Search

Huang long bing (HLB) infection of oranges induces the biosynthesis and accumulation of bitter limonoids. The objective of this study was to debitter HLB-affected orange juice while preserving the tasteless and health-promoting limonoid glucoside and flavanones using resin adsorption. Three resins (FPX66, PAD900, and XAD16N) were found to have higher adsorption and desorption capacity for limonin among seven selected resins. Adsorption of limonoids rapidly increased in the first 2 h of kinetic tests, while slower adsorption kinetics were observed for flavanones. Limonin isothermal adsorption fit best with the Langmuir model, suggesting a physical, monolayer process. Dynamic adsorption showed that a fixed-bed column packed with PAD900 was able to debitter 200 bed volumes of orange juice before limonin reached its taste threshold of 4.7 µg/mL in the eluent. The resin was regenerated by eluting the column with four bed volumes of alcohol or 4% NaOH to remove adsorbed compounds from the resin. Resin adsorption reduced limonin content in orange juice from 5.85 to 1.34 µg/mL but also decreased tasteless compounds by at least 40%. A consumer sensory test gave the debittered juice a higher overall liking and preference over untreated juice. This study showed that resin adsorption is an effective approach to reduce the bitterness of orange juice affected by HLB., (© 2025 Institute of Food Technologists.)

Drying is the primary processing step in Exocarpium citri grandis (ECG), yet its quality changes throughout the drying process have not been elucidated. Dynamic changes of drying behavior, structure, color, active components, antioxidant properties, and volatile oil in ECG under different drying temperatures (50, 60, 70, and 80°C) were investigated, and the quality change mechanism was revealed. Results showed that the moisture ratio decreased rapidly and that structural damage occurred as moisture content decreased from 1.0000 to 0.2175 g/g (on a dry basis, d.b.), which accelerated flavonoids, polysaccharides, volatile oil, and antioxidant activity degradation, whereas levels of naringin and rhoifolin were increased. The above quality change process was accelerated with the increasing temperature. Correlation analysis revealed that active components had a synergistic effect on antioxidant activity, and the total color difference (ΔE) value and that active components could be well fitted by a linear mathematical model with correlation coefficient (R 2 ) of 0.7749-0.9781. Moreover, all the indicators were uniformly quantified using comprehensive evaluation method to obtain a comprehensive score, which was the highest (0.57) at 70°C, with high drying efficiency, well quality, and low energy consumption. The biosynthesis pathway verified that the species of volatile oil components increased, including newly terpenes, alcohols, aldehydes, esters, and others after 0.2175 g/g. This study revealed that the total content of active components in ECG decreased before 0.2175 g/g, and then the metabolite content and species increased during drying, as well as obtained the optimal drying temperature (70°C)., (© 2025 Institute of Food Technologists.)

As a traditional Chinese medicine, Sanao decoction (SAD) has been used to treat chronic obstructive pulmonary disease (COPD) for multi-years. However, the potential mechanism and targets for its effects of SAD remain unknown. The 94 components of SAD were identified by UPLC-LTQ-Orbitrap MS. Meanwhile, the quantitative analysis of multi-components by single marker (QAMS) method was used to control the quality of SAD, including ephedrine hydrochloride, amygdalin, liquiritin, liquiritigenin, glycyrrhizic acid and glycyrrhetinic acid. The method was strictly validated with recovery (90.0-110.0%), precision [relative standard deviation (RSD), 0.79-2.01%], stability (RSD, 1.84-2.64%), repeatability (RSD, 0.45-3.03%) and relative correction factors (RSD, 0.28-2.67%), respectively. All the compounds showed good linearities (R2 > 0.999). Subsequently, 37 target proteins of SAD in the treatment of COPD were screened. The "Compounds-Targets" interaction and protein-protein interaction network found that TNF-α, IL-6 and VEGFA may act a crucial role in the treatment of COPD by SAD. Molecular docking demonstrated that TNF-α had good affinity with the main components of SAD. A strategy of QAMS and network pharmacology was a novel method to assess the quality control of SAD and uncover the targets and potential mechanism of SAD in the treatment of COPD., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: European aspen (Populus tremula L.) knotwood contains large amounts of polyphenolic metabolites, mainly flavonoids, and can be considered as a promising industrial-scale source of valuable bioactive compounds. Valorization of knotwood extractives requires detailed information on their chemical composition and a relevant analytical methodology., Objective: This study proposes combined analytical strategy for non-targeted screening and identification of polyphenolic plant metabolites and is aimed at comprehensive characterization of knotwood extractives., Materials and Methods: Aspen knotwood acetone extract with determined antioxidant activity was an object of the study. Two-dimensional NMR spectroscopy with Structure Elucidator expert system was used for preliminary search of major components and specific structures. Liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) with data-dependent MS/MS spectra acquisition was used as a complementary technique providing molecular-level characterization and identification of the detected metabolites., Results: Twenty-eight phenolic metabolites were found and identified. Among them, flavonoids, aromadendrin and naringenin, as well as their glycosylated derivatives (mainly O-glucosides) and methyl ethers, dominated. Taxifolin and its 7-O-glucoside were detected as minor components. Other detected compounds are represented by p-coumaric acid and its rutinoside and small amounts of glycosylated ferulic acid. Nineteen of the detected compounds were discovered in aspen knotwood for the first time. The results were confirmed by preparative isolation of individual compounds and NMR studies., Conclusion: The proposed analytical strategy based on 2D NMR and HPLC-HRMS can be considered a powerful tool in the analysis of plant extractives and allowed for the identification and semi-quantification of a large number of polyphenols in aspen knotwood., (© 2024 John Wiley & Sons Ltd.)

The rapeseed meal, a type of residual by-product of rapeseed oil production was used as the precursor to prepare nitrogen self-doping carbon dots RM-CDs through an easy hydrothermal process. Thanks to the introduction of nitrogen element and oxygen-containing functional groups, RM-CDs had a fluorescence quantum yield of 18.6 %. The RM-CDs demonstrated highly stable to the ionic strength, pH, and ultraviolet radiation. However, their bright blue fluorescence was significantly weakened by baicalein owing to the inner-filter effect and static quenching effect. As a result, RM-CDs could be used as the fluorescent sensing materials for baicalein detection with a wide range of linear response (0.5-170 μM) as well as low limit of detection (0.046 μM). Moreover, the as-developed sensing platform was also applicable to detect baicalein in actual samples. The developed RM-CDs was sustainably prepared from the biomass by-product of rapeseed meal, this approach expanded the application scopes of CDs., 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.)

Developing an accurate and ultrasensitive method for the simultaneous detection of baicalin and baicalein, two key flavonoid from Scutellaria baicalensis, is critical, particularly in the context of traditional Chinese medicine. This study focuses on an innovative electrochemical approach, utilizing a biochar (BC)/ZIF-67/MnCo 2 O 4 composite, which was fabricated via a combination of ultrasonic, calcination, and hydrothermal treatments. The resulting BC/ZIF-67/MnCo 2 O 4 electrode exhibits exceptional sensitivity, with linear response ranges of 0.01 μM-400 μM. The limits of detection (LOD) for baicalein and baicalin were as low as 0.056 nM and 0.49 nM, respectively. The practical evaluations in serum and Scutellaria baicalensis demonstrate high recovery rates of 93.65 %-95.25 % for baicalein and 98.23 %-101.52 % for baicalin, with relative standard deviations below 3.99 % and 2.92 %, respectively. This study not only presents a promising technique for quality control in traditional Chinese medicine but also expands the potential applications of BC/ZIF-67/MnCo 2 O 4 composites in electrochemical sensing, paving the way for applications in food safety monitoring and herbal medicine standardization., 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 quality control of herbal medicines is key to their clinical efficacy. The multi-component and multi-effect characteristics of herbal medicines have prompted scholars to clarify various factors related to quality evaluation through various methods. Nevertheless, the relationship between chemical properties and their associated clinical efficacy is little reflected in the quality control techniques currently in use. To address the issue, a novel herbal quality standard system based on the efficacy-oriented Q-marker of the effect-constituent index (ECI) is promoted in this study, using Scutellariae Radix (SR), a widely used herbal medicine with anti-inflammation, anti-tumor, anti-viral and other therapeutic effects, as a case study. Combined with chromatographic analysis and bioassay, four Q-markers including baicalin, baicalein, wogonin and oroxylin A were selected based on the anti-inflammatory efficacy of SR. The ECI model of SR was constructed by combining the content determination of the Q-markers via ultra-high-performance liquid chromatography-triple quadrupole mass spectroscopy (UHPLC-QqQ-MS/MS) with the corresponding biological potency obtained from the anti-inflammatory effects on tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. Correlation analysis showed that the ECI was significantly correlated with the measured anti-inflammatory activity ( p < 0.01). The ECI exhibited a good ability to determine and predict the bioeffect-based quality grade for SR. Overall, the construction and application of the ECI for SR in this study provides a beneficial reference for quality evaluation methods of other herbs with distinct effects and active ingredients.

Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are distinct herbs outlined by the Chinese Pharmacopoeia. They are sourced from the same plant but harvested at different times, resulting in differences in efficacy. It is important to avoid mixing them clinically and to distinguish between the two. Furthermore, dissimilar cultivation conditions may cause variability in the quality of herbs, so it is vital to differentiate drugs from dissimilar origins. In this study, two plants, AF and AFI from different provinces, were comparatively analyzed based on High Performance Liquid Chromatography (HPLC) fingerprints and classified using chemometric methods. The results indicate that the two medicines can be clearly distinguished. Also, AF and AFI grown in different locations can be distinguished. Ten chemical markers were screened, and their variations were determined, including eriocitrin, narirutin, naringin, meranzin hydrate, naringenin, hesperidin, nobiletin, tangeretin, neohesperidin, and poncirin. Subsequent network pharmacology correlated the screened chemical components with the biological network of the organism. The material basis of the difference in efficacy of the two homologous herbs was explored from the perspective of changes in chemical composition. This study provides a reference for formulating quality evaluation standards for AF and AFI and lays a foundation for the efficacy-related quality research of the two.

Thirteen flavanone racemates were successfully separated using a Chiralpak® IA column and isopropanol-hexane (50:50, v/v). The mobile phase flow rate and detection wavelength were 0.5 mL/min and 254 nm. The retention times values ranged from 5.50 and 56.45 min. The values of the retention, separation, and resolution factors ranged from 0.63 to 21.67, 1.12 to 2.45, and 0.13 to 11.94. The docking binding energies ranged from -6.2 to -8.2 kcal/mol, showing enthalpy-determined host-guest complex formation. The molecular docking results and the experimental data were agreed well. The results showed that S-enantiomers had stronger bindings with chiral selectors compared to R-enantiomers. Consequently, the R-enantiomers eluted first followed by S-enantiomers. The reported method is highly useful to determine the enantiomeric composition of the reported flavanone in any sample., (© 2024 John Wiley & Sons Ltd.)

A Magnetic Molecularly Imprinted Polymer (MMIP) was developed using naringin as template molecule, acrylamide as functional monomer and polymerized by ultrasound irradiation for the adsorption of naringin. In an unexpected turn of results, the selectivity study unveiled that the synthesized MMIP exhibited a higher affinity for quercetin over naringin. Given this high selectivity, adsorption isotherm and kinetic studies were conducted for both quercetin and naringin. The adsorption isotherm indicated multilayer adsorption of the adsorbate on the adsorbent. The kinetic study showed better agreement with the pseudo-second-order kinetic model. The maximum adsorption capacity of 7.2 mg/g was achieved for quercetin at 50 mg/L and 4.9 mg/g was attained for naringin at the same concentration. Furthermore, quercetin quantification was performed by coupling MMIP with HPLC-UV, with method validation revealing the limits of detection (LOD) and quantification (LOQ) for quercetin. Additionally, agro-industrial waste onion peel, enriched with phenolic compounds such as quercetin, was subjected to solid-phase extraction using MMIP for the purification of quercetin., 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.)

Introduction: The quality of Chinese medicine preparations can be greatly influenced by the quality of the intermediates such as extracts or concentrates. However, it is highly challenging to evaluate the quality in a rapid and non-contact manner during manufacturing. Here, we introduce an intelligent hyperspectral analysis method integrating a self-built abnormal region removal algorithm with machine learning and demonstrate its utility using the concentrate of Weifuchun (WFC), a traditional Chinese medicine preparation made from Ginseng Radix et Rhizoma Rubra, Rabdosia Amethystoides, and Aurantii Fructus., Objective: To rapidly and non-destructively detect quality attributes of the intermediates in the manufacturing processes of Chinese medicine, an intelligent hyperspectral analysis method was developed for simultaneously quantifying the contents of naringin, neohesperidin, rosmarinic acid, and relative density of WFC concentrates., Methodology: Samples were evenly spread on solid white flat bottom containers, which were batch placed on a horizontal sample stage. Subsequent to the acquisition of near-infrared (NIR) hyperspectral images, abnormal pixels such as large/small bubbles and fine solids were first removed according to the differential pixel values in the binary grayscale map and the Mahalanobis distance metric. Then, partial least squares (PLS) and support vector machine (SVM) algorithms were used to construct hyperspectral quantitative calibration models for quality attributes. The hyperspectral images were reconstructed based on these models to visually evaluate the quality of the concentrates during manufacturing., Results: As a case study, quality attributes of the WFC concentrates including contents of naringin, neohesperidin, rosmarinic acid, and relative density were determined simultaneously, and coefficients of determination of these quantitative correction models were 0.900, 0.891, 0.851, and 0.920, respectively., Conclusion: The method proposed in this study favors real-time determination of multiple attributes in viscous samples with industrial application prospects., (© 2024 John Wiley & Sons Ltd.)

Introduction: Quality evaluation of Huang-qin is significant to ensure its clinical efficacy., Objective: This study aims to establish an accurate, rapid and comprehensive Huang-qin quality evaluation method to overcome the time-consuming and laborious shortcomings of traditional herbal medicine quality assessment methods., Methods: The contents of baicalin, baicalein and scutellarin in Huang-qin from five different origins were analyzed by FT-IR and NIR spectra combined with multivariate data technology. The quality of Huang-qin from different origins was evaluated by TOPSIS and consistency analysis based on the content of three active ingredients. The correlation between ecological factors and the accumulation of active ingredients was explored., Results: Satisfactory prediction results of PLS models were obtained. Relatively, the model based on FT-IR combined with the PLS regression method has higher R 2 and smaller RMSE than the NIR combined with the PLS method. TOPSIS and consistency analysis results showed that the quality of Huang-qin from different geographical origins was significantly different. The results showed that the quality of Huang-qin produced in Shanxi Province was the best among the five origins studied. The results also found that the quality of Huang-qin in different growing areas of the same origin was not completely consistent. The correlation study showed that altitude, sunshine duration and rainfall were the main factors that caused the quality difference of medicinal materials in different geographical origins., Conclusion: This study provides a reference for the rapid quantitative analysis of the active components of herbal medicine and the quality evaluation of them., (© 2024 John Wiley & Sons Ltd.)

This study established an ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method to determine the content of five index components in rat tissues and organs after administration of Shuganning Injection or Scutellariae Radix extract. The dynamic changes and differences of the distribution of the five index components over time between the two groups were studied, and the effects of Scutellariae Radix alone or in combination with other medicines on the tissue distribution of the five components were explored. After Shuganning Injection or Scutellariae Radix extract was injected into the tail vein of rats, the heart, liver, spleen, lung, kidney, stomach, intestine, and brain tissue samples were collected at four time points of 0.17, 0.5, 1, and 2 h, respectively. UPLC-MS/MS was employed to measure the concentrations of the five index components(baicalin, baicalein, oroxylin A, oroxylin A-7-O-β-D-glucuronide, and scutellarin) in the samples of the two groups. The results showed that the established method was simple, fast, and exclusively stable. After the administration of Shuganning Injection and Scutellariae Radix extract, the five index components presented wide distribution and had differences in vivo. The two groups showcased abundant distribution of baicalin, baicalein, and oroxylin A in the kidney and liver, oroxylin A-7-O-β-D-glucuronide in the kidney and brain, and scutellarin in the kidney and heart. The content of baicalin in the heart, liver, kidney, and intestine, baicalein in the liver and kidney, and oroxylin A in the lung after administration of Shuganning Injection(Scutellariae Radix in combination with other medicines) was significantly higher than that after administration of Scutellariae Radix extract. The results of this study suggested that the five components of Shuganning Injection and Scutellariae Radix extract demonstrated wide distribution without accumulation in rats. The combination of Scutellariae Radix with other medicines can increase the distribution of active components in rats, which provided a basis for explaining the rationality of the compatibility of Shuganning Injection from in vivo processes.

Ethanolic extracts of Baikal skullcap ( Scutellaria baicalensis ) root were obtained using various techniques, such as maceration, maceration with shaking, ultrasound-assisted extraction, reflux extraction, and Soxhlet extraction. The influence of the type and time of isolation technique on the extraction process was studied, and the quality of the obtained extracts was determined by spectrophotometric and chromatographic methods to find the optimal extraction conditions. Radical scavenging activity of the extracts was analyzed using DPPH assay, while total phenolic content (TPC) was analyzed by the method with the Folin-Ciocalteu reagent. Application of gas chromatography with mass selective detector (GC-MS) enabled the identification of some bioactive substances and a comparison of the composition of the particular extracts. The Baikal skullcap root extracts characterized by both the highest antioxidant activity and content of phenolic compounds were obtained in 2 h of reflux and Soxhlet extraction. The main biologically active compounds identified in extracts by the GC-MS method were wogonin and oroxylin A, known for their broad spectrum of biological effects, including antioxidant, anti-inflammatory, antiviral, anticancer, and others.

Danggui-Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this study, high-performance liquid chromatography was used to determine four components of Shaoyao Gancao Decoction (SGD), and the effect of purification was evaluated using fingerprints, similarity analysis and cell experiments. An effective method for isolation and purification of SGD was established. The adsorption/desorption properties of SGD were evaluated using resin screening, isothermal analysis, adsorption kinetics, and dynamic adsorption-desorption experiments. It was shown that the Langmuir equation fitted the isotherm data well and that a pseudo-second-order model accurately described kinetic adsorption on AB-8 resin. Analysis of thermodynamic parameters showed that the adsorption process was exothermic. Under the optimal process conditions, the concentrations of albiflorin, paeoniflorin, liquiritin and ammonium glycyrrhizinate in the product were 73.05, 134.04, 45.04 and 75.00 mg/g, respectively. The yields of the four components were 71.89 %-86.19 %. Cell experiments showed that the purified SGD retained anti-inflammatory activity. This research lays the foundation for the separation and purification of SGD and subsequent preparation research., 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.)

Knowing the true levels of nutrients and dietary bioactives in fruit juices at the point of consumption is key to properly understand their potential health benefits. The objective was to characterise the vitamin C and flavanone content in commercial orange juices consumed in Europe, compared with fresh-squeezed juices. Commercial juices were a rich source of vitamin C (>30% of the Nutrient Reference Value). Vitamin C in fresh-squeezed juices, at the end of their shelf-life, remained 33% higher than the levels found in the commercial juices. Flavanones had similar values from both commercial and fresh juices, except for fresh samples stored for 48 h, where fresh juices had higher values (22.36 mg/100 mL). Thus, orange juices preserve their bioactive compounds during storage, with very little influence of the brand, country, industrial process or storage conditions. Main bioactive compounds in commercial juices are present at nutritionally significant levels to the freshly-squeezed ones.

Naringin is a flavonoid found primarily in citrus species with especially high concentrations being present in grapefruit ( Citrus paradisi ), bitter orange ( Citrus aurantium ), and pomelo ( Citrus grandis ). Because of its many positive effects on human health, naringin has been the focus of increasing attention in recent years. Recently, conventional extraction methods have been commonly replaced with unconventional methods, such as ultrasound-assisted extraction (UAE) and other, more eco-friendly extraction methods requiring little-to-no environmentally harmful solvents or significantly less energy. Naringin analysis is most commonly done via high-performance liquid chromatography (HPLC), and ultrahigh-performance liquid chromatography (UHPLC) coupled with a mass spectrometer (MS) or a photodiode array (DAD) detector. The aim of this review is to provide an overview of recent trends developments in the extraction, sample preparation, and liquid chromatographic analysis of the compound originating from citrus fruits or their products.

Butin and butein are significant bioactive flavanones derived from plants, existing as tautomers of each other. However, their physicochemical attributes, such as their spectral profiles under varying experimental conditions in aqueous solutions and established chromatographic methods for distinguishing between them, remain undetermined. In this study, we determined the basic properties of butin and butein using conventional spectroscopic, reversed-phase, and chiral HPLC analyses. The spectra of the synthesized butin and butein were analyzed using a UV-Vis spectrophotometer in several solvents with different polarities as well as in aqueous solutions at various pH values. Furthermore, the behavior of the measured spectra was reproduced by calculations to reveal the effects of the solvent and pH on the spectra of butin and butein in organic and aqueous solutions. Subsequently, we assessed the structural stability of butin and butein using reversed-phase HPLC, which revealed that butein is unstable compared with butin in a general culture medium. The synthesized butin was effectively separated into R- and S-isomers with positive and negative Cotton effects, respectively, via HPLC using a chiral column. These findings will aid in uncovering the individual properties of both butin and butein that may have been concealed by their tautomerism and enable the synthesis of S-butin, which is typically challenging and time-consuming to isolate.

Two previously undescribed compounds, namely dalpulapans F and G ( 1 and 2 ), along with 11 known compounds were isolated from the MeOH crude extract of the roots of Dalbergia stipulacea . Dalpulapan F was found as a rare isoflavone-quinone derivative. Their structures and absolute configurations were supported by extensive spectroscopic data analysis, including 1 D and 2 D NMR, HRESIMS data, specific rotation data, and comparison of the experimental and calculated ECD data. Cytotoxicity evaluation of the isolated compounds against HepG2 and KKU-M156 cell lines revealed that isoflavonoid 9 and rotenoid 13 exhibited the most activity against the two cell lines.

Dracocephalum jacutense Peschkova is a rare and endangered species of the genus Dracocephalum of the Lamiaceae family. The species was first described in 1997 and listed in the Red Data Book of Yakutia. Significant differences in the multicomponent composition of extracts from D. jacutense collected in the natural environment and successfully introduced in the Botanical Garden of Yakutsk were identified by a team of authors earlier in a large study. In this work, we studied the chemical composition of the leaves, stem, and inflorescences of D. jacutense using the tandem mass spectrometry method. Only three cenopopulations of D. jacutense were found by us in the territory of the early habitat-in the vicinity of the village of Sangar, Kobyaysky district of Yakutia. The aboveground phytomass of the plant was collected, processed and dried as separate parts of the plant: inflorescences, stem and leaves. Firstly, a total of 128 compounds, 70% of which are polyphenols, were tentatively identified in extracts of D. jacutense . These polyphenol compounds were classified as 32 flavones, 12 flavonols, 6 flavan-3-ols, 7 flavanones, 17 phenolic acids, 2 lignans, 1 dihydrochalcone, 4 coumarins, and 8 anthocyanidins. Other chemical groups were presented as carotenoids, omega-3-fatty acids, omega-5-fatty acids, amino acids, purines, alkaloids, and sterols. The inflorescences are the richest in polyphenols (73 polyphenolic compounds were identified), while 33 and 22 polyphenols were found in the leaves and stems, respectively. A high level of identity for polyphenolic compounds in different parts of the plant is noted for flavanones (80%), followed by flavonols (25%), phenolic acids (15%), and flavones (13%). Furthermore, 78 compounds were identified for the first time in representatives of the genus Dracocephalum , including 50 polyphenolic compounds and 28 compounds of other chemical groups. The obtained results testify to the unique composition of polyphenolic compounds in different parts of D . jacutense .

Citrus fruits have been the subject of extensive research over the years due to their impressive antioxidant properties, the health benefits of flavanones, and their potential use in the prevention and treatment of chronic diseases. Grapefruit have been shown in studies to improve overall health, with numerous potential benefits, including improved heart health, reduced risk of certain cancers, improved digestive health, and improved immune system function. The development of cyclodextrin complexes is an exciting approach to increasing the content of flavanones such as naringin and naringenin in the extraction medium while improving the profile of beneficial phenolic compounds and the antioxidant profile. This research aims to optimize the extraction conditions of the flavanones naringin and naringenin with additional compounds to increase their yield from different parts of grapefruit ( Citrus × paradisi L.) fruits, such as albedo and segmental membranes. In addition, the total content of phenolic compounds, flavonoids, and the antioxidant activity of ethanolic extracts produced conventionally and with -cyclodextrin was examined and compared. In addition, antioxidant activity was measured using the radical scavenging activity assay (ABTS), radical scavenging activity assay (DPPH), and ferric reducing antioxidant power (FRAP) methods. The yield of naringin increased from 10.53 ± 0.52 mg/g to 45.56 ± 5.06 mg/g to 51.11 ± 7.63 mg/g of the segmental membrane when cyclodextrins (α, β-CD) were used; naringenin increased from 65.85 ± 10.96 μg/g to 91.19 ± 15.19 μg/g of the segmental membrane when cyclodextrins (α, β-CD) were used. Furthermore, the results showed that cyclodextrin-assisted extraction had a significant impact in significantly increasing the yield of flavanones from grapefruit. In addition, the process was more efficient and less expensive, resulting in higher yields of flavanones with a lower concentration of ethanol and effort. This shows that cyclodextrin-assisted extraction is an excellent method for extracting valuable compounds from grapefruit.

Background: Scutellaria baicalensis, a medicinal herb belonging to the Lamiaceae family, has been recorded in the Chinese, European, and British Pharmacopoeias. The medicinal properties of this plant are attributed to the total flavonoids of Scutellaria baicalensis (TFSB), particularly the main component, baicalin. This study provides a systematic and comprehensive list of the identified TFSB components and their chemical structures. The quality control process, pharmacokinetics, clinical application, and safety of Scutellaria baicalensis are discussed, and its pharmacological effect on cardiovascular diseases (CVDs) is detailed. Finally, the future research trends and prospects of this medicinal plant are provided., Methods: The Chinese and English papers related to TFSB were collected from the PubMed and CNKI databases using the relevant keywords. To highlight the pharmacological mechanism, clinical application, and safety of TFSB, the collected articles were screened and classified based on their research content., Results: TFSB contains at least 100 different kinds of flavonoids, of which baicalin, baicalein, wogonin, wogonoside, scutellarin, and scutellarein are the main active ingredients. The preparation process of TFSB is relatively well established, and the extraction rate can be significantly increased by enzymatic pretreatment and ultrasonication. The low oral availability of TFSB may be effectively enhanced using nanoformulations. The available pharmacokinetic data show that flavonoid glycosides and aglycones with the same parent nucleus may be converted to structures that are conducive to absorption in vivo. Moreover, TFSB can protect against CVDs by inhibiting apoptosis, regulating oxidative stress response, participating in inflammatory response, protecting against myocardial fibrosis, inhibiting myocardial hypertrophy, and regulating blood vessels. In terms of clinical application and animal safety, the available studies show that TFSB can be applied in a wide range of clinical treatments and is safe to use is animals., Conclusion: This article systematically reviews the therapeutic effect and underlying pharmacological mechanism of TFSB against CVDs. The available studies clearly suggest that TFSB has great potential for the treatment of CVDs and is worthy of in-depth research and development., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest in publishing this work in whole or in part., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Forty-one flavones, each one of flavonol, chalcone and dihydroflavonol, two flavanones, and four phenylethanoids were isolated from corollas, calyces and leaves of two Aeschynanthus species, A. fulgens and A. pulcher, and six cultivars, 'Mahligai', 'Mona Lisa', SoeKa', 'Redona', 'Freshya' and 'Bravera'. Flavonoids were mainly the glucuronides and/or methylglucuronides based on hispidulin, nepetin, pectolinarigenin, 6-hydroxyluteolin, scutellarein, apigenin and luteolin, and identified by UV spectra, HR-MS, LC-MS, acid hydrolysis, NMR, and/or HPLC and TLC comparisons with authentic samples. Of these flavonoids, twelve, i.e. hispidulin 7,4'-di-O-glucuronide, 7,4'-di-O-methylglucuronide, 7-O-methylglucuronide-4'-O-glucuronide, 7-O-glucuronide-4'-O-methylglucuronide, 7-O-glucosyl-(1 → 2)-glucuronide and 8-C-glucoside, nepetin 7,4'-di-O-glucuronide, 7-O-glucuronide-4'-O-methylglucuronide and 7-O-methylglucuronide-4'-O-glucuronide, pectolinarigenin 7-O-glucosyl-(1 → 2)-glucuronide and 7-O-xylosyl-(1 → 2)-(6″-malonylglucoside), and 6-hydroxyluteolin 7,4'-di-O-glucuronide, were previously undescribed., Competing Interests: Declaration of competing interest The authors declare that they no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, full scan (FS)-parent ions list (PIL)-higher energy collision induced dissociation (HCD)-MS/MS (FS-PIL-HCD-MS/MS) was used to acquire the chemical profile of flavonoids in Scutellaria barbata. Mass defect filtering (MDF) induced subtype classification and diagnostic product ions (DPIs) dominated structural confirmation were integrated into an effective strategy for the systematic screening and identification of the flavonoids. An in-house flavonoid MS database based on molecular design was established to construct a modified triangle MDF algorithm for progressive screening and subtype classification. The obtained results demonstrated that the modified MDF was capable of simplifying the workload in formula editing and subsequent screening process, and distinguishing different subtypes. The fragmentation behaviors of eleven reference standards were evaluated to obtain the MS 2 fragmentation pathway and DPIs which can provide a criterion to eliminate false-positive results and judge the target flavonoids with the exact number and position of substituents for the first time. Structure confirmation was characterized by comparing with the reference substance, searching the database, and analyzing DPIs. To distinguish some isomers, ClogP (the calculated lipophilicity parameter) was adopted. As a result, 127 target flavonoids, including 30 flavone/flavonol aglycones, 10 flavanone/flavanonol aglycones, 49 flavone/flavonol monoglycosides, 16 flavanone/flavanonol monoglycosides, 21 flavone/flavonol diglycosides and 1 flavanone/flavanonol diglycoside, were ultimately identified or tentatively characterized based on the MS fragmentation pathway and DPIs analysis. This study provides a novel MDF method with improved subtype classification and develops a novel strategy for the progressive screening, subtype classification and systematic characterization of complex components in herbal medicines., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

The impact of β-glucan on the bioavailability of orange juice (OJ) flavanones was investigated in a randomised controlled trial. Volunteers consumed 500 mL of OJ without or with either 3 g (OB-3) or 6 g (OB-6) of β-glucan. Urine samples, collected 12 h before and over a 0-24 h period post-supplementation, were analysed by high-performance liquid chromatography-high resolution mass spectrometry. The overall 0-24 h urinary excretion of the 17 flavanone metabolites identified and quantified in urine after OJ ingestion corresponded to 29.7 µmol, and 25.0 and 9.3 µmol, respectively, after OB-3 and OB-6 intake. This corresponds to 9.3, 7.9, and 2.9% recoveries of the 318 µmol of the ingested flavanones. The acute ingestion of OJ with 6 g, but not 3 g of β-glucan led to a significant reduction ( p  < 0.05) in the excretion of flavanone metabolites compared with consumption of OJ alone.

From the methanolic extract of the rhizomes of Boesenbergia pandurata , a new flavanone derivative named (2 R ,7″ S )-8-(1-phenyl-2-carboxyethyl)pinocembrin ( 1 ) and four known flavonoids ( 2 - 5 ) were isolated. Its absolute configuration was concluded by NMR and MS spectroscopic analysis, together with comparison between experimental and calculated ECD data. In turn, compound 1 exhibited strong cytotoxicity against the PANC-1 human pancreatic cancer cell line with a PC 50 value of 6.4 µM under nutrient-deprived conditions, comparable with that of arctigenin (PC 50 , 0.83 µM).

It is of great theoretical interest and industrial significance to improve the extraction efficiency of baicalein and wogonin from Scutellaria baicalensis roots because of their high pharmacological activities. The present study was aimed to establish the optimized ultrasound-assisted enzymatic pretreatment (UAEP) process by which ultrasound irradiation and the exogenous enzyme were simultaneously applied to efficiently transform baicalin and wogonoside into baicalein and wogonin, enhancing their extraction efficiency. Single-factor experiment and Box-Behnken design were used to optimize the main UAEP conditions to maximize the total extraction yield of baicalein and wogonin. The optimized UAEP conditions were cellulase concentration of 1.1%, pH of 5.5, UAEP temperature of 56.5 °C, UAEP time of 39.4 min, and ultrasonic power of 200 W with the total extraction yield of 82.51 ± 0.85 mg/g DW. The comparison of the established technique with the reference method based on the enzymatic pretreatment revealed that the productive efficiency was significantly improved with the transformation rates nearly doubled. These results suggest that the optimized UAEP process has the potential to be applied for the green, simple, and efficient extraction of baicalein and wogonin in the pharmaceutical and food industry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Naringenin, a flavonoid compound found in pummelo, is a key biological active compound in some traditional Chinese medicines, including Citri reticulatae pericarpium, Citri reticulatae pericarpium viride, Aurantii fructus immaturus, and Aurantii fructus. These Chinese medicinal preparations are the peels or immature fruits of certain citrus species. Aiming at detecting naringenin in complex matrices such as pummelo and traditional Chinese medicines, we put forward a sensitive and practical indirect competitive enzyme-linked immunosorbent assay (icELISA) based on anti-naringenin monoclonal antibodies (anti-Nar-mAbs). The median inhibitory concentration (IC 50 ) was 4.43 ng/mL, and the working range was 1.15-15.81 ng/mL. The findings of the icELISA for the analysis of naringenin in pummelo and herb samples had a good correlation with the ultra performance liquid chromatography (UPLC) methodology and showed good accuracy and reproducibility. These data demonstrated that the developed icELISA is reliable, accurate, and suitable for detecting naringenin in pummelo and traditional Chinese medicines., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: The structural annotation of target relies on high-resolution mass spectrometry (HRMS) information resulting in dubious identities in most cases. The accurate annotation of isomeric structures is still challenging to be confirmed with significant bottleneck., Objective: This study focused on the improvement of structural annotation of candidate structures via four pairs of isomeric flavanone-7-O-diglucosides and their basic flavanone aglycones commonly detected in citrus products., Method: An integrated liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) approach merging retention time, accurate mass, tandem mass spectrometry (MS/MS) information (diagnostic ions), ion ratio at selected collision energy was established successfully., Results: Feasibility of this approach was validated confidently in biological samples with relative standard deviation (RSD) of ion ratio range from 3.91 to 12.28%. Differences of fragmentation patterns of citrus flavanones were illustrated reasonably. MS/MS fragments of (S)-hesperetin and (S)-isosakuranetin were complicated and showed typical radical ion [ 1,2 A - H] •- (m/z 164) in negative ESI mode due to the methoxyl group on B-ring, which showed huge difference with (R)-hesperetin and (R)-isosakuranetin., Conclusion: This study integrated multiple levels to boost the confidence of structural annotation relied on LC-HRMS, and provided important values in practice for precise identification of citrus flavanones in biological matrices., (© 2020 John Wiley & Sons, Ltd.)

In this study, an electrochemical sensor was designed for the detection of narirutin using three-dimensional nanostructured porous nickel on screen-printed electrode (3DnpNi/SPE). The modified electrode was successfully synthesized by the dynamic hydrogen bubble template method. The 3DnpNi/SPE was characterized by spectroscopic, microscopic, and electrochemical methods. The results showed that the 3DnpNi/SPE presents good electrocatalytic activity for the oxidation of narirutin. The quantification of narirutin was conducted by differential pulse voltammetry, which showed a wide concentration range (1.0 × 10 -7 - 1.0 × 10 -5 mol L -1 ), with low detection limit (3.9 × 10 -8 mol L -1 ), and excellent sensitivity (0.31 A L mol -1 ). The proposed electrode was applied toward the determination of narirutin in yellow water sample from the citrus industry, where it presented a good degree of accuracy. The 3DnpNi/SPE showed repeatability, long-term stability, and selectivity. The results obtained showed agreement with those obtained by HPLC/DAD method. Chemical compounds studied in this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although physiologically pain has a protective function, in many diseases, it is one of the most prominent symptoms. Today, new trends are focused on finding more natural alternatives to conventional treatments to alleviate it. Thereby, the purpose of this investigation was to obtain preclinical data of the antinociceptive properties of a lyophilized obtained from a newly designed maqui-citrus beverage alone and added with different sweeteners. To achieve this objective, maqui berry and citrus pharmacological activity were studied separately, as well as the interaction of both ingredients. In addition, due to the controversy generated regarding the intake of sugars, related to different metabolic diseases, the influence of different sweeteners (stevia, sucralose, or sucrose) was studied to determine their possible influence on the bioactive compounds of this product. For the attainment of our goals, a pharmacological evaluation, using the 1% formalin test, a nociceptive pain model in mice, was performed by using a sub-efficacious dosage of Maqui (25 mg/kg, i.p.) alone and combined with citrus, and then compared with the effects obtained in the presence of the different sweeteners. As a result, the antinociceptive response of the maqui was synergized in the presence of citrus in the neurogenic and inflammatory phases of the formalin test. However, this response was partially or totally reduced in the presence of the sweeteners. Our study gives preclinical evidence that a combination of maqui and citrus might exert beneficial actions to relieve pain, whereas the presence of sweeteners could reduce or avoid it.

Comprehensive characterization of traditional Chinese medicine prescriptions has long been a hurdle due to the chemical complexity and the lack of analytical tools. Mahuang decoction is a well-known traditional Chinese medicine prescription widely used for sweating and relieving the exterior, relieving cough and asthma, but it was insufficiently chemically scrutinized. In this study, the chemical component information of Mahuang decoction was investigated by ultrahigh-performance liquid chromatography tandem linear ion trap-Orbitrap mass spectrometry. A new data processing tool, feature-based molecular networking, was introduced for grouping and elucidating the compounds. In this way, 156 chemical components were identified or tentatively characterized, including alkaloids, triterpenoid saponins, flavanone-O-glycosides, flavone-C-glycosides, and procyanidins. Thus, this research provides a solid foundation for further development of Mahuang decoction, and the adopted method is expected to be applied to other traditional Chinese medicine prescriptions., (© 2021 Wiley-VCH GmbH.)

The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms ( p -value AB vs. Control: 0.009; p -value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.

To study the simultaneous effect of the molecular gradient of polyphenols (curcumin, trans -resveratrol, and wogonin) and biological factors released from tumor cells on apoptosis of adjacent cells, a novel microfluidic system was designed and manufactured. The small height/volume of microfluidic culture chambers and static conditions allowed for establishing the local microenvironment and maintaining undisturbed concentration profiles of naturally secreted from cells biochemical factors. In all trials, we observe that these conditions significantly affect cell viability by stimulating cell apoptosis at lower concentrations of polyphenols than in traditional multiwell cultures. The observed difference varied between 20.4-87.8% for curcumin, 11.0-37.5% for resveratrol, and 21.7-62.2% for wogonin. At low concentrations of polyphenols, the proapoptotic substances released from adjacent cells, like protein degradation products, significantly influence cell viability. The mean increase in cell mortality was 38.3% for microfluidic cultures. Our research has also confirmed that the gradient microsystem is useful in routine laboratory tests in the same way as a multiwell plate and may be treated as its replacement in the future. We elaborated the new repetitive procedures for cell culture and tests in static gradient conditions, which may become a gold standard of new drug investigations in the future.

The present study describes the peculiar phytochemical characteristics of bergamots cultivated in distinct islands of the Ionian Sea. Ultrahigh-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS) supported by 1 and 2D NMR spectroscopy was used for unambiguous metabolic profiling of albedo, flavedo and juice samples. Profile differences were determined using a multi-analytical clustering approach based on high-performance thin-layer chromatography fingerprints and UHPLC-HRMS data. Finally, a validated HPLC method offering good precision (0.12-0.94%) and accuracy (95.25-103.93%) was proposed for the quantification of the major flavanones. A total of 37 secondary metabolites were characterized belonging to flavonoids, limonoids and coumarins. Their distribution was tissue-dependent and varied significantly from bergamots of other geographical locations. Surprisingly, neoeriocitrin was the major flavanone, reaching 1.69 ± 0.05 g/L in the juice and 5.24 ± 0.12 mg/g in albedo. This is the highest reported amount among Citrus species, rendering Ionian bergamots a promising candidate for novel functional products., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A simple and sensitive in situ antioxidation process assisted with a matrix solid-phase dispersion method for extracting chiral flavonoids in citrus fruit was established, and samples were further analyzed using ion mobility quadrupole time-of-flight high-resolution mass spectrometry. The collision cross-sections of the target compounds were studied using single-field and stepped-field methods. The optimal conditions were obtained using 30 mg of C 18 as a dispersant, methanol as an elution solvent and 0.6 mM 1,1-diphenyl-2-picrylhydrazyl (DPPH) as a radical solution. Additionally, the method showed satisfactory limits of detection (3.70-6.52 ng/mL) and good recoveries (96.78-104.67%) for four flavonoids in citrus fruit. The IC 50 values of DPPH radical-scavenging activities ranged from 817.8 to 981.55 μg/mL for tested samples. The method was a good alternative for the microextraction and determination of antioxidant capacity and chiral differentiation of narirutin, naringin, hesperidin and neohesperidin in citrus fruit., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The physico-chemical quality parameters (external and internal color, firmness, acidity, total soluble solids, anthocyanins, sugars, hydroxycinnamic acids and flavanones) of 'Moro' and 'Tarocco Rosso' blood oranges grafted onto eight different rootstocks at three harvest time were studied. The rootstocks were 'Carrizo', 'C-35', 'Cleopatra' mandarin, 'Citrus volkameriana', 'Citrus macrophylla', 'Swingle' citrumelo, 'Forner-Alcaide 5' and 'Forner-Alcaide 13'. All studied parameters were highly rootstock/scion-dependent and showed changes throughout harvest. The content of the main anthocyanins revealed their relation with internal fruit color in both cultivars. The rootstocks that led to fruit with the lowest anthocyanins displayed the least sucrose content. The differences detected in the amount of hydroxycinnamic acids (chlorogenic, ferulic and sinapic) and flavanones (hesperidin, narirutin and didymin) related to anthocyanins content, explained phenylpropanoid pathway., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Xiaoyaosan is one of the famous formulas treating for liver, spleen and blood deficiency syndrome along Chinese history. Their five main components, paeoniflorin, ferulic acid, glycyrrhizic acid, liquiritin, and atractylenolide I are believed to partly representative of this formula. Ultra performance liquid chromatography method was newly established, UPLC BEH-C18 column (2.1 × 100 mm, 1.7 μm) with acetonitrile - 0.1% phosphate acid gradient elution system, in 0.4 mL/min and the temperature was 30 °C; Detection wavelengths were optimized separately. The five components were linear within their linear range ( r  ≥ 0.9991), average recovery 97.63%∼102.83%, RSD 1.88%∼4.38%. The newly established method is accurate, rapid, and convenient, with satisfied separation performance to quantify multi-components in formula and preparations of Xiaoyaosan. It will provide a reliable reference for the quality evaluation of both Xiaoyaosan formula and preparations during the process of manufacture, administration and clinical application in the future.

Asarinin, β-eudesmol, and wogonin have common antiangiogenic activities and have the potential for use in chemotherapy. Besides, they are multivalent substances that are combined in various herbal medicines. The purpose of this study was to develop a method for simultaneous analysis of asarinin, β-eudesmol, and wogonin, which are representative pharmacological components of Asarum heterotropoides, Atractylodes lancea, and Scutellaria baicalensis, respectively, in rat biosamples using ultraperformance liquid chromatography-tandem mass spectrometry. The three components were separated using 5 mm aqueous ammonium acetate containing 0.1% formic acid and acetonitrile as a mobile phase, equipped with a KINETEX core-shell C 18 column. The analysis was quantitated on a triple-quadrupole mass-spectrometer employing electrospray ionization, and operated in the multiple reaction monitoring mode. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma, urine, and feces constituents. The developed analytical method satisfied international guidance criteria and could be successfully applied to the pharmacokinetic (PK) studies evaluating oral bioavailability of asarinin, β-eudesmol, and wogonin after oral and intravenous administration and their urinary and fecal excretion ratios after oral administration to rats. Furthermore, the analysis was extended to PK studies following oral administration of Gumiganghwal-tang. This study was the first simultaneous analysis of the aforesaid three constituents in rat plasma, urine, and feces that also determined their PK parameters., (© 2020 John Wiley & Sons, Ltd.)

The metabolic profile of Lavado cocoa was characterized for the first time by NMR spectroscopy, then compared with the profiles of fermented and processed varieties, Natural and commercial cocoa. The significant difference in the contents of theobromine and flavanols prompted us to examine the cocoa varieties to seek correlations between these metabolite concentrations and the anti-amyloidogenic activity reported for cocoa in the literature. We combined NMR spectroscopy, preparative reversed-phase (RP) chromatography, atomic force microscopy, in vitro biochemical and cell assays, to investigate and compare the anti-amyloidogenic properties of extracts and fractions enriched in different metabolite classes. Lavado variety was the most active and the catechins and theobromine were the chemical components of cocoa hindering Aβ peptide on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Yanghe decoction is a traditional Chinese medicine prescription and has been used for breast cancer treatment for many years. However, the effective ingredients in the decoction have not been identified. The expression of poly(ADP-ribose) polymerase-1 is highly related to breast cancer. Using poly(ADP-ribose) polymerase-1 as a probe, we expressed the haloalkane dehalogenase-tagged protein in BL21(DE3) E. coli, immobilized it on hexachlorocaproic acid-modified macroporous silica gel, and established a poly(ADP-ribose) polymerase-1 chromatographic model. The feasibility of the model was verified by testing the retention behaviors of five drugs on the protein column. We applied the model in screening the bioactive components in yanghe decoction. Rutin, liquiritin, and a compound ([M-H] - 681.7) were identified to be the potential bioactive ingredients. We studied the binding property between rutin and poly(ADP-ribose) polymerase-1 by injection amount dependent method, competitive studies, and molecular docking. We found that rutin can bind to the protein through the typical inhibitor binding site of the protein. Therefore, the chromatographic model is a useful tool to screen bioactive compounds from traditional Chinese medicine. The method is fast, reliable, and applicable to other functional proteins that can screen the potential lead compounds for the treatment of the related diseases., (© 2020 Wiley-VCH GmbH.)

Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19-40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo- O -glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo- O -glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.

The current study was focused on new approaches for debittering of by-products like kinnow pomace and kinnow pulp residue by using various food grade mild chemical methods, such as alkali treatment, acid treatment, and solventogenesis. Whereas in the studied various chemical treatments, the solventogenesis method with acetone resulted in maximum extraction of naringin and limonene from kinnow pomace and pulp residue and showed high acceptability for food product development. The acetone treatment was further optimized by RSM for the maximum extraction of naringin and limonene. Under optimized conditions, the maximum amount of naringin and limonene extracted were found to be 8.955, 2.122 mg/g from kinnow pomace and 9.971, 3.838 mg/g from pulp residue, respectively. This process can not only result in the effective utilization of agro-industrial by-product but also provide a sustainable solution to the environmental pollution caused by kinnow juice industry., 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 © 2020 Elsevier Ltd. All rights reserved.)

The compound (2 S )-eriodictyol is an important flavonoid that can be derived from (2 S )-naringenin through flavonoid 3'-hydroxylase (F3'H) catalyzation. F3'H is a cytochrome P450 enzyme that requires a cytochrome P450 reductase (CPR) to function. However, P450s have limited applications in industrial scale biosynthesis, owing to their low activity. Here, an efficient Sm F3'H and a matched Sm CPR were identified from Silybum marianum . To improve the efficiency of Sm F3'H, we established a high-throughput detection method for (2 S )-eriodictyol, in which the promoter combination of Sm F3'H and Sm CPR were optimized in Saccharomyces cerevisiae . The results revealed that Sm F3'H/ Sm CPR should be expressed by using promoters with similar and strong expression levels. Furthermore, directed evolution was applied to further improve the efficiency of Sm F3'H/ Sm CPR. With the optimized promoter and mutated combinations Sm F3'H D285N / Sm CPR I453V , the (2 S )-eriodictyol titer was improved to 3.3 g/L, the highest titer in currently available reports. These results indicated that S. cerevisiae is an ideal platform for functional expression of flavonoid related P450 enzymes.

Objective: To explore the molecular mechanism of Simiao powder in the treatment of knee osteoarthritis., Methods: Based on oral bioavailability and drug-likeness, the main active components of Simiao powder were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). GeneCard, OMIM, DisGeNET, DrugBank, PharmGkb, and the Therapeutic Target Database were used to establish target databases for knee osteoarthritis. Cytoscape software was used to construct a visual interactive network diagram of "active ingredient - action target - disease." The STRING database was used to construct a protein interaction network and analyze related protein interaction relationships. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis were performed on the core targets. Additionally, Discovery Studio software was used for molecular docking verification of active pharmaceutical ingredients and disease targets., Results: Thirty-seven active components of Simiao powder were screened, including 106 common targets. The results of network analysis showed that the targets were mainly involved in regulating biological processes such as cell metabolism and apoptosis. Simiao powder components were predicted to exert their therapeutic effect on the AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. The molecular docking results showed that the active components of Simiao powder had a good match with the targets of IL1B, MMP9, CXCL8, MAPK8, JUN, IL6, MAPK1, EGF, VEGFA, AKT1, and PTGS2., Conclusion: Simiao powder has multisystem, multicomponent, and multitarget characteristics in treating knee osteoarthritis. Its possible mechanism of action includes inhibiting the inflammatory response, regulating immune function, and resisting oxidative stress to control the occurrence and development of the disease. Quercetin, wogonin, kaempferol, beta-sitosterol, and other active ingredients may be the material basis for the treatment of knee osteoarthritis., Competing Interests: All authors declare there are no competing interests., (Copyright © 2020 Zhengquan Huang et al.)

Dietary guidelines recommend the consumption of flavonoid-rich extracts for several health benefits. Although immature Citrus unshiu pomace (ICUP) contains high levels of flavanone glycosides, many studies have concentrated on the optimization of flavonoid extraction from mature citrus peels. Therefore, we developed an optimized extraction method for hesperidin and narirutin from ICUP, and evaluated their antioxidant activities using ten different assay methods. The extraction conditions for the highest flavonoid yields based on a response surface methodology were 80.3 °C, 58.4% (ethanol concentration), 40 mL/g (solvent/feed), and 30 min, where the hesperidin and narirutin yields were 66.6% and 82.3%, respectively. The number of extractions was also optimized as two extraction steps, where the hesperidin and narirutin yields were 92.1% and 97.2%, respectively. Ethanol was more effective than methanol and acetone. The ethanol extract showed high scavenging activities against reactive oxygen species but relatively low scavenging activities for nitrogen radicals and reactive nitrogen species. The antioxidant activities showed a higher correlation with hesperidin content than narirutin content in the extracts. This study confirms the potential of an optimized method for producing antioxidant-rich extracts for the functional food and nutraceutical industries.

Citrus by-products are inexpensive sources of polyphenols, important bioactive compounds with wide pharmaceutical and food applications. This study aimed to investigate the effect of enzymatic treatment of citrus by-products on the polyphenolic profile of extracts and assess the influence of extracts on the growth and adhesion of probiotics and foodborne pathogenic bacteria and on the inflammatory response of epithelial cells. Enzyme-assisted extraction altered the polyphenolic profile (as assessed by HPLC-DAD), increasing the content of aglycone flavanones (naringenin and hesperetin). Enzymatic extracts and aglycone flavanones exhibited higher antibacterial and prebiotic activities than non-enzymatic extracts and glycoside flavanones. However, a higher content of aglycones was not associated with higher anti-adhesion activity. Citrus extracts significantly (P ≤ 0.05) decreased the inflammatory response of Caco-2 cells to Salmonella Typhimurium adhesion. These results support the sustainable reuse of citrus agroindustrial wastes and indicate the potential of citrus extracts in preventing infection by foodborne pathogenic bacteria and inducing proliferation of probiotics in foods and the gut environment.

Background: Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking., Methods: Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock., Results: There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A., Conclusion: Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Bei Yin et al.)

Background: The selection of quality control indicators in a complex system is a key scientific issue for the study of Chinese materia medica (CMM), which is directly related to its safety and efficacy. In order to scientifically understand and control the quality of CMM, quality marker (Q-marker) has been recently raised as a new concept, which provided a novel research idea for the quality control and evaluation of CMM., Purpose: By a new and integrated "spider-web" mode, Q-markers of Xuefu Zhuyu capsule (XZC) were comprehensively uncovered, conducing to great improvement of quality control of XZC., Methods: Mainly established by three dimensions derived from six variables including content, stability and activity, "spider-web" mode was constructed to evaluate Q-marker property of candidate compounds by taking regression area of the tested compounds into account., Results: The candidate compounds with larger regression area were preferentially adopted as Q-markers, which should possess the satisfactorily integrated properties of content, stability and activity. Six compounds, naringin, isoliquiritin, paeoniflorin, protocatechuic acid, neohesperidin and ferulic acid, were identified and preferred as Q-markers of XZC., Conclusion: Based on "spider-web" mode, Q-markers from Xuefu Zhuyu capsule were successfully screened, which would substantially perform quality control of XZC and prove the feasibility of "spider-web" mode in solving the selection of quality control indicators from compound formulae., Competing Interests: Conflict interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)