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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.

Bioactive compounds derived from natural sources have long been investigated for the prevention and treatment of human diseases. Sophoraflavanone G (SFG), a lavandulyl flavanone naturally occurring in several Sophora plant species, belongs to the group of prenylated flavonoids that have garnered significant interest in contemporary research. The natural molecule exhibits a wide range of pharmacological properties and shows remarkable efficacy. Its ability to effectively suppress a range of malignant tumor cells, such as leukemia, breast cancer, and lung cancer, is attributed to its multi-target, multi-pathway, and multi-faceted mechanisms of action. Simultaneously, it can also alleviate various inflammatory diseases by mediating inflammatory mediators and molecular pathways. Furthermore, it has the capability to combat antibiotic resistance, exhibit synergistic antibacterial properties with diverse antibiotics, and prevent and treat various agricultural pests. Theoretically, it can bring benefits to human health and has potential value as a drug. Nevertheless, the drawbacks of poor water solubility and inadequate targeting cannot be overlooked. To comprehensively assess the current research on SFG, leverage its structural advantages and pharmacological activity, overcome its low bioavailability limitations, expedite its progression into a novel therapeutic drug, and better serve the clinic, this article presents a overall retrospect of the current research status of SFG. The discussion includes an analysis of the structural characteristics, physicochemical properties, bioavailability, pharmacological activities, and structure-activity relationships of SFG, with the goal of offering valuable insights and guidance for future research endeavors in this field., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.)

Ethnopharmacological Relevance: Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated., Aim of the Study: To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action., Materials and Methods: UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds., Results: Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation., Conclusion: Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage., 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.)

Sakuranin is a flavanone which is a class of flavonoids found abundantly in Prunus species. Flavonoids have been long known for their anticancer properties against a range of human cancers. However, there are no previous reports on the anticancer effects of sakuranin flavanone molecule. This study was designed to study the anticancer effects of sakuranin against human oropharyngeal carcinoma cells along with investigating its effects on caspase-mediated apoptosis, mitochondrial membrane potential (MMP) loss, cell migration and invasion and m-TOR/PI3K/AKT signalling pathway. MTT assay was used to study effects on cell viability. The apoptotic studies were carried out through AO/EB staining, annexin V/FITC staining, comet assay and western blotting assay. Transwell chambers assay was used to study effects on cell migration and invasion. Flow cytometry was used to study effects of Sakuranin on mitochondrial membrane potential loss (MMP). Finally, western blotting was used to investigate m-TOR/PI3K/AKT signalling pathway. Results indicated that Sakuranin led to potent cell proliferation inhibition in a dose-dependent manner. Sakuranin also induced apoptotic cell death as indicated by fluorescence microscopy and annexin V/FITC staining assays. The apoptotic induction was mediated via activation of caspase-3, caspase-9, and Bax while as it led to downregulation of Bcl-2. Sakuranin also caused inhibition of cell migration and cell invasion along with causing significant decrease in MMP. Sakuranin also caused inhibition of expressions of proteins related with m-TOR/PI3K/AKT signalling pathway. In conclusion, the current findings clearly indicate anticancer effects of Sakuranin flavanone in human oropharyngeal cancer cells and are mediated via caspase activated apoptosis, inhibition of cell migration and invasion, loss of mitochondrial membrane potential and targeting m-TOR/PI3K/AKT signalling pathway.

Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

We presented a strategy utilizing 2D NMR-based metabolomic analysis of crude extracts, categorized by different pharmacological activities, to rapidly identify the primary bioactive components of TCM. It was applied to identify the potential bioactive components from Scutellaria crude extracts that exhibit anti-non-small cell lung cancer (anti-NSCLC) activity. Four Scutellaria species were chosen as the study subjects because of their close phylogenetic relationship, but their crude extracts exhibit significantly different anti-NSCLC activity. Cell proliferation assay was used to assess the anti-NSCLC activity of four species of Scutellaria. 1 H- 13 C HSQC spectra were acquired for the chemical profiling of these crude extracts. Based on the pharmacological classification (PCA, OPLS-DA and univariate hypothesis test) were performed to identify the bioactive constituents in Scutellaria associated with the anti-NSCLC activity. As a result, three compounds, baicalein, wogonin and scutellarin were identified as bioactive compounds. The anti-NSCLC activity of the three potential active compounds were further confirmed via cell proliferation assay. The mechanism of the anti-NSCLC activity by these active constituents was further explored via flow cytometry and western blot analyses. This study demonstrated 2D NMR-based metabolomic analysis of pharmacologically classified crude extracts to be an efficient approach to the identification of active components of herbal medicine., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally as "Jampu Salo" was collected on Sulawesi Island, Indonesia. It was identified as Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) and found for the first time in Sulawesi; it was previously reported only in the eastern Philippines and Borneo. A phytochemical study of S. oblanceolatum led to the isolation of three unprecedented meroterpenoids, syzygioblanes A-C ( 1 - 3 , respectively). These compounds might be biosynthesized through [4+2] cycloaddition of various germacrane-based cyclic sesquiterpenoids with the flavone desmethoxymatteucinol to form a spiro skeleton. The unique and complex structures were elucidated by microcrystal electron diffraction analysis in addition to general analytical techniques such as high-resolution mass spectrometry, various nuclear magnetic resonance methods, and infrared spectroscopy. Synchrotron X-ray diffraction and calculations of electronic circular dichroism spectra helped to determine the absolute configurations. The newly isolated compounds exhibited collateral sensitivity to more strongly inhibit the growth of a multidrug resistant tumor cell line compared to a chemosensitive tumor cell line.

Cancer is one of the most demanding domains for innovative, effective, safe, and affordable therapeutically active chemicals. The main aim of this study is to research new phytochemicals with anticancer activity. The current experiment identified and analyzed six compounds for anti-cancer potential supported by molecular simulation studies. The defatted methanolic extract underwent column chromatography, resulting in the isolation of six flavonoids. These include 3,5,7,4'-tetrahydroxy-flavanone ( 1 ), naringenin ( 2 ), 3,5,4'-trihydroxy-7-methoxy-flavanone ( 3 ), sakuranetin ( 4 ), spinacetin ( 5 ), and patuletin ( 6 ). The isolated compounds ( 1-6 ) were assessed for in vitro anti-cancer activity against various cell lines such as HepG2 (hepatoma G2), A498 (kidney), NCI-H226 (lungs), and MDR2780AD (human ovarian). The maximum antiproliferative effect was against HepG2 and MDR2780AD. When compounds 6 , 5 , and 1 were compared to a standard anti-cancer medicine (paclitaxel) with an IC 50 of 7.32, it was shown that compounds 6 , 5 , and 1 exhibited significant activity against HepG2 with IC 50 values of 14.65, 20.87, and 27.09 µM, respectively. All tested compounds showed an IC 50 of less than 1 µM and had notable effects against MDR2780 AD cell lines. Compound 6 exhibited notable potency against the HepG2, A498, and MDR2780AD cell lines, among the six compounds that were evaluated. In contrast, compound 3 demonstrated the most pronounced impact on the NCI-H226 cell line. Docking investigations were performed using tubulin as the specific target concerning PDB ID 4O2B. The six compounds under investigation interact hydrophobically and hydrophilically with tubulin-binding site amino acid residues., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

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.

Chromolaena tacotana is a source of flavonoids with antiproliferative properties in human breast cancer cells, the most common neoplasm diagnosed in patients worldwide. Until now, the mechanisms of cell death related to the antiproliferative activity of its flavonoids have not been elucidated. In this study, a novel flavanone (3',4'-dihydroxy-5,7-dimethoxy-flavanone) was isolated from the plant leaves and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS). This molecule selectively inhibited cell proliferation of triple-negative human breast cancer cell lines MDA-MB-231 and MCF-7 whit IC 50 values of 25.3 μg/mL and 20.8 μg/mL, respectively, determined by MTT assays with a selectivity index greater than 3. Early and late pro-apoptotic characteristics were observed by annexin-V/7-AAD detection, accompanied by a high percentage of the Bcl-2 anti-apoptotic protein inactivated and the activation of effector Caspase-3 and/or 7 in breast cancer cells. It was verified the decreasing of XIAP more than Bcl-2 anti-apoptotic proteins expression, as well as the XIAP/Caspase-7 and Bcl-2/Bax complexes dissociation after flavanone treatment. Docking and molecular modeling analysis between the flavanone and the antiapoptotic protein XIAP suggests that the natural compound inhibits XIAP by binding to the BIR3 domain of XIAP. In this case, we demonstrate that the new flavanone isolated from leaves of Chomolaena tacotana has a promising and selective anti-breast cancer potential that includes the induction of intrinsic apoptosis by downregulation of the anti-apoptotic proteins XIAP and Bcl-2. New studies should deepen these findings to demonstrate its potential as an anticancer agent.

Objectives: The ethyl acetate extraction of Artemisia ordosica Krasch (AOK) root showed anti-allergic rhinitis (AR) effect, while the active compounds and pharmacological targets were unknown., Methods: The P815 degranulation was established by cell counting kit 8 assay, β-hexosaminidase releasing assay and toluidine blue staining. The flavonoids were screened in vitro. Then toluidine blue staining and ELISA were carried out to investigate the anti-inflammatory effects of the active compound. Network pharmacology was implemented to explain the mechanisms of the active compound. iGEMDOCK was used to investigate the binding between active compound and hub targets., Key Findings: C48/80 was the optimum reagent in triggering P815 degranulation. Naringenin could significantly decrease P815 degranulation. Meanwhile, naringenin could remarkably increase the IL-4 and decrease the tumour necrosis factor-α. The effect of naringenin on AR was achieved by regulating multiple targets (e.g. AKT1, MAPK3, VEGFA) and pathways (e.g. pathways in cancer, VEGF signalling pathway). Nine hub proteins were obtained by topological analysis. Multiple hydrogen bonds and van der Waals forces were formed between the naringenin and the residues of hub proteins., Conclusions: Naringenin might be one of the effective ingredients of AOK against AR. And its effects could achieve through regulating multiple targets and pathways., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Huangqin decoction (HQD) is a Traditional Chinese Medicine formula for ulcerative colitis. However, the pharmacology and molecular mechanism of HQD on ulcerative colitis is still unclear. Combined microarray analysis, network pharmacology, and molecular docking for revealing the therapeutic targets and molecular mechanism of HQD against ulcerative colitis. TCMSP, DrugBank, Swiss Target Prediction were utilized to search the active components and effective targets of HQD. Ulcerative colitis effective targets were obtained by microarray data from the GEO database (GSE107499). Co-targets between HQD and ulcerative colitis are obtained by Draw Venn Diagram. PPI (Protein-protein interaction) network was constructed by the STRING database. To obtain the core target, topological analysis is exploited by Cytoscape 3.7.2. GO and KEGG enrichment pathway analysis was performed to Metascape platform, and molecular docking through Autodock Vina 1.1.2 finished. 161 active components with 486 effective targets of HQD were screened. 1542 ulcerative colitis effective targets were obtained with |Log 2 FC|> 1 and adjusted P-value < 0.05. The Venn analysis was contained 79 co-targets. Enrichment analysis showed that HQD played a role in TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, etc. IL6, TNF, IL1B, PTGS2, ESR1, and PPARG with the highest degree from PPI network were successfully docked with 19 core components of HQD, respectively. According to ZINC15 database, quercetin (ZINC4175638), baicalein (ZINC3871633), and wogonin (ZINC899093) recognized as key compounds of HQD on ulcerative colitis. PTGS2, ESR1, and PPARG are potential therapeutic targets of HQD. HQD can act on multiple targets through multi-pathway, to carry out its therapeutic role in ulcerative colitis., (© 2022. The Author(s).)

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.)

Since glucolipid metabolism disorders is often the mono-target therapy fails in managing blood glucose and lipid levels and the other complications, it is urgent and necessary to seek for the new potential drugs or functional food acting on multi-targets. The hypoglycemic and hypolipidemic dual activities of the root, stems and leaves of Desmodium caudatum, which is used for traditional Chinese medicine, was evaluated. Twelve extracts with different extraction conditions were prepared and extract 9 was find to exhibit potential inhibitory activities of fructose-1, 6-bisphosphatase (FBPase), α-glucosidase, and pancrelipase, as well as promote cellular glucose consumption and reduce cellular content of lipid. Five flavonoids were isolated and identified from extract 9, among which 8-prenylquercetin exhibited potent α-glucosidase (IC 50  = 4.38 μM) and FBPase (IC 50  = 3.62 μM) dual inhibitory activity, which were 75-fold higher than acarbose (IC 50  = 330.10 μM) and comparable with AMP (IC 50  = 2.92 μM). In addition, 8-prenylquercetin was able to promote glucose consumption and reduce lipid content. Besides, an efficient synthesis of the most potent 8-prenylquercetin was developed from inexpensive and commercially available rutin in 21% overall yield by 6 steps, which lay the foundation of preparation sufficient amount for follow-up study., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The chemical characterization study of an endemic plant, Haplanthodes neilgherryensis is (Wight) R.B. Majumdar from Western Ghats of India, resulted in to the isolation of a new flavanone glycoside, 5-hydroxy-7-methoxy-8-O- β -D-glucopyranosyl-2S-flavanone ( 1 ), along with 3 known flavonoids, 7-O-methyl dihydrowogonin ( 2 ), 7-O-methyl wogonin ( 3 ), andrographidine C ( 4 ). The structure of 1 was elucidated by using 1 D and 2 D NMR and HRMS experimental data, while for the known compounds, 1 H NMR and mass spectrometry data were compared with the reported literature. Compound 1 was tested in vitro to check the improvement in uptake of glucose by the L6 rat skeletal muscle tissues and the observed EC 50 value was 5.8 µM, while rosiglitazone showed EC 50 of 2.7 µM.

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis. Fibrosis was induced in two localized lung segments in each of the 10 sheep participating in the study. This was achieved via two infusions of bleomycin delivered bronchoscopically at a two-week interval. Another lung segment in the same sheep was left untreated, and was used as a healthy control. The animals were kept for a little over 5 weeks after the final infusion of bleomycin. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin damaged lung segments at a dose of 7 mg. This dose was given once-weekly over 4-weeks, starting one week after the final bleomycin infusion. Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of immuno-positive CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxy proline analysis showed that the administration of pinocembrin did not reduce the increased collagen content that was induced by bleomycin in this model. Analyses of Masson's Trichrome stained sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin. The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to the compound's ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: AC is the CEO of Gretals Australia Pty Ltd. Gretals Australia Pty Ltd has an interest in the development of pinocembrin for lung diseases. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Yinqin oral liquid (YOL) has curative effect for upper respiratory tract infections, especially for chronic pharyngitis (CP). Since the traditional Chinese herbal formulae are complicated, the pharmacological mechanism of YOL remains unclear. The aim of this work was to explore the active ingredients and mechanisms of YOL against CP., Methods: First, the profile of putative target of YOL was predicted based on structural and functional similarities of all available YOL components, which were obtained from the Drug Bank database, to the known drugs using TCMSP. The chemical constituents and targets of honeysuckle, scutellaria, bupleurum and cicada were searched by TCMSP, CTD, GeneCards and other databases were used to query the CP-related genes, which were searched by UniProt database. Thereafter, the interactions network between compounds and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Finally, pathway enrichment analysis of overlapping genes was carried out on Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform., Results: The pathway enrichment analysis showed 55 compounds and 113 corresponding targets in the compound-target network, and the key targets involved PTGS1, ESR2, GSK3β, NCOA2, ESR1. The PPI core network contained 30 proteins, including VEGFA, IL6, ESR1, RELA and HIF1A. A total of 148 GO items were obtained ( p <0.05), 102 entries on biological process (BP), 34 entries on biological process (BP) and 12 entries on cell composition (CC) were included. A total of 46 signaling pathways were obtained by KEGG pathway enrichment screening ( p <0.05), involving cancer, PI3K-AKT, hepatitis, proteoglycans, p53, HIF-1 signaling pathways., Conclusion: These results collectively indicate YOL (including the main ingredients luteolin and baicalein) as a highly effective therapeutic agent for anti-inflammation, through the NF-kB pathway., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Ji et al.)

Eight new complex flavanones with a novel linkage, cryptoyunnanones A-H ( 1 - 8 ), together with four known α-pyrones, were isolated from the leaves and twigs of Cryptocarya yunnanensis . The structures of 1 - 8 including their absolute configurations were characterized by spectroscopic data analysis and single-crystal X-ray crystallography. Plausible biosynthetic pathways for the formation of compounds 1 - 8 were proposed. Compounds 1 - 4 exhibited cytotoxicity against HCT-116, MDA-MB-231, and PC-3 cancer cells with IC 50 values from 6.4 to 9.1 μM.

Wogonin is one of the most active flavonoids from Scutellaria baicalensis Georgi (baikal skullcap), widely used in traditional Chinese medicine. It exhibits a broad spectrum of health-promoting and therapeutic activities. Together with baicalein, it is considered to be the one of main active ingredients of Chinese medicines for the management of COVID-19. However, therapeutic use of wogonin may be limited due to low market availability connected with its low content in baikal skullcap and lack of efficient preparative methods for obtaining this compound. Although the amount of wogonin in skullcap root often does not exceed 0.5%, this material is rich in wogonin glucuronide, which may be used as a substrate for wogonin production. In the present study, a rapid, simple, cheap and effective method of wogonin and baicalein preparation, which provides gram quantities of both flavonoids, is proposed. The obtained wogonin was used as a substrate for biotransformation. Thirty-six microorganisms were tested in screening studies. The most efficient were used in enlarged scale transformations to determine metabolism of this xenobiotic. The major phase I metabolism product was 4'-hydroxywogonin-a rare flavonoid which exhibits anticancer activity-whereas phase II metabolism products were glucosides of wogonin. The present studies complement and extend the knowledge on the effect of substitution of A- and B-ring on the regioselective glycosylation of flavonoids catalyzed by microorganisms.

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.)

An unprecedented novel flavanone davidone F ( 1 ) with a seven-membered ring side chain, and a novel flavanonol davidone G ( 2 ), along with 11 known flavonoids, were isolated from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. Their planar structures were established by UV, IR, HRESIMS, 1D and 2D NMR data. The relative configurations of 1 and 2 were determined by calculation of NMR chemical shift values, the absolute configuration of 1 and 2 were assigned by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Moreover, compounds 1 - 13 were screened for the translocation activity of glucose transporter 4 (GLUT-4), and the fluorescence intensity was increased to the range of 1.56 and 2.79 folds. Compounds 1 and 2 showed moderate GLUT-4 translocation activity with 1.64 and 1.79 folds enhancement, respectively, at a concentration of 20 μg/mL.

The bioassay-guided fractionation of a CHCl 3 -MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability ( p ≤ 0.05) by a WST-1 assay at a concentration of 100 μg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC 25 = 23 μg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated ( p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.

In this study isolates from Thymelaea hirsuta , a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound ( 1 ), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea : daphnoretin methyl ether ( 2 ), rutamontine ( 3 ), neodaphnoretin ( 4 ), acetyldaphnoretin ( 5 ), and edgeworthin ( 6 ); two flavonoids: genkwanin ( 7 ) and trans -tiliroside ( 8 ); p -hydroxy benzoic acid ( 9 ) and β sitosterol glucoside ( 10 ). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1 , 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC 50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC 50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.

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 ultrasound-assisted aqueous two-phase extraction (UA-ATPE) was first employed to develop an effective technique for simultaneous extraction and preliminary purification of synephrine, naringin, and neohesperidin from Citrus aurantium L. fruitlets. Five types of ethanol/salts of aqueous two-phase system (ATPS) were investigated and then the extraction conditions were further optimized using single-factor experiments and response surface methodology (RSM) via Box-Behnken Design (BBD). The optimum process parameters were concluded as follows: 20.60% (w/w) K 2 CO 3 , 27% (w/w) ethanol, solvent-to-material ratio of 45.17:1 (g:g), 120-mesh particle size of fruitlets powder, extraction temperature of 50 °C, extraction time of 30 min, and ultrasonic power of 80 W. Under these conditions, the extraction yields of synephrine, naringin, and neohesperidin were up to 11.17 mg/g, 7.39 mg/g, and 89.27 mg/g, respectively. The yield of neohesperidin extracted by the optimal UA-ATPE was over eight times higher than that extracted by the ultrasound-assisted extraction (UAE) using conventional solvents, and the total yield of target compounds was over twice higher while the impurity content in the extract was much lower. Therefore, UA-ATPE appeared to be a highly effective and promising approach for the extraction of synephrine, naringin, and neohesperidin from C. aurantium fruitlets.

Naringenin (1), isolated from Euphorbia pedroi, was previously derivatized yielding compounds 2-13. In this study, aiming at expanding the pool of analogues of the flavanone core towards better multidrug resistance (MDR) reversal agents, alkylation reactions and chemical modification of the carbonyl moiety was performed (15-39). Compounds structures were assigned mainly by 1D and 2D NMR experiments. Compounds 1-39 were assessed as MDR reversers, in human ABCB1-transfected mouse T-lymphoma cells, overexpressing P-glycoprotein (P-gp). The results revealed that O-methylation at C-7, together with the introduction of nitrogen atoms and aromatic moieties at C-4 or C-4', significantly improved the activity, being compounds 27 and 37 the strongest P-gp modulators and much more active than verapamil. In combination assays, synergistic interactions of selected compounds with doxorubicin substantiated the results. While molecular docking suggested that flavanone derivatives act as competitive modulators, molecular dynamics showed that dimethylation promotes binding to a modulator-binding site. Moreover, flavanones may also interact with a vicinal ATP-binding site in both nucleotide-binding domains, hypothesizing an allosteric mode of action., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Liquiritin, a flavone derived from the medicine food homology plant liquorice, possesses neuroprotective. However, the neuroprotective mechanism is not clear. In this study, metabolomics based LC-MS was performed to discover the metabolite changes in PC12 cells treated with corticosterone-induced neurotoxicity after liquiritin treatment. A total of 30 metabolites were identified as differential metabolites. Among them, 11 metabolites were regulated by liquiritin, and involved in the D-glutamine and D-glutamate metabolism, and glutathione metabolism, etc. Based on the results of metabolomics, three cell signaling pathways related to these metabolic pathways were verified. The results showed that the ERK1/2-NF-κB pathway related to the D-glutamine and D-glutamate metabolism was attenuated by liquiritin via down-regulation phospho-ERK1/2, phospho-IκBα, phospho-NF-κB protein expression levels. Furthermore, the Nrf2-Keap1 pathway related to glutathione metabolism was activated by liquiritin via up-regulation Nrf2, Keap1, HO-1, NQO1 protein expression levels, and increased SOD, CAT, GSH-PX enzyme activity, thus exerting antioxidant activity. Additionally, liquiritin inhibited the mitochondrial apoptosis by decreasing the Ca 2+ concentration, improving MMP, up-regulating Bcl-2, and down-regulating Bax, cytochrome C, cleaved-Caspase-3 expression levels. These results suggest that the neuroprotective mechanisms of liquiritin are connected to the regulation of metabolic disorders, activation Nrf2/Keap1 pathway, attenuation ERK1/2/NF-κB pathway, and inhibition mitochondrial apoptosis pathway., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

Neurodegenerative diseases (NDs) represent a global problem on public health, with a growing incidence as human longevity increases. Currently, although there are palliative strategies available for most of these diseases, there is a lack of effective therapies for their cure. Flavonoids are extensively studied for their multi-target behavior. Among numerous biological activities, it has been reported that they act at the CNS level, presenting neuroprotective activity through different mechanisms of action. Dalea L. (Fabaceae) is an American genus, with about 172 species. Dalea elegans Gillies ex. Hook. & Arn and Dalea pazensis Rusby, both South American species, are the important source of natural compounds of the prenylated flavanones type. In the present study, five prenylated flavanones isolated from Dalea species were assayed for their neuroprotective activity in two in vitro models of neurodegeneration. Flavanones 1 and 2 exhibited neuroprotective effects against oxidative stress-induced death in both models, granular cerebellar neurons and (NGF)-differentiated PC12 cells. Structure-activity relationships were also reported. Our results indicated that an 8-prenyl group at the A-ring accompanied by an unsubstituted B-ring, or a 2',4'-dihydroxy-5'-dimethylallyl substitution, lead to the most potent flavanones. Furthermore, in silico studies were performed, and several putative targets in NDs were identified for compounds 1 and 2. Between them, the enzyme acetylcholinesterase was selected for its validation in vitro. The present in vitro and in silico results imply that prenylated flavanones 1 and 2 may be useful in the development and design of future strategies for the treatment of NDs diseases., 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 Masson SAS. All rights reserved.)

Three new β-triketone flavanone hybrids, cajuputones A-C were obtained from Melaleuca cajuputi (the Australian 'tea tree'). The structures of cajuputones A-C were elucidated by 1D/2D NMR spectroscopy and HR-ESI-MS analyses; and their absolute configurations were established by electric circular dichroism (ECD) calculations using TDDFT method. Structurally, cajuputones A-C feature a rare 6/6/6/6 oxatetracyclic ring system fused between an acylphloroglucinol-derived β-triketone and a pinocembrin or strobopinin moiety via an angle-type pyran-like motif. DFT-based conformational optimization in chloroform explained the similarity of the 1D NMR data of cajuputones B and C (C-2 epimers)., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Boesenbergia rotunda (L.) Mansf. (Zingiberaceae) is an indigenous plant of Southeast Asia. Based on ethnopharmacological use, the rhizome is recommended in the treatment of stomachache, leukoplakia, abscesses, and leukorrhea in Thailand primary health care system. Candida albicans often causes leukorrhea, and infection of many mucosal sites. Its infection leads to serious illness., Aim of the Study: This study aimed to investigate the effects of the ethanolic extract of the B. rotunda rhizome on C. albicans ATCC10231 in the stages of planktonic and biofilm formation and to explore the underlying mechanisms., Materials and Methods: The chemical composition of the extract was determined using ultra-performance liquid chromatography (UPLC). The planktonic growth of C. albicans was evaluated by the microdilution method, following EUCAST guidelines. For each stage of biofilm formation, the biofilm was assessed by the MTT assay. The biofilm structure was examined under a light microscope. The degree of cell surface hydrophobicity was measured. The mRNA levels of ALS1, ALS3, and ACT1 were determined by RT-qPCR., Results: The extract of B. rotunda consisted of 25% (w/w) pinostrobin and 12% (w/w) pinocembrin. All stages of C. albicans biofilm formation were significantly inhibited by the extract, whereas the planktonic growth did not change. Biofilm development greatly decreased due to the extract in a concentration-dependent manner, with an IC 50 value of 17.7 μg/mL. Pinostrobin and pinocembrin demonstrated inhibitory effects during this stage. These results were in accordance with the microscopic evaluation. The filamentous form decreased with pinocembrin rather than pinostrobin. Moreover, the cell surface hydrophobicity was significantly decreased by 6.25 and 12.5 μg/mL of the extract and 100 μM of pinocembrin. The ALS3 mRNA level was noticeably decreased by 12.5 μg/mL of the extract, 100 μM of pinostrobin, and 100 μM of pinocembrin. The ACT1 mRNA level decreased significantly with pinocembrin. However, the ALS1 mRNA level was not altered following all treatments., Conclusion: The ethanolic extract of B. rotunda could inhibit biofilm formation of C. albicans, especially during the biofilm development stage, by means of reducing the cell surface hydrophobicity and suppressing the ALS3 mRNA expression. Pinocembrin had a stronger effect on ALS3 mRNA expression than pinostrobin. Only pinocembrin significantly decreased the ACT1 mRNA level., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S ( 1-19 ), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1 , 2 , 6 , 11 , and 18 exhibited obvious activity against α-glucosidase with IC 50 values of 5.2-9.0 μM, 20-35 times stronger than that of acarbose (IC 50 , 180.0 μM); meanwhile, 6 , 10 - 12 , and 19 were PTP1B/TCPTP-selective inhibitors with IC 50 values of 56.4-80.4 μM, 2-4 times stronger than that of suramin sodium (IC 50 , 200.5 μM). Enzyme kinetics study indicated that compounds 1 , 2 , 6 , and 11 were α-glucosidase and PTP1B mixed-type inhibitors with K i values of 13.0, 11.7, 2.9, and 5.3 μM and 142.3, 88.9, 39.2, and 40.8 μM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.

An efficient and target-oriented pH-peak-focusing countercurrent chromatographic method was established for large-scale separation of baicalin and wogonoside from the crude exact of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. An optimized two-phase solvent system composed of n-butanol-ethyl acetate-methanol-water (1:4:0.5:5, v/v) was selected. Trifluoroacetic acid (10 mmol/L) was added to the upper organic phase, used as the stationary phase. One liter of the aqueous lower phase was used as the mobile phase for 0-350 min, and then 10 mmol/L ammonia was added to remaining 1 L of the aqueous lower phase and used as the mobile phase for 350-600 min. In total, 493.2 mg of baicalin with 98.6% purity and 88.6 mg of wogonoside with 98.9% purity were obtained from 1.0 g of crude exact of S. baicalensis by countercurrent chromatography in a single run. The acid dissociation constant (pKa) and oil-water partition coefficient values of two components were measured to better understand the mechanism of separation. Results showed that pH-peak-focusing countercurrent chromatography with a polar solvent system added with trifluoroacetic acid could be an efficient method for large-scale isolation of organic acids, which are difficult to separate with conventional countercurrent chromatography due to their poor solubility in non-polar solvents., (© 2020 Wiley-VCH GmbH.)

Drug discovery from complex mixtures, like Chinese herbs, is challenging and extensive false positives make it difficult to obtain compounds with anti-Alzheimer's activity. In this study, a continuous method comprised of accelerated solvent extraction coupled with online two-dimensional countercurrent chromatography was developed for the efficient, scaled-up extraction and separation of six bioactive compounds from Citrus limon peels: neoeriocitrin, isonaringin, naringin, hesperidin, neohesperidin, and limonin. These active compounds were isolated and purified from the raw plant materials by two-dimensional countercurrent chromatography separation via two sets of an n-hexane/n-butanol/methanol/water solvent system: 0.23:1.00:0.25:1.13 and 0.47:1.00:0.38:1.46, v/v/v/v. The compounds were collected in yields of 0.22, 0.25, 0.10, 0.31, 0.29, and 0.28 mg/g, respectively, with purities of 95.79, 96.47, 97.69, 97.22, 98.11, and 98.82%, respectively. Subsequently, a simple and efficient in vitro method was developed for rapidly evaluating the acetylcholinesterase inhibitory activities of six bioactive components. Furthermore, the PC12 cell model and the in vitro metabolism of cytochromes P450 were employed to verify the monomers obtained from the continuous method. The results demonstrated that these six bioactive extracts from the C. limon peels were strong acetylcholinesterase inhibitors., (© 2020 Wiley-VCH GmbH.)

The technique of high-speed countercurrent chromatography (HSCCC) was applied to the preparative isolation and purification of liquiritin and glycyrrhizic acid from a crude extract of Glycyrrhiza uralensis Fisch for the first time. Using single factor and orthogonal design experiments, the best extraction conditions were 70% ethanol, 1:25 ratio of solid-to-liquid (w/v) and extracted 1.5 h at 80°C. The contents of liquiritin and glycyrrhizic acid in the crude extract were 1.3 and 5.3%, respectively. Using the two-phase solvent system of ethyl acetate-methanol-water (5:2:5, v/v), 6.0 mg liquiritin (the purity was 96.7%, and the recovery was 89.3%), and 20.5 mg glycyrrhizic acid (the purity was 98.9%, and the recovery was 77.1%) were obtained from 500 mg crude extraction by HSCCC, respectively. The retention rate of stationary phase was 51.0%. Their structures were identified by high-performance liquid chromatography, melting points, ultraviolet radiation, Fourier transform infrared (FTIR), Electrospray ionization mass spectrometry (ESI-MS), 1H Nuclear Magnetic Resonance (NMR) and 13C NMR spectra. The scavenging abilities of glycyrrhizic acid to 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals were stronger than those of liquiritin., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The dried roots and rhizomes of medicinal licorices are widely used worldwide as a traditional medicinal herb, which are mainly attributed to a variety of bioactive compounds that can be extracted from licorice root. Endophytes and plants form a symbiotic relationship, which is an important source of host secondary metabolites., Results: In this study, we used high-throughput sequencing technology and high-performance liquid chromatography to explore the composition and structure of the endophytic bacterial community and the content of bioactive compounds (glycyrrhizic acid, liquiritin and total flavonoids) in different species of medicinal licorices (Glycyrrhiza uralensis, Glycyrrhiza glabra, and Glycyrrhiza inflata) and in different planting years (1-3 years). Our results showed that the contents of the bioactive compounds in the roots of medicinal licorices were not affected by the species, but were significantly affected by the main effect growing year (1-3) (P < 0.05), and with a trend of stable increase in the contents observed with each growing year. In 27 samples, a total of 1,979,531 effective sequences were obtained after quality control, and 2432 effective operational taxonomic units (OTUs) were obtained at 97% identity. The phylum Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes, and the genera unified-Rhizobiaceae, Pseudomonas, Novosphingobium, and Pantoea were significantly dominant in the 27 samples. Distance-based redundancy analysis (db-RDA) showed that the content of total flavonoids explained the differences in composition and distribution of endophytic bacterial communities in roots of cultivated medicinal liquorices to the greatest extent. Total soil salt was the most important factor that significantly affected the endophytic bacterial community in soil factors, followed by ammonium nitrogen and nitrate nitrogen. Among the leaf nutrition factors, leaf water content had the most significant effect on the endophytic bacterial community, followed by total phosphorus and total potassium., Conclusions: This study not only provides information on the composition and distribution of endophytic bacteria in the roots of medicinal licorices, but also reveals the influence of abiotic factors on the community of endophytic bacteria and bioactive compounds, which provides a reference for improving the quality of licorice.

A nanoliquid chromatographic method for the stereoisomer separation of some flavanone aglycones and 7-O-glycosides has been proposed employing a C18 capillary column and a chiral mobile-phase additive such as cyclodextrin. The chiral separation of eriodictyol, naringenin, and hesperitin was obtained by addition of carboxymethyl-β-cyclodextrin to the mobile phase, whereas eriocitrin, naringin, narirutin, and hesperidin diastereoisomers were resolved by using sulfobutyl ether-β-cyclodextrin. The influence of the composition of the mobile phase, the length of the capillary column, and the flow rate on the chiral recognition were investigated. At optimum conditions, baseline separation for the selected aglycones and glycosylated forms were achieved with a mobile phase consisting of 50 mM sodium acetate buffer pH 3 and 30% methanol containing 20 mM of carboxymethyl-β-cyclodextrin and 10 mM of sulfobutyl ether-β-cyclodextrin, respectively. Precision, linearity, and sensitivity of the method were tested. Limits of detection and quantification for the studied flavanone glycosides were in the range 1.3-2.5 and 7.5-12.5 µg/mL, respectively. The method was used for the determination of the diastereomeric composition of the flavanone-7-O-glycosides in Citrus juices after solid-phase extraction procedure., (© 2020 Wiley-VCH GmbH.)

Sorghum halepense L (Poaceae), ordinarily it is known as Johnson grass and locally as baru. This study was designed to find the vascular mechanisms underlying the hypotensive activity of S. halepense. In this study, effect of S. halepense seed extract/fractions on various blood pressure parameters were evaluated in normal and fructose induced hypertensive rats by invasive technique. Possible underlying hypotensive mechanism of active fraction was determined by using various pharmacological inhibitors. S. halepense extract/fractions vasorelaxant effect were also evaluated on rat aorta rings in organ bath and various intracellular signaling pathway inhibitors were used for determination of underlying mechanisms. S. halepense extract/fractions produced blood pressure lowering effect with most significant effect by its aqueous soluble fraction at dose of 10mg/kg. This effect was attenuated by pretreatment of atropine. Aqueous soluble fraction produced endothelium dependent vasorelaxation in rat aortic rings that was inhibited by pretreatment of atropine after phenylephrine induced contraction. The vasorelaxant effect of aqueous soluble fraction was attenuated by potassium channel blockers and also produced inhibitory effect on calcium entry through calcium channels. It also suppressed phenylephrine induced contraction like verapamil. By HPLC analysis found vanillic acid and naringinin in it. In conclusion, aqueous soluble fraction of S.halepense possess phytoconstituents which may be responsible for hypotensive and vasorelaxant effect of Sorghum halepense.

Eight compounds were isolated from the roots of Glycyrrhiza uralensis and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. The coumarin glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC 50 values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC 50 = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC 50 = 0.098 µM) and MAO-A (IC 50 = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (>40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a K i value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a K i value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (-7.8 kcal/mol) was greater than its affinity for AChE (-7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (-8.8 kcal/mol) was greater than its affinity for MAO-A (-7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer's disease with multi-targeting activities.

Phytochemical reinvestigation on the whole plants of Derris laxiflora Benth. afforded two new diprenylated flavanones, derriflavanones B and C ( 1 - 2 ), together with thirty-two known compounds, including sixteen flavonoids ( 3 - 18 ), eleven aromatic compounds ( 19 - 29 ), and five chlorophylls ( 30 - 34 ). All known compounds were first isolated from this plant. The structures of these compounds were determined by analysis of the NMR spectroscopy, mass data, IR spectra, UV spectra, optical rotation and by comparison with literature data.

Ethnopharmacological Relevance: Licorice is an ancient food and medicinal plant. Liquiritigenin and liquiritin, two kinds of major flavonoes in licorice, are effective substances used as antioxidant, anti-inflammatory and tumor-suppressive food, cosmetics or medicines. However, their in vivo metabolites have not been fully explored., Aim of Study: To clarify the metabolism of liquiritigenin and liquiritin in mice., Materials and Methods: In this study, we developed a liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry approach to determine the metabolites in mice plasma, bile, urine and feces after oral administration of liquiritigenin or liquiritin. The structures of those metabolites were tentatively identified according to their fragment pathways, accurate masses, characteristic product ions, metabolism laws or reference standard matching., Results: A total of 26 and 24 metabolites of liquiritigenin or liquiritin were respectively identified. The products related with apigenin, luteolin or quercetin were the major metabolites of liquiritigenin or liquiritin in mice. Seven main metabolic pathways including (de)hydrogenation, (de)hydroxylation, (de)glycosylation, (de)methoxylation, acetylation, glucuronidation and sulfation were summarized to tentatively explain their biotransformation., Conclusion: This study not only can provide the evidence for in vivo metabolites and pharmacokinetic mechanism of liquiritigenin and liquiritin, but also may lay the foundation for further development and utilization of liquiritigenin, liquiritin and then licorice., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Beer is a fermented beverage with beneficial phenolic compounds and is widely consumed worldwide. The current study aimed to describe the content of three families of phenolic compounds with relevant biological activities: prenylated flavonoids (from hops), simple phenolic alcohols (from fermentation) and alkylresorcinols (from cereals) in a large sample of beers ( n = 45). The prenylated flavonoids analyzed were xanthohumol, isoxanthohumol, 6- and 8-prenylnaringenin. The total prenylated flavonoids present in beer ranged from 0.0 to 9.5 mg/L. The simple phenolic alcohols analyzed were tyrosol and hydroxytyrosol, ranging from 0.2 to 44.4 and 0.0 to 0.1 mg/L, respectively. Our study describes, for the first time, the presence of low amounts of alkylresorcinols in beer, in concentrations ranging from 0.02 to 11.0 µg/L. The results in non-alcoholic beer and the differences observed in the phenolic composition among different beer types and styles highlight the importance of the starting materials and the brewing process (especially fermentation) on the final phenolic composition of beer. In conclusion, beer represents a source of phenolic compounds in the diet that could act synergistically, triggering beneficial health effects in the context of its moderate consumption.

A large number of biologically active compounds are present in ripe citrus fruits. However, few studies have been focused on the changes in flavonoids and the evolution of antioxidant activity during citrus fruit growth. In this study, fruits of five citrus cultivars cultivated in China were sampled at 60-210 days post-anthesis (DPA) at intervals of 30 days. The amounts of main flavonoids in the peel and pulp were analyzed by HPLC and their activities were studied by DPPH, ABTS and FRAP. The results showed that the contents of hesperidin, diosmin, eriodictyol, rutin and nobiletin increased before 90 DPA and then decreased with the growth and development of fruits, but an opposite tendency was observed for naringin and narirutin. The antioxidant activities in citrus peel and pulp were found to be significantly correlated with some flavonoids. The results may be of guiding values in citrus production and utilization of citrus fruit by-products., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

The objective of this paper was to develop a preparative method for the isolation and purification of liquiritigenin and glycyrrhetic acid from Glycyrrhiza uralensis Fisch using hydrolytic extraction combined with high-speed countercurrent chromatography (HSCCC). Liquiritigenin and glycyrrhetic acid were well hydrolyzed from liquiritin and glycyrrhizic acid by hydrochloric acid, respectively. The optimal extraction conditions were obtained by single-factor and orthogonal experiments, which were 100% ethanol, 1.5 mol/L hydrochloric acid, 1:25 ratio of solid to liquid, and extracted 2 h for one time. Using the two-phase solvent system of n-hexane-ethyl acetate-methanol-water (4:5:4:5, v/v), 2.1 mg liquiritigenin (the purity was 96.5% with a recovery of 87.6%) and 12.3 mg glycyrrhetic acid (the purity was 97.1% with a recovery of 74.4%) were obtained from 315-mg crude extraction by HSCCC. The retention ratio of stationary phase was 47.2%. Their structures were identified by HPLC, melting points, UV, Fourier-transform infrared, Electrospray ionization-MS, 1 H nuclear magnetic resonance (NMR), and 13 C NMR spectra. According to the antioxidant activity assays, liquiritigenin and glycyrrhetic acid had some scavenging abilities on 1,1-diphenyl-2-picrylhydrazyl free radicals; liquiritigenin had stronger scavenging ability on hydroxyl radicals., (© 2020 John Wiley & Sons, Ltd.)

As a Turkish traditional medicinal plant, aerial parts of Lotus corniculatus L. subsp. corniculatus (Fabaceae) are used as a painkiller, antihemoroidal, diuretic and sedative. In this study, the antidepressant potential of the plant has been attempted to clarify. Extracts with water, n -Hexane, ethyl acetate, and methanol were prepared respectively from the aerial parts. Antidepressant activity of the extracts were researched by using three different in vivo test models namely a tail suspension test, antagonism of tetrabenazine-induced hypothermia, ptosis, and suppression of locomotor activity and forced swimming test on male BALB/c mice and in vitro monoamine oxidase (MAO)-A and B inhibition assays. The results were evaluated through comparing with control and reference groups, and then active compounds of the active extract have been determined. Bioassay-guided fractionation of active fraction led to the isolation of three compounds and structures of the compounds were elucidated by spectroscopic methods. The data of this study demonstrate that the MeOH extract of the aerial parts of the plant showed remarkable in vivo antidepressant effect and the isolated compounds medicarpin-3- O -glucoside, gossypetin-3- O -glucoside and naringenin-7- O -glucoside (prunin) from the active sub-fractions could be responsible for the activity. Further mechanistic and toxicity studies are planned to develop new antidepressant-acting drugs.

A novel benzofuranone unprecedentedly with a prenyl group at C-3, nigranol A ( 1 ), a new flavonol, nigranol B ( 2 ), and three known compounds, sanggenon M ( 3 ), nigrasin C ( 4 ), and nigrasin A ( 5 ) were isolated from the twigs of Morus nigra Linn. Their structures were elucidated on the basis of the analysis of multiple spectroscopic data. All of the compounds, along with eight previously isolated ones ( 6 - 13 ) were investigated for their α-glucosidase inhibitory activities. The result showed that compounds 1 - 13 except 4 exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 2 and 7 were the best α-glucosidase inhibitory candidates with IC 50 values at 1.63 and 1.43 μM, respectively. Furthermore, the structure-activity relationships of the sanggenon-type flavanones were summarized.

Naringin is a type of bioflavonoid widely found in a lot of dietary products. Our previous studies revealed that naringin was practically non-toxic for SD rats in an oral acute toxicity study and the no-observed-adverse-effect-level (NOAEL) in SD rats was greater than 1250 mg/kg/day when administered by oral gavage for 13 consecutive weeks or 6 consecutive months. Herein we assessed the safety of naringin in Beagle dogs. Acute oral administration of naringin was done as a single bolus dose up to 5 g/kg. Subchronic toxicity study for 3 months and chronic toxicity study for 6 months were done by oral administration at doses of 0 (control), 20, 100, and 500 mg/kg. The LD 50 dosage level for dogs was determined to be > 5 g/kg body weight. In the repeated-dose 3-month and 6-month oral toxicity studies, no morbidity, mortality, and toxicologically relevant events were observed either during dosing or the post-dosing recovery period. It was concluded that the NOAEL of naringin in Beagle dogs is at least 500 mg/kg body weight per day when administered orally for 3 and 6 consecutive months. These results, combined with the previous toxicological studies in rats, demonstrate a good safety profile of naringin., 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 Inc. All rights reserved.)

Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7- O - β -d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders.