolic content (TPC) and Trolox equivalent antioxidant capacity (TEAC) of fresh BBL were accurately predicted by a portable near-infrared (NIR) device in a rapid, low-cost, and non-destructive way in situ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The effects of dynamic high-pressure microfluidization (DHPM) treatment on the rheological properties, multiscale structure and in vitro digestibility of complex of maize starch (MS), konjac glucomannan (KGM), and bamboo leaf flavonoids (BLFs) were investigated. Compared with MS, the MS-KGM-BLF complex exhibited reduced viscosity and crystallinity, along with increased lamellar thickness to 10.26 nm. MS-KGM-BLF complex had lower viscosity after DHPM treatment. The highest ordered structure and crystallinity were observed at 50 MPa, with the α value increasing from 3.40 to 3.59 and the d value decreasing from 10.26 to 9.81 nm. However, higher DHPM pressures resulted in a decrease in the α value and an increase in the d value. The highest gelatinization enthalpy and resistant starch content were achieved at 100 MPa DHPM, while the fractal structure shifted from surface fractal to mass fractal at 150 MPa. This study presents an innovative method for enhancing the properties of MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Achieving rapid, cost effective, and intelligent identification and quantification of flavonoids is challenging. For fast and uncomplicated flavonoid determination, a sensing platform of smartphone-coupled colorimetric sensor arrays (electronic noses) was developed, relying on the differential competitive inhibition of hesperidin, nobiletin, and tangeretin on the oxidation reactions of nanozymes with a 3,3',5,5'-tetramethylbenzidine substrate. First, density functional theory calculations predicted the enhanced peroxidase-like activities of CeO 2 nanozymes after doping with Mn, Co, and Fe, which was then confirmed by experiments. The self-designed mobile application, Quick Viewer, enabled a rapid evaluation of the red, green, and blue values of colorimetric images using a multi-hole parallel acquisition strategy. The sensor array based on three channels of CeMn, CeFe, and CeCo was able to discriminate between different flavonoids from various categories, concentrations, mixtures, and the various storage durations of flavonoid-rich Citri Reticulatae Pericarpium through a linear discriminant analysis. Furthermore, the integration of a "segmentation-extraction-regression" deep learning algorithm enabled single-hole images to be obtained by segmenting from a 3 × 4 sensing array to augment the featured information of array images. The MobileNetV3-small neural network was trained on 37,488 single-well images and achieved an excellent predictive capability for flavonoid concentrations (R 2  = 0.97). Finally, MobileNetV3-small was integrated into a smartphone as an application (Intelligent Analysis Master), to achieve the one-click output of three concentrations. This study developed an innovative approach for the qualitative and simultaneous multi-ingredient quantitative analysis of flavonoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)