Search Results (75)

Biflavonoids are a unique subclass of dietary polyphenolic compounds known for their diverse bioactivities. Despite these benefits, these biflavonoids remain largely underexplored due to their limited natural availability and harsh conditions required for their synthesis, which restricts broader research and application in functional foods and nutraceuticals. To address this gap, we synthesized a library of rare biflavonoids using a radical–nucleophile coupling reaction previously reported by our group. The food grade coupling reaction under weakly alkaline water at room temperature led to isolation of 28 heterocoupled biflavones from 11 monomers, namely 3′,4′-dihydroxyflavone, 5,3′,4′-trihydroxyflavone, 6,3′,4′-trihydroxyflavone, 7,3′,4′-trihydroxyflavone, diosmetin, chrysin, acacetin, genistein, biochanin A, and wogonin. The structures of the dimers are characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectroscopy (HRMS). In addition, we evaluated the antioxidant potential of these biflavones using a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay and the DPPH value ranges between 0.75 to 1.82 mM of Trolox/mM of sample across the 28 synthesized dimers. Additionally, a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis was conducted to identify structural features associated with enhanced antioxidant activity. The partial least squares (PLS) regression QSAR model showed acceptable r² = 0.936 and q² = 0.869. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), Fukui index (F-), and electron density (ED) were determined to identify the key structural moiety that was capable of donating electrons to neutralize reactive oxygen species. Full article

Background: Pulmonary hypertension (PH) remains a life-threatening rare disease characterized by inflammation and oxidative stress in pulmonary artery smooth muscle cells (PASMCs). Wogonin (Wog), a plant-derived polyphenolic compound extracted from Scutellaria baicalensis Georgi, exhibits notable antioxidant activity and anti-PH efficacy, whereas its clinical applications are greatly limited by poor aqueous solubility. Methods: Herein, an innovative wogonin-aloperine co-amorphous (Wog-Alop) was developed to improve the aqueous solubility and, thus, anti-PH efficacy of Wog. Results: As expected, the aqueous solubility of Wog-Alop is about 40-fold that of Wog; meanwhile, the Wog-Alop demonstrates better oral bioavailability and anti-PH efficacy than Wog; moreover, the Wog-Alop exhibits significantly enhanced capacity to attenuate oxidative stress in human PASMCs compared to Wog. Conclusions: The results suggested that Wog-Alop could not only improve the solubility of Wog, thereby enhancing its oral bioavailability but also alleviate Wog’s oxidative stress effects. These synergistic effects ultimately culminate in the enhanced anti-PH efficacy of Wog. In summary, the present study developed an innovative co-amorphous strategy for the delivery of Wog and improved its anti-PH efficacy. Full article

Concerns over vaccine safety, bacterial resistance, and drug residues have led to increased interest in plant extracts for improving swine nutrition and health. Scutellaria baicalensis Georgi, rich in four primary flavonoids—baicalin, baicalein, wogonoside, and wogonin—demonstrates significant pharmacological properties, including anti-inflammatory, antioxidant, antibacterial, and antiviral activities in swine. These flavonoids have been shown to enhance growth performance, improve immunity, modulate gut microbiota, and aid in the prevention and treatment of various diseases. This review highlights the pharmacological effects of these flavonoids in swine, with a focus on network pharmacology to reveal the underlying molecular mechanisms. By constructing drug-target networks and identifying key signaling pathways, the review reveals how these flavonoids interact with biological systems to promote health. Furthermore, it discusses the practical applications of Scutellaria baicalensis flavonoids in swine production and outlines potential future research directions. This work provides a theoretical framework for understanding the therapeutic targets of these flavonoids, offering valuable insights for advancing sustainable and healthy pig farming practices. Full article

Background: Yupingfeng San (YPFS) is a classic formula for treating allergic rhinitis (AR), which is composed of Astragalus mongholicus Bunge (AST), Atractylodes macrocephala Koidz (AMR), and Saposhni-kovia divaricata (Turcz.) Schischk (SR) at a ratio of 3:1:1. However, the potential bioactive components of YPFS relevant to AR treatment are currently unknown. Methods: This study combined in vivo chemical profiling, network pharmacology, and experimental validation to identify the substances in YPFS that are active against AR. Results: Firstly, 98 compounds in YPFS were identified using high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) with the assistance of Global Natural Products Social (GNPS) molecular networking. Then, 42 prototype components and 57 metabolites were detected in the plasma, urine, and feces of mice with AR. A network pharmacological analysis based on 42 in vivo prototypical components was also conducted to screen 15 key components and 10 core targets, and 6 key components were further selected through molecular docking. Finally, the four key active components (cimifugin, wogonin, formononetin, and atractylenolide I) were revealed to be the main ingredients of YPFS through validation (in vitro and in vivo). Conclusions: This is the first systematic study of the components of YPFS in AR mice, laying the foundation for elucidating the overall material basis of this formulation. This study provides rich basic data for further pharmacological and mechanistic studies on YPFS. Full article

Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: Curcuma longa, Astragalus membranaceus, Glycyrrhiza glabra, Althaea officinalis, Echinacea purpurea, Sanguinaria canadensis, Codonopsis pilosula, Hydrastis canadensis, Lobelia inflata, Scutellaria baicalensis, and Zingiber officinale. These plants were selected based on their documented use in traditional medicine and modern clinical practice. Selection criteria involved cross-referencing herbs identified in a scoping review of traditional cancer treatments and findings from an international survey on herbal medicine currently used for lung and colorectal cancer management by our research group and the availability of existing literature on their anticancer properties. The review identifies several isolated phytoconstituents from these plants that exhibit anticancer properties by modulating key signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, and TGF-β in vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric acid, glycyrrhizin, 18-β-glycyrrhetinic acid, astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, and glycyrol. Curcumin and baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome by combining them with piperine or using oral extracts to enhance gut microbiome conversion, integrating traditional knowledge with modern strategies for improved outcomes. Furthermore, herbal extracts from Echinacea, Glycyrrhiza, and Codonopsis, identified in traditional knowledge, are currently in clinical trials. Notably, curcumin and baicalin also modulate miRNA pathways, highlighting a promising intersection of modern science and traditional medicine. Thus, the development of anticancer therapeutics continues to benefit from the synergy of traditional knowledge, scientific innovation, and technological advancements. Full article

This study aims to explore the effect of pulsed electric field (PEF) treatment as a method very likely to result in reversible electroporation of Scutellaria baicalensis Georgi underground organs, resulting in increased mass transfer and secondary metabolites leakage. PEF treatment with previously established empirically tailored parameters [E = 0.3 kV/cm (U = 3 kV, d = 10 cm), t = 50 µs, N = 33 f = 1 Hz] was applied 1–3 times to S. baicalensis roots submerged in four different Natural Deep Eutectic Solvents (NADES) media (1—choline chloride/xylose (1:2) + 30% water, 2—choline chloride/glucose (1:2) + 30% water, 3—choline chloride/ethylene glycol (1:2), and 4—tap water (EC = 0.7 mS/cm). Confocal microscopy was utilized to visualize the impact of PEF treatment on the root cells in situ. As a result of plant cell membrane permeabilization, an extract containing major active metabolites was successfully acquired in most media, achieving the best results using medium 1 and repeating the PEF treatment twice (baicalein <LOQ, baicalin 12.85 µg/mL, wogonin 2.15 µg/mL, and wogonoside 3.01 µg/mL). Wogonin concentration in NADES media was on par with the control (plants harvested on the day of the experiment, ultrasound-mediated methanolic extraction, C_wogonin = 2.15 µg/mL). After successful extraction, PEF treatment allowed the plants to continue growing, with the lowest survival rate across treated groups being 60%. Additionally, an enhancement in plant growth parameters (length and fresh mass of the roots) and significant changes in the S. baicalensis root phytochemical profile were also observed. Full article

Scutellaria baicalensis Georgi is a valuable medicinal plant of the Lamiaceae family. Its roots have been used in Traditional Chinese Medicine (under the name Huang-qin) since antiquity and are nowadays included in Chinese and European Pharmacopoeias. It is abundant in bioactive compounds which constitute up to 20% of dried root mass. These substances are lipophilic flavones with unsubstituted B-ring, baicalein, and wogonin and their respective glucuronides–baicalin and wogonoside being the most abundant. The content of these compounds is variable and the environmental factors causing this remain partially unknown. The role of these compounds in stress response is still being investigated and in our efforts to measure the effect of NaCl treatment on S. baicalensis growth and metabolic profile, we hope to contribute to this research. Short-term exposure to salt stress (50, 100, and 150 mM NaCl) resulted in a marked increase of baicalein from 1.55 mg to 2.55 mg/g DM (1.6-fold), baicalin from 8.2 mg to 14.7 mg (1.8-fold), wogonin from 4.9 to 6.8 (1.4-fold), and wogonoside from 3.3 to 6.8 mg/g DM (2-fold) in the roots. Conversely, in the aerial parts, the content of individual major flavonoids: carthamidine-7-O-glucuronide and scutellarein-7-O-glucuronide decreased the most by 10–50% from 18.6 mg to 11.3 mg/g (1.6-fold less) and from 6.5 mg to 3.4 mg/g DM (0.52-fold less), respectively. The amino acid profile was also altered with an increase in root concentrations of the following amino acids: arginine from 0.19 to 0.33 mg/g (1.7-fold), glutamate from 0.09 to 0.16 mg/g DM (1.6-fold), alanine from 0.009 to 0.06 mg/g (6.8-fold), proline from 0.011 to 0.029 (2.4-fold) and lysine from 0.016 to 0.063 mg/g (3.9-fold). Aspartate concentration decreased from 0.01 to 0.002 mg/g (4.8-fold less) at 150 mM NaCl. In the aerial parts, the concentration and variation in levels of specific amino acids differed among groups. For instance, the glutamate content exhibited a significant increase exclusively in the treatment group, rising from 0.031 to 0.034 mg/g, representing a 1.2-fold increase. Proline concentration showed a marked increase across all treated groups with the highest from 0.011 to 0.11 mg/g (10-fold). In conclusion, moderate salt stress was shown to increase S. baicalensis root biomass and flavonoid content which is rarely observed in a glycophyte species and provides a foundation for further studies on the mechanisms of osmotic stress adaptation on the specialized metabolism level. Full article

Elsholtzia splendens Nakai ex F. Maek. has been employed in traditional Chinese medicine for millennia. Nevertheless, the small size and the paucity of research on its pharmacological effects have restricted its extensive utilisation in clinical medicine. Polyploid breeding represents an effective method for the rapid enhancement of plant biomass and metabolites. In this study, the most effective in vitro method for inducing tetraploid formation was identified as axillary buds treated in a solution of colchicine at a concentration of 1% for 24 h. Meanwhile, a comparison between tetraploids and diploids yielded two significant findings: (1) The presence of 6-zonocolpate and 8-zonocolpate pollen grains can be used as distinguishing characteristics for diploid and tetraploid, respectively. (2) Genome duplication resulted in alterations to the polyphenol species and synthesis pathway in E. splendens. The accumulation of wogonin, oroxylin A, baicalin, chrysin, acacetin and related derivatives was markedly greater in tetraploid plants, whereas apigenin, naringenin, scutellarein and related derivatives were found to accumulate to a greater extent in diploid plants. It is noteworthy that wogonin and oroxylin A were uniquely detected in tetraploids, indicating that the generated tetraploids may harbor novel pharmacological value. The findings not only provided new insights into the metabolic mechanism of polyploidisation but also established a foundation for the selection and breeding of novel genetic resources of E. splendens. Full article

Postharvest grapes exhibit a limited shelf life due to susceptibility to rot and deterioration, significantly reducing their nutritional and economic value. Sulfur dioxide (SO₂) is a widely recognized preservative for extending grape storage life. This study performed a detailed analysis of ‘Munage’ table grapes treated with SO₂ fumigation, employing transcriptomic and metabolomic approaches. Results indicate that SO₂ fumigation significantly extends the shelf life of grapes, as demonstrated by improved visual quality, reduced decay rates, and increased fruit firmness. We identified 309 differentially accumulated metabolites (DAMs) and 1906 differentially expressed genes (DEGs), including 135 transcription factors (TFs). Both DEGs and DAMs showed significant enrichment of flavonoid-related metabolism compared with the control, and the relative content of four flavonoid metabolites (Wogonin-7-O-glucuronide, Acacetin-7-O-glucuronide, Apigenin-7-O-glucuronide, and Baicalein 7-O-glucuronide) were significantly increased in grapes upon SO₂ treatment, suggesting that SO₂ treatment had a substantial regulatory effect on grape flavonoid metabolism. Importantly, we constructed complex regulatory networks by screening key enzyme genes (e.g., PAL, 4CLs, CHS, CHI2, and UGT88F3) related to the metabolism of target flavonoid, as well as potential regulatory transcription factors (TFs). Overall, our findings offer new insights into the regulatory mechanisms by which SO₂ maintains the postharvest quality of table grapes. Full article

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, with aldose reductase playing a critical role in the pathophysiology of diabetic complications. This study aimed to investigate the efficacy of flavonoid compounds as potential aldose reductase inhibitors using a combination of molecular docking and molecular dynamics (MD) simulations. The three-dimensional structures of representative flavonoid compounds were obtained from PubChem, minimized, and docked against aldose reductase using Discovery Studio’s CDocker module. The top 10 compounds Daidzein, Quercetin, Kaempferol, Butin, Genistein, Sterubin, Baicalein, Pulchellidin, Wogonin, and Biochanin_A were selected based on their lowest docking energy values for further analysis. Subsequent MD simulations over 100 ns revealed that Daidzein and Quercetin maintained the highest stability, forming multiple conventional hydrogen bonds and strong hydrophobic interactions, consistent with their favorable interaction energies and stable RMSD values. Comparative analysis of hydrogen bond interactions and RMSD profiles underscored the ligand stability. MMPBSA analysis further confirmed the significant binding affinities of Daidzein and Quercetin, highlighting their potential as aldose reductase inhibitors. This study highlights the potential of flavonoids as aldose reductase inhibitors, offering insights into their binding interactions and stability, which could contribute to developing novel therapeutics for DM complications. Full article

To date, no study has focused on Uvaria macrophylla leaves with various traditional efficiencies. This paper therefore applied a database affinity ultra-high-performance liquid chromatography with quadrupole Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) strategy to analyze the lyophilized aqueous extract of U. macrophylla leaves. Through database comparison and MS fragment elucidation, this study has putatively identified 41 constituents belonging to flavonoid, phenolic acid, steroid, and saccharide natural product classifications. Significantly, four groups of isomers (liquiritigenin vs. isoliquiritigenin vs. pinocembrin; oroxylin A vs. wogonin vs. galangin 3-methyl ether; isoquercitrin vs. hyperoside; protocatechuic acid vs. 2,5-dihydroxybenzoic acid) have been successfully distinguished from each other. All of 41 constituents were then subjected to a quantitative analysis based on linear regression equation established by the above UHPLC-Q-Orbitrap-MS/MS strategy and an ABTS^+•-scavenging antioxidant assay. Finally, the chemical content was multiplied by the corresponding ABTS^+•-scavenging percentage to calculate the antioxidant contribution. It was shown that the chemical contents of 41 constituents varied from 0.003 ± 0.000 to 14.418 ± 1.041 mg/g, and gallic acid showed the highest antioxidant contribution. Gallic acid is considered as a suitable antioxidant quality-marker (Q-marker) of U. macrophylla leaves. These findings have scientific implications for the resource development and quality control of U. macrophylla leaves. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive forms of pancreatic cancer with a poor prognosis. YAP1 expression is markedly elevated in PDAC, but how it works is not clear. GL-V9, a derivative of the natural compound wogonin, effectively fights a variety of tumors; however, its effect on PDAC has not yet been studied. Methods: TCGA database analysis, Western blots, immunofluorescence, and real-time PCR were used to evaluate GL-V9’s effect on YAP1 expression and mRNA levels. Immunofluorescence was used to examine the co-location of YAP1 with LAMP2 and p62. Co-immunoprecipitation was used to assess the binding of YAP1 to ubiquitin, p62, and TEAD1. A PDAC graft tumor model was used to test GL-V9’s pharmacological effects. Western blots and immunohistochemistry were used to measure apoptosis- and autophagy-related protein expression. Results: GL-V9 effectively promoted the degradation of YAP1, reduced YAP1 nuclear localization, and induced mitochondrial apoptosis in PDAC cells. YAP1 overexpression led to the upregulation of Bcl-2 and attenuated the caspase cascade induced by GL-V9. Furthermore, we demonstrated that GL-V9 induced autophagosome–lysosome fusion via the AKT/mTOR/TFEB pathway, leading to mitochondrial apoptosis in PDAC cells. In vivo studies also confirmed that GL-V9 exerts anti-tumor effects by suppressing YAP1 expression, while also activating autophagy and inducing mitochondrial apoptosis in BXPC-3-bearing BALB/c nude mice. Conclusions: Our findings underscore the importance of autophagy-mediated YAP1 degradation in PDAC, providing a novel molecular rationale (GL-V9) as a promising treatment for this disease. Full article

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. Full article

Fuzheng Xiaozheng prescription (FZXZP) is an effective formula for the treatment of different kinds of chronic liver diseases. However, its potential molecular mechanisms in treating hepatocellular carcinoma (HCC) have not been investigated thoroughly. The aim of this study is to elucidate the targets and intrinsic mechanisms of FZXZP and their active components for the treatment of HCC. The efficacy of FZXZP against HCC was clarified through a rat HCC model and HCC cell culture. Network pharmacology and molecular docking were utilized to predict the mechanism of action and effector components of FZXZP. The key mechanism and targets were verified by the construction of overexpression and knockout cell models. The results showed that FZXZP greatly delayed the development of HCC in vivo experiments, as evidenced by biochemical evaluations, H&E analyses and growth inhibition of HCC. FZXZP dramatically inhibited cell viability and proliferative capacity and induced the apoptosis of hepatoma cells in vitro. Moreover, network pharmacology analyses demonstrated that the EGFR family and apoptosis-related targets were found to be the most significant in bioinformatics analysis. Furthermore, the EGFR/STAT3 signal axis might be the most likely target of FZXZP in anti-HCC due to the fact that it could be down-regulated by FZXZP with an upward trend of Bax, Caspase-3, Caspase-8, Caspase-9 and an inverse trend of Bcl2. Importantly, the above targeted signal axis was finally validated by our knockdown and overexpression analyses. Meanwhile, flow cytometry and TUNEL staining also revealed that FZXZP significantly induced apoptosis in the EGFR-overexpressing HCC cell line. The molecular docking results revealed that the key effector components of FZXZP that exerted the above regulatory roles were wogonin and glycitein. All of these results suggest that FZXZP could significantly delay HCC development by inhibiting proliferation and promoting apoptosis of HCC cells, and the EGFR/STAT3 signal axis might be a critical signal axis of FZXZP in suppressing HCC progression. Full article

NIBV is an acute and highly contagious virus that has a major impact on the poultry industry. Wogonin, as a flavonoid drug, has antiviral effects, but there have been no reports indicating its role in renal injury caused by NIBV infection. The aim of this study is to investigate the antiviral effect of wogonin against NIBV. Renal tubular epithelial cells were isolated and cultured, and divided into four groups: Con, Con+Wog, NIBV and NIBV+Wog. We found that wogonin significantly inhibited the copy number of NIBV and significantly alleviated NIBV-induced cell apoptosis and necrosis. Moreover, wogonin inhibited the reduction in mitochondrial membrane potential and the aberrant opening of mPTP caused by NIBV. In conclusion, wogonin can protect renal tubular epithelial cells from damage by inhibiting the replication of NIBV and preventing mitochondrial apoptosis and necroptosis induced by NIBV. Full article