Search Results (90)

Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used to predict potential targets related to the anti-IS effect of ISL. The binding ability of ISL to potential core targets was further analyzed by molecular docking and molecular dynamics (MD) simulations. By establishing an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cell model, the anti-IS mechanisms of ISL were investigated via RT-qPCR and Western Blot (WB). As a result, network pharmacology analysis revealed that APP, ESR1, MAO-A, PTGS2, and EGFR may be potential core targets of ISL for anti-IS treatment. Molecular docking and molecular dynamics simulation results revealed that ISL can stably bind to the five potential core targets and form stable complex systems with them. The results of the cell experiments revealed a significant anti-IS effect of ISL. Additionally, mRNA and protein expression levels of APP, MAO-A and PTGS2 or ESR1 in the ISL treatment group were significantly lower or higher than those in the OGD/R group In conclusion, ISL may improve IS by regulating the protein expression levels of APP, ESR1, MAO-A, and PTGS2. Full article

Muscle atrophy, characterized by progressive loss of skeletal muscle mass and strength, remains a significant therapeutic challenge. Jakyak-gamcho-tang (JGT) is a traditional herbal formulation that has demonstrated promising muscle-protective effects; however, the key bioactive constituents and the influence of different extraction methods have not yet been fully elucidated. This study compared the muscle-protective effects of the ethanol and water extracts of JGT (JGT-E and JGT-W, respectively), while also identifying the principal bioactive compounds that contribute to the enhanced efficacy of JGT-E. An integrative methodological approach was adopted, incorporating transcriptomic profiling, network pharmacology analysis, antioxidant activity assays, and in vitro validation using C2C12 myoblasts and myotubes. This comprehensive investigation enabled a detailed assessment of the biological activities of both JGT-E and JGT-W. Transcriptomic analysis revealed that JGT-E significantly modulates key pathways involved in oxidative phosphorylation, mitochondrial biogenesis, and signaling cascades related to PGC-1α, mTORC1, and ERRα, while simultaneously inhibiting TGF-β-mediated muscle atrophic signaling. Functional assays demonstrated that under oxidative stress conditions, JGT-E preserved mitochondrial content more effectively, reduced reactive oxygen species levels, and enhanced both myoblast viability and myotube integrity. Network pharmacology analysis identified isoliquiritigenin, catechin, and glabridin as major bioactive compounds enriched in JGT-E, all of which play critical roles in mitigating oxidative stress and supporting mitochondrial function. These findings were further substantiated by antioxidant assays that confirmed the contribution of these compounds to the observed muscle-protective effects of JGT-E. Overall, JGT-E exhibited superior efficacy in preventing muscle atrophy compared to JGT-W, likely due to its enriched profile of potent bioactive constituents. These results highlight the critical role of extraction methods in herbal medicine research and support the potential of JGT-E as a promising candidate for the treatment of muscle atrophy. Full article

Electrophilic compounds are bioactive components commonly found in foods that are capable of covalently modifying nucleophilic sites on biologically functional macromolecules. These compounds may elicit positive bioactivity or negative biotoxicity, posing significant challenges in terms of time and resource expenditure in the de novo characterization of their biological activity. In this study, we developed a database of 332 food-derived electrophilic compounds and used a semi-supervised k-nearest neighbors (KNN) machine learning model to predict their bioactivity. Molecular docking analysis identified the three chalcone compounds with the highest potential positive activity—4-hydroxyderricin (4HD), isoliquiritigenin (ISO), and butein. Furthermore, in cell experiments, treatment with 4HD, ISO, and butein significantly reduced reactive oxygen species (ROS) levels. An RT-qPCR analysis demonstrated that these chalcones significantly upregulated the mRNA expression of Nrf2 and its downstream antioxidant genes, including Nqo1, HO-1, Gsr, Gclc, and Gclm. ISO’s cytoprotective and antioxidant effects were abolished following these findings, which highlight that 4HD, ISO, and butein are effective Nrf2 activators and suggest that comprehensive virtual technology is a promising strategy for identifying functional bioactive compounds. Full article

To identify the molecular targets and possible mechanisms of isoliquiritigenin (ISO) in affecting chronic obstructive pulmonary disease (COPD) by regulating the glycolysis and phagocytosis of alveolar macrophages (AM). Datasets GSE130928 and GSE13896 were downloaded from the Gene Expression Omnibus (GEO) database. Genes related to glycolysis and phagocytosis phenotypes were obtained from the GeneCards and MSigDB databases, respectively. Weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted on GSE130928 to identify potential target genes for COPD (gene list 1). ISO target genes were gathered from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, as well as the Comparative Toxicogenomic Database (CTD) and PubChem databases (gene list 2). COPD-related targets were gathered from the CTD and GeneCards databases, and the predicted targets of COPD were obtained by taking the intersection of these sources (gene list 3). From the three gene lists, key pathways were identified. The protein–protein interaction (PPI) network was created by extracting the common genes found in all key pathways and ISO targets. Candidate therapeutic targets were identified using the Minimum Common Oncology Data Element (MCODE) algorithm. These targets were then intersected with glycolysis and phagocytic phenotype-associated genes. The resulting intersection underwent further screening using eight distinct machine learning methods to identify phenotype-related key therapeutic targets. Clinical diagnostic evaluations—including nomogram analysis, receiver operating characteristic (ROC) analysis, correlation studies, and inter-group expression comparisons—were subsequently performed on these key targets. The research findings were validated using the independent dataset GSE13896. Additionally, gene set enrichment analysis (GSEA) was conducted to explore their functional relevance. Immune cell profiling was performed using mRNA expression data from AM in COPD patients. Molecular docking was then carried out to predict interactions between ISO and the identified key target genes. Differential expression analysis and WGCNA module analysis identified a total of 890 potential targets for COPD. Additionally, 3265 predicted targets for COPD were obtained through the intersection of two disease databases. Database searches also yielded 142 targets for ISO. Enrichment analysis identified 20 key pathways, from which three key targets (AKT1, IFNG, and JUN) were ultimately selected based on their overlap with enriched genes, ISO targets, and glycolysis- and phagocytosis-related genes. They were also validated using external datasets. Further analysis of signaling pathways and immune cell profiles highlighted the influence of immune infiltration in COPD and underscored the critical role of macrophages in disease pathology. Molecular docking simulations predicted the binding interactions between ISO and the three key targets. AKT1, IFNG, and JUN may be the key targets of ISO in regulating glycolysis and phagocytosis to affect COPD. Full article

Gut bacterial β-glucuronidase is an important molecular target in several therapeutic applications. β-glucuronidase inhibitors can effectively alleviate gastrointestinal toxicity caused by certain drugs. Licorice, a traditional Chinese medicine, harmonizes various herbs and mitigates the toxicity of hundreds of herbs. In this study, a comprehensive computational strategy was employed to evaluate four licorice flavonoids (liquiritigenin, isoliquiritigenin, liquiritin, and isoliquiritin) as potential Escherichia coli β-glucuronidase (EcGUS) inhibitors. Density functional theory was used to determine their geometries, thermal parameters, dipole moments, polarizabilities, and molecular electrostatic potentials. The inhibitory mechanisms of these four flavonoids on EcGUS were investigated using molecular docking, molecular dynamics simulations, and free energy calculations. The results show that all four flavonoids stably bind to EcGUS. Moreover, all molecules, except liquiritigenin, are potent and selective inhibitors of EcGUS. Further calculations suggest that isoliquiritin exhibits the strongest binding affinity for EcGUS among the four licorice flavonoids. Thus, isoliquiritin is a promising candidate for the development of EcGUS inhibitors. These findings will aid in designing and developing novel flavonoid-based inhibitors of EcGUS to alleviate gastrointestinal toxicity caused by drugs. Full article

Brown adipose tissue (BAT) is a critical regulator of non-shivering thermogenesis and energy expenditure, offering significant potential for addressing obesity and associated metabolic disorders. Isoliquiritigenin (ISL), a natural flavonoid, has shown promising therapeutic effects in lipid metabolism-related diseases. This study aimed to explore the effects of ISL on lipid metabolism and obesity using a high-fat-diet (HFD)-induced obesity model in mice. Mice were subjected to an HFD and treated with ISL via gavage. The results demonstrated that ISL treatment significantly reduced HFD-induced weight gain and upregulated the expression of key thermogenic genes, suggesting enhanced BAT activity and thermogenesis. In vitro experiments using C3H10-T1/2 cells further supported these findings, as ISL treatment markedly increased the expression of UCP1 and PPARGC1a, which are critical regulators of thermogenesis. To elucidate the molecular mechanisms underlying ISL’s effects, we conducted a transcriptomic analysis of BAT from ISL-treated mice. Pathway enrichment analysis revealed that differentially expressed genes were predominantly associated with metabolic processes, including the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and fatty acid degradation. These pathways are integral to energy metabolism and thermogenesis, providing mechanistic insights into ISL’s anti-obesity effects. Additionally, ISL treatment significantly downregulated the expression of NNAT and SGK1, genes implicated in lipid metabolism and energy homeostasis. These findings suggest that ISL modulates BAT function by regulating the expression of these genes, thereby influencing lipid deposition and thermogenic capacity. In summary, this study suggests that ISL treatment has the potential to mitigate HFD-induced obesity by promoting BAT thermogenesis and modulating lipid metabolism. The molecular mechanisms involve the regulation of key metabolic pathways and genes, such as NNAT and SGK1, highlighting ISL’s potential as a therapeutic agent for obesity and related metabolic disorders. Full article

This article primarily develops a new technology for the rapid large-scale screening of isoliquiritigenin-transforming strains based on the MTHM (microplate reader–TLC–HPLC–UPLC-MS) method. ISO is a chalcone compound with potential pharmacological activity, and its rich substitution sites on the benzene ring provide a solid foundation for structural modification and drug development. This study screened approximately 1500 strains and employed a microplate reader, thin-layer chromatography, high-performance liquid chromatography, and mass spectrometry to verify the transformation products, identifying 15 strains with significant transformation capabilities. This study demonstrates that the optimized MTHM method is efficient and reliable, capable of rapidly detecting subtle structural changes in flavonoids before and after microbial transformation. During the transformation process, bioactive flavonoid compounds, such as amentoflavone and 5′-methoxyflavonoid, were discovered. Additionally, the experiments revealed that Czapek medium, modified Martin medium, and LB medium exhibited high efficiency in screening transforming strains. This research provides new technical approaches for ISO structural optimization and drug development while highlighting the important application potential of microbial transformation in natural product development. Future studies could further explore the metabolic potential of these strains, optimize transformation conditions, and promote the application of ISO in the medical field. Full article

This study tested the ISL against renal damage induced by a high-fat diet (HFD) and explored its underlying mechanisms. Adult male rats were assigned to four groups: (1) control on a standard diet (STD), (2) ISL on STD (30 mg/kg), (3) HFD, and (4) HFD + ISL (30 mg/kg). After 12 weeks of dietary intervention, ISL treatment led to significant reductions in body weight gain, visceral fat, and glucose and insulin levels in HFD-fed rats. Notably, ISL decreased serum urea and creatinine, increased serum albumin, and improved urinary profiles by lowering the urinary albumin and the albumin/creatinine ratio. Histological analyses revealed that ISL enhanced the glomerular structure and mitigated tubular damage, as evidenced by reduced urinary excretion of the kidney injury markers NGAL and KIM-1. Additionally, ISL significantly lowered cholesterol, triglycerides, and free fatty acids in both the control and HFD groups while also decreasing oxidized low-density lipoproteins (ox-LDLs) and malondialdehyde (MDA). Importantly, ISL enhanced renal antioxidant levels, increasing glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Moreover, ISL downregulated mRNA levels of MD-2, Toll-like receptor-4 (TLR-4), and NF-κB, leading to reduced NF-κB p65 levels in renal tissues. In conclusion, ISL offers substantial protection against HFD-induced renal toxicity through mechanisms that attenuate metabolic stress, enhance antioxidant defenses, and inhibit the MD-2/TLR4/NF-κB inflammatory pathway. Full article

Malaria remains a critical global health challenge, particularly affecting Sub-Saharan Africa. Plasmepsins, vital in hydrolyzing peptide bonds within proteins, present promising targets for antimalarial drugs. Plasmepsins I and II, key aspartic proteases, are crucial in various parasite processes. This study investigates the inhibitory properties of quercetin, quercetrin, dihydrostilbene, 4′-methoxy-isoliquiritigenin, and stigmasterol from Globimetula oreophila on plasmepsins through in silico techniques, including ADME predictions and molecular docking. Results reveal strong interactions of these compounds with active site residues, with quercetrin and stigmasterol displaying notable binding affinities. These findings suggest the potential of G. oreophila metabolites as potent plasmepsin inhibitors, offering prospects for malaria treatment and prevention. Full article

The imperative need to produce safe foodstuffs using environmentally sustainable practices has highlighted the incorporation of legumes in human and animal diets as an emerging nutritional staple. Since legumes comprise a family of plants known to display an extensive agricultural diversity with significant bioactivities, we report herein the exploitation outcome of the nutritional and bio-functional content of hay, derived from the post-harvest aerial parts of eight novel-improved Greek cultivars belonging to the following six taxa: Larthyrus sativus L., Medicago sativa L., Cicer arietinum L., Pisum sativum L., Vicia faba L., and Phaseolus vulgaris L. In specific, the phytochemical content of their hay extracts was screened against the presence of 37 fatty acids and 67 polyphenols using, respectively, GC-FID and LC-MS/MS instruments, while the determination of their total phenolic and tannin contents was achieved with spectrophotometric methods. In this respect, the presence of 26 different fatty acids was detected of which the acids linoleic, linolenic and palmitic were traced in all extracts in concentrations exceeding the 10 mg/g, while the oleic acid was determined as the major component of C. arietinum (77.58 mg/g), V. faba (36.11 mg/g), and L. sativus (12.89 mg/g) extracts. In addition, 30 different phenolics were traced as extracts’ components with the most abundant the molecule of isoquercetin, which was present in six extracts and isoliquiritigenin, calycosin, and chlorogenic acid which were detected in five extracts. Finally, the antioxidant properties of the extracts were evaluated by performing both DPPH^• and FRAP assays, which highlighted the V. faba extract as the most potent in both tests, followed by the extracts of P. sativum and P. vulgaris. Results herein are indicative of the significant advances achieved, for the improvement of investigated plant cultivars with respect to their utilization as nutritional crops, since these novel cultivars hays have been found to contain significant amounts of essential nutrients in the form of fatty acids along with bioactive ingredients in the form of polyphenols, while simultaneously they were determined as deprived of tannins that constitute essential anti-nutritional factors. Full article

A high-altitude, low-pressure hypoxic environment has severe effects on the health and work efficiency of its residents, and inadequate preventive measures and adaptive training may lead to the occurrence of AMS. Acute exposure to hypoxia conditions can have a less-favorable physiological effect on the human immune system. However, the regulation of the immune system in high-altitude environments is extremely complex and remains elusive. This study integrated system bioinformatics methods to screen for changes in immune cell subtypes and their associated targets. It also sought potential therapeutically effective natural compound candidates. The present study observed that monocytes, M1 macrophages and NK cells play a crucial role in the inflammatory response in AMS. IL15RA, CD5, TNFSF13B, IL21R, JAK2 and CXCR3 were identified as hub genes, and JAK2 was positively correlated with monocytes; TNFSF13B was positively correlated with NK cells. The natural compound monomers of jasminoidin and isoliquiritigenin exhibited good binding affinity with JAK2, while dicumarol and artemotil exhibited good binding affinity with TNFSF13B, and all are expected to become a potential therapeutic agents. Full article

Currently, clinically available cancer chemopreventive drug options are limited to mostly tamoxifen and its derivatives, such as raloxifene, and approved specifically for breast cancer. Thus, the availability of chemopreventive drug molecules for other types of malignant cancers would be desirable. In previous reports, the arils of Myristica fragrans (mace) have been found to exhibit cancer chemopreventive activity. Therefore, the purpose of the present study was to identify a natural product from this species with potential chemopreventive activity guided by chemoinformatic sample analysis via Global Natural Products Social (GNPS) molecular networking and molecular docking. The neolignan licarin A (1) was identified as a potential chemopreventive constituent, and subsequently submitted to several in vitro bioassays and a zebrafish toxicity evaluation. In this work, 1 afforded superior phosphoNF-κBp65 phosphorylation activity in DU-145 prostate cancer cells compared to isoliquiritigenin (2), which was used as a natural product chemopreventive control. Both 1 and 2 showed a longer-lasting reduction in cellular stress in a cell oxidative stress real-time dose–response assay than the positive control using Hepa1c1c7 mouse hepatoma cells. In addition, 1 displayed similar activities to 2, while also being less toxic to zebrafish (Danio rerio) than both this chalcone and the clinically used chemopreventive drug tamoxifen. 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

Camellia luteoflora is a rare and endangered plant endemic to China. It has high ornamental and potential economic and medicinal value, and is an important germplasm resource of Camellia. To understand the distributions and differences in metabolites from different parts of C. luteoflora, in this study, we used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to examine the types and contents of chemical constituents in five organs of C. luteoflora: roots, stems, leaves, flowers, and fruits. The results showed that a total of 815 metabolites were identified in the five organs and were classified into 18 main categories, including terpenoids (17.1%), amino acids (10.4%), flavonoids (10.3%), sugars and alcohols (9.8%), organic acids (9.0%), lipids (7.1%), polyphenols (4.8%), alkaloids (4.8%), etc. A total of 684 differentially expressed metabolites (DEMs) in five organs were obtained and annotated into 217 KEGG metabolic pathways, among which metabolic pathways, ABC transporters, the biosynthesis of cofactors, and the biosynthesis of amino acids were significantly enriched. In DEMs, flowers are rich in flavonoids, polyphenols, organic acids, and steroids; fruits are rich in amino acids, alkaloids, vitamins, and xanthones; stems are rich in lignans; and leaves have the highest relative content of phenylpropanoids, ketoaldehydic acids, quinones, sugars and alcohols, terpenoids, coumarins, lipids, and others; meanwhile, the metabolite content is lower in roots. Among the dominant DEMs, 58 were in roots, including arachidonic acid, lucidone, isoliquiritigenin, etc.; 75 were in flowers, including mannose, shikimic acid, d-gluconic acid, kaempferol, etc.; 45 were in the fruit, including pterostilbene, l-ascorbic acid, riboflavin, etc.; 27 were in the stems, including salicylic acid, d-(-)-quinic acid, mannitol, (-)-catechin gallate, etc.; there was a maximum number of 119 dominant metabolites in the leaves, including oleanolic acid, l-glucose, d-arabitol, eugenol, etc. In sum, the rich chemical composition of C. luteoflora and the significant differences in the relative contents of metabolites in different organs will provide theoretical references for the study of tea, flower tea, edible oil, nutraceuticals, and the medicinal components of C. luteoflora. Full article

Background/Objectives: Brazilian red propolis has attracted attention for its pharmacological properties. However, signs of toxicity were recently observed in long-term studies using the hydroalcoholic extract of red propolis (RPHE), likely due to polyprenylated benzophenones. This study aimed to develop a benzophenone-free red propolis extract (BFRP) and validate an HPLC-PDA method to quantify its main constituents: isoliquiritigenin, vestitol, neovestitol, medicarpine, and 7-O-methylvestitol. Methods: BFRP’s toxicity was assessed in zebrafish larvae through a vibrational startle response assay (VSRA) and morphological analysis. Genotoxicity was evaluated using the micronucleus test in rodents, and the extract’s effects on chemically induced preneoplastic lesions in rat colon were studied. An HPLC-PDA method was used to quantify BFRP’s main compounds. Results: BFRP primarily contained vestitol (128.24 ± 1.01 μg/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 µg/mL of BFRP exhibited toxicity, higher than the 10 µg/mL for RPHE, though no morphological differences were found. Fluorescent staining in the notochord, branchial arches, and mouth was observed in larvae treated with both BFRP and RPHE. No genotoxic or cytotoxic effects were observed up to 2000 mg/kg in rodents, with no impact on hepatotoxicity or nephrotoxicity markers. Chemoprevention studies showed a 41.6% reduction in preneoplastic lesions in rats treated with 6 mg/kg of BFRP. Conclusions: These findings indicate that BFRP is a safe, effective propolis-based extract with potential applications for human health, demonstrating reduced toxicity and chemopreventive properties. Full article