Search Results (11)

Leaves from California yerba santa (Eriodictyon californicum) have been used historically by indigenous peoples for medicinal purposes. Recent research has ascribed potential pharmaceutical effects to leaf polyphenols, without a consideration of other constituents. Based on prior analyses of polyphenols in leaves sampled in nature, five accessions known to be rich in sterubin and five accessions known to be rich in eriolic acid C were grown from seeds in Ontario, Oregon, and samples of their leaves were harvested and evaluated for their essential oil and polyphenol contents. The major essential oil components in E. californicum were 1,8-cineole (0.6–35.5%), (Z)-β-ocimene (6.8–15.7%), terpinen-4-ol (8.3–16.1%), α-pinene (2.6–13.6%), β-phellandrene (1.9–11.7%), γ-terpinene (4.6–7.9%), ethyl (E)-cinnamate (0.2–8.9%), α-terpineol (1.5–5.2%), p-cymene (2.0–5.3%), and β-pinene (0.6–6.8%). Fifteen polyphenols with a prominence of eriolic acid C, rosmarinic acid, sterubin, homoeriodictyol, 6-methoxynaringenin, hesperetin, and eriodictyol were identified. Essential oils may contribute to the medicinal properties of the leaves of California yerba santa. Results from the ten samples were evaluated for both polyphenols and essential oils; the variations in several essential oils may be correlated to variations in some of the polyphenols. Full article

The limited selectivity of most catalytic-site ADAMTS-5 inhibitors and the necessity to preserve aggrecan integrity in early-grade knee osteoarthritis require the development of selective aggrecanase inhibitors. The present study conducted rational in silico screening of flavonoids as potential ADAMTS-5 inhibitors by integrating high-throughput virtual screening, molecular docking, and molecular dynamic simulations targeting the exosite domains of ADAMTS-5 (the Disintegrin-like and spacer domain). The objective was to identify plant-derived flavonoids with favorable drug-like properties and specific interactions towards the ADAMTS-5 exosite as a more targeted alternative to catalytic-site inhibition. In this study, 847 flavonoids were screened using drug-likeness and ADME criteria to identify promising leads. The top 16 selected flavonoids were further subjected to molecular docking and SAR analysis. Of these compounds, Homoeriodictyol satisfied key drug-likeness criteria and exhibited the highest binding affinity to the Disintegrin-like domain, with a binding energy of −23.1 kcal/mol and favorable interactions. Molecular dynamics simulations of the Homoeriodictyol–ADAMTS-5 complex over 100 ns demonstrated stable binding throughout the trajectory. DCCM analysis and PCA further supported the proposed exosite-mediated modulation. To extend exosite mapping beyond the Disintegrin-like domain, this study also examined the spacer domain using a machine-learning-predicted structural model and identified key residues that contribute to ligand binding. Full article

A rapid targeted screening method for 22 compounds, including flavonoids, glycosides, and phenolics, in Dendrobium officinale was developed using UHPLC–MS/MS, demonstrating good linear correlation coefficients, precision, repeatability, and stability. D. officinale from the Guangnan and Maguan regions can be effectively classified into two distinct categories using PCA. In addition, OPLS-DA discriminant analysis enables clear separation between groups, with samples forming well-defined clusters. The 22 chemical components provide valuable origin-related information for D. officinale. The compounds with VIP values of >1 included eriodictyol, vanillic acid, protocatechuic acid, gentisic acid, and naringenin. The difference in naringenin content between D. officinale from the two production areas was minimal. By contrast, eriodictyol and vanillic acid were relatively abundant in D. officinale from Guangnan, while gentisic acid and protocatechuic acid were more prevalent in D. officinale from Maguan. The pathways with higher Kyoto Encyclopedia of Genes and Genomes enrichment were primarily associated with lipid metabolism and atherosclerosis, fluid shear stress and atherosclerosis, and nonalcoholic fatty liver disease. These findings suggest that D. officinale exhibits promising lipid-balancing properties and potential cardiovascular health benefits. Seven machine learning algorithms—Random Forest, XGBoost, Support Vector Machine, k-Nearest Neighbor, Backpropagation Neural Network, Random Tree, and CatBoost—demonstrated superior accuracy and precision in distinguishing D. officinale from the Guangnan and Maguan regions. The key compounds with higher weights—vanillic acid, chrysoeriol, trigonelline, isoquercitrin, gallic acid, 4-hydroxybenzaldehyde, eriodictyol, sweroside, apigenin, and homoeriodictyol—play a crucial role in model construction and the identification of D. officinale from the Guangnan and Maguan regions. The quantification of 22 compounds using UHPLC–MS/MS, combined with PCA, OPLS-DA, and machine learning, enables effective discrimination of D. officinale from these two Yunnan production areas. Full article

Acacia melanoxylon is highly valued for its commercial applications, with the heartwood exhibiting a range of colors from dark to light among its various clones. The underlying mechanisms contributing to this color variation, however, have not been fully elucidated. In an effort to understand the factors that influence the development of dark heartwood, a comparative analysis was conducted on the microstructure, substance composition, differential gene expression, and metabolite profiles in the sapwood (SW), transition zone (TZ), and heartwood (HW) of two distinct clones, SR14 and SR25. A microscopic examination revealed that heartwood color variations are associated with an increased substance content within the ray parenchyma cells. A substance analysis indicated that the levels of starches, sugars, and lignin were more abundant in SP compared to HW, while the concentrations of phenols, flavonoids, and terpenoids were found to be higher in HW than in SP. Notably, the dark heartwood of the SR25 clone exhibited greater quantities of phenols and flavonoids compared to the SR14 clone, suggesting that these compounds are pivotal to the color distinction of the heartwood. An integrated analysis of transcriptome and metabolomics data uncovered a significant accumulation of sinapyl alcohol, sinapoyl aldehyde, hesperetin, 2′, 3, 4, 4′, 6′-peptahydroxychalcone 4′-O-glucoside, homoeriodictyol, and (2S)-liquiritigenin in the heartwood of SR25, which correlates with the up-regulated expression of CCRs (evm.TU.Chr3.1751, evm.TU.Chr4.654_667, evm.TU.Chr4.675, evm.TU.Chr4.699, and evm.TU.Chr4.704), COMTs (evm.TU.Chr13.3082, evm.TU.Chr13.3086, and evm.TU.Chr7.1411), CADs (evm.TU.Chr10.2175, evm.TU.Chr1.3453, and evm.TU.Chr8.1600), and HCTs (evm.TU.Chr4.1122, evm.TU.Chr4.1123, evm.TU.Chr8.1758, and evm.TU.Chr9.2960) in the TZ of A. melanoxylon. Furthermore, a marked differential expression of transcription factors (TFs), including MYBs, AP2/ERFs, bHLHs, bZIPs, C2H2s, and WRKYs, were observed to be closely linked to the phenols and flavonoids metabolites, highlighting the potential role of multiple TFs in regulating the biosynthesis of these metabolites and, consequently, influencing the color variation in the heartwood. This study facilitates molecular breeding for the accumulation of metabolites influencing the heartwood color in A. melanoxylon, and offers new insights into the molecular mechanisms underlying heartwood formation in woody plants. Full article

Flavonoids exhibit various bioactivities including anti-oxidant, anti-tumor, anti-inflammatory, and anti-viral properties. Methylated flavonoids are particularly significant due to their enhanced oral bioavailability, improved intestinal absorption, and greater stability. The heterologous production of plant flavonoids in bacterial factories involves the need for enough biosynthetic precursors to allow for high production levels. These biosynthetic precursors are malonyl-CoA and l-tyrosine. In this work, to enhance flavonoid biosynthesis in Streptomyces albidoflavus, we conducted a transcriptomics study for the identification of candidate genes involved in l-tyrosine catabolism. The hypothesis was that the bacterial metabolic machinery would detect an excess of this amino acid if supplemented with the conventional culture medium and would activate the genes involved in its catabolism towards energy production. Then, by inactivating those overexpressed genes (under an excess of l-tyrosine), it would be possible to increase the intracellular pools of this precursor amino acid and eventually the final flavonoid titers in this bacterial factory. The RNAseq data analysis in the S. albidoflavus wild-type strain highlighted the hppD gene encoding 4-hydroxyphenylpyruvate dioxygenase as a promising target for knock-out, exhibiting a 23.2-fold change (FC) in expression upon l-tyrosine supplementation in comparison to control cultivation conditions. The subsequent knock-out of the hppD gene in S. albidoflavus resulted in a 1.66-fold increase in the naringenin titer, indicating enhanced flavonoid biosynthesis. Leveraging the improved strain of S. albidoflavus, we successfully synthesized the methylated flavanones hesperetin, homoeriodictyol, and homohesperetin, achieving titers of 2.52 mg/L, 1.34 mg/L, and 0.43 mg/L, respectively. In addition, the dimethoxy flavanone homohesperetin was produced as a byproduct of the endogenous metabolism of S. albidoflavus. To our knowledge, this is the first time that hppD deletion was utilized as a strategy to augment the biosynthesis of flavonoids. Furthermore, this is the first report where hesperetin and homoeriodictyol have been synthesized from l-tyrosine as a precursor. Therefore, transcriptomics is, in this case, a successful approach for the identification of catabolism reactions affecting key precursors during flavonoid biosynthesis, allowing the generation of enhanced production strains. Full article

Cucumber is an important vegetable crop, and grafts often affect the quality and wax loss in cucumber fruit and affect its value. However, their metabolites and molecular mechanisms of action remain unclear. Metabolome and transcriptome analyses were conducted on the fruit peels of self-rooted plants (SR) grafted with white seed pumpkin (WG). The results showed that there were 352 differential metabolites in the fruit peels of the SR and WG. The transcriptome analysis showed 1371 differentially expressed genes (DEGs) between the WG and SR. These differentially expressed genes were significantly enriched in plant hormone signal transduction, cutin, suberin, wax biosynthesis, phenylpropanoid biosynthesis, and zeatin biosynthesis. By analyzing the correlation between differential metabolites and differentially expressed genes, six candidate genes related to the synthesis of glycitein, kaempferol, and homoeriodictyol were identified as being potentially important. Key transcription factors belonging to the TCP and WRKY families may be the main drivers of transcriptional changes in the peel between the SR and WG. The results of this study have provided a basis for the biosynthesis and regulation of wax loss and quality in grafted cucumbers and represents an important step toward identifying the molecular mechanisms of grafting onto cucumber fruit. Full article

(1) Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is now widely accepted that neuroinflammation plays a key role in its pathogenesis. Eriodictyol (Eri) and homoeriodictyol (Hom), dihydroflavonoids extracted from a variety of plants, have been confirmed to display a relationship with neuroprotection. (2) Methods: An AD mouse model was constructed by intracerebroventricular (ICV) injection of the Aβ_25–35 peptide, and Eri and Hom were administered orally for 4 weeks. UPLC-MS/MS was used to determine whether Eri and Hom cross the blood–brain barrier to exert their therapeutic effects. Histological changes in the brain and levels of Aβ were evaluated, and Y-maze and new object recognition experiments were conducted to assess the effects of Eri and Hom on Aβ_25–35-induced memory impairment in mice. The levels of oxidative stress and apoptosis in peripheral immune cells and progenitor cells in the hippocampal region were analyzed by flow cytometry and in vitro assays. Western blotting and enzyme-linked immunosorbent assays (ELISA) were used to measure the expression levels of NLRP3 inflammasome-related proteins and inflammatory factors in the brain. The effect of nigericin (an agonist of the NLRP3 inflammasome) on Eri and Hom intervention in LPS-induced N9 microglia was examined using a High Content Screening System. (3) Results: Eri and Hom reduced neuronal damage in mouse brain tissue, decreased Aβ levels in the brain, downregulated oxidative stress and apoptosis levels, and improved learning and memory capacity by crossing the blood–brain barrier to exert its effects. Moreover, Eri and Hom inhibited NLRP3 inflammasome activation and ameliorated immune cell disorder. Furthermore, the effect of Eri and Hom on LPS-induced N9 microglia disappeared after the addition of nigericin to agonize NLRP3 receptors. (4) Conclusions: Eri and Hom improved Aβ_25–35-induced memory impairment in mice by inhibiting the NLRP3 inflammasome. Full article

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3′-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2′,5′-tetrahydroxy-4′-methoxyflavone (3), and five known compounds, namely homoeriodictyol (4), isocycloartobilo-xanthone (5), artocarpanone (6), naringenin (7), and artocarpin (8). From the screening result, A. chama extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC₅₀ of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds 3, 4, 5, 6, and 8 showed strong activity against Staphylococcus epidermidis, S. aureus, methicillin-resistant S. aureus, and Cutibacterium acnes. This study is the first report on phytochemical investigation with new compounds and biological activities of A. chama. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms. Full article

Yellow peel will adversely affect the appearance quality of cucumber fruit, but the metabolites and the molecular mechanism of pigment accumulation in cucumber peel remain unclear. Flavonoid metabolome and transcriptome analyses were carried out on the young peel and old peel of the color mutant L19 and the near-isogenic line L14. The results showed that there were 165 differential flavonoid metabolites in the old peel between L14 and L19. The total content of representative flavonoid metabolites in the old peel of L14 was 95 times that of L19, and 35 times that of young peel of L14, respectively. This might explain the difference of pigment accumulation in yellow peel. Furthermore, transcriptome analysis showed that there were 3396 and 1115 differentially expressed genes in the yellow color difference group (Young L14 vs. Old L14 and Old L14 vs. Old L19), respectively. These differentially expressed genes were significantly enriched in the MAPK signaling pathway–plant, plant–pathogen interaction, flavonoid biosynthesis and cutin, suberine and wax biosynthesis pathways. By analyzing the correlation between differential metabolites and differentially expressed genes, six candidate genes related to the synthesis of glycitein, kaempferol and homoeriodictyol are potentially important. In addition, four key transcription factors that belong to R2R3-MYB, bHLH51 and WRKY23 might be the major drivers of transcriptional changes in the peel between L14 and L19. Then, the expression patterns of these important genes were confirmed by qRT-PCR. These results suggested that the biosynthesis pathway of homoeriodictyol was a novel way to affect the yellowing of cucumber peel. Together, the results of this study provide a research basis for the biosynthesis and regulation of flavonoids in cucumber peel and form a significant step towards identifying the molecular mechanism of cucumber peel yellowing. Full article

The intake of sugar-sweetened beverages has been associated with an augmented prevalence of metabolic diseases, namely, obesity, type II diabetes, and metabolic syndrome. On the other hand, nowadays, it is broadly accepted that foods and beverages rich in (poly)phenols could contribute to reducing the incidence of these pathologies. In this sense, the objective of the work was to revalue second quality citrus fruits for the development of new beverages, rich in anthocyanins and flavanones (maqui berry and second qualities citrus-based), and evaluate the influence of alternative sweeteners (sucralose, sucrose, or stevia), regarding the bioaccessibility and bioavailability of these bioactive compounds in the frame of a chronic (longitudinal) intervention. To fulfill this objective, a longitudinal study of the urinary excretion of anthocyanins and flavanones, after 2-months of ingestion of the developed maqui-citrus beverage, by 138 volunteers (n = 46 per beverage) and the analysis of the resulting phenolic metabolites by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-ESI-QqQ-MS/MS) was carried out. As major results, the bioavailable metabolites of caffeic acid (CA), catechol (CAT), 3,4-di-hydroxyphenylacetic acid (DHPAA), eriodictyol (E), homoeriodictyol (HE), hippuric acid (HA), naringenin (N), trans-ferulic acid (TFA), 2,4,6-tri-hydroxybenzaldehyde (THBA), trans-isoferulic acid (TIFA), and vanillic acid (VA) were detected. Accordingly, significantly different bioavailability was dependent on the sweetener used, allowing proposing stevia and, to a lower extent, sucralose, as valuable alternatives to sucrose. Full article

Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging. Chronic exposure of the skin to UV radiation causes the induction of matrix metalloproteinases (MMPs), such as MMP-1, and consequently results in alterations of the extracellular matrix (ECM) and skin photoaging. Flavonoids are considered as potent anti-photoaging agents due to their UV-absorbing and antioxidant properties and inhibitory activity against UV-mediated MMP induction. To identify anti-photoaging agents, in the present study we examined the preventative effect of methoxyflavonoids, such as sakuranetin, isosakuranetin, homoeriodictyol, genkwanin, chrysoeriol and syringetin, on UV-B-induced skin photo-damage. Of the examined methoxyflavonoids, pretreatment with isosakuranetin strongly suppressed the UV-B-mediated induction of MMP-1 in human keratinocytes in a concentration-dependent manner. Isosakuranetin inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling components, ERK1/2, JNK1/2 and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of isosakuranetin on UV-induced MMP-1 production in human keratinocytes. Isosakuranetin also prevented UV-B-induced degradation of type-1 collagen in human dermal fibroblast cells. Taken together, our findings suggest that isosakuranetin has the potential for development as a protective agent for skin photoaging through the inhibition of UV-induced MMP-1 production and collagen degradation. Full article