Search Results (63)

Methoxyflavones, along with chalcones and phenolic acids, belong to natural polyphenols. Apart from their antioxidant function, in plants, they act as pigments and are a part of plant chemical defense system. A member of this group is pedalitin, which expresses a range of interesting biological properties. The compound acts as an anticancer agent, strengthens the immune system, improves insulin sensitivity, protects internal organs, and also shows anti-inflammatory and neuroprotective activity. Due to the constant need for alternative therapies for treatment and prevention of lifestyle diseases, O-methylated flavonoids, including pedalitin, may serve as natural lead molecules in designing new structures with significant pharmacological potential. This review summarizes the literature reports on obtaining pedalitin and assessing its biological activity, also in the context of further functionalization of this compound and potential new applications. Full article

Salvia sclarea L. extract contains various bioactive components such as flavonoids and fatty acids, exhibiting anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the effects of Salvia sclarea L. extract on the gut microbiota and serum metabolome in lambs. Sixty 2-month-old Chinese Merino female lambs (body weight 20 ± 2 kg) were randomly assigned to five groups. The control (CK) group received the basal diet only, while the treatment groups received the basal diet supplemented with 0.04 mL/kg (CL1), 0.08 mL/kg (CL2), 0.12 mL/kg (CL3), and 0.16 mL/kg (CL4) of Salvia sclarea L. extract, respectively. The results showed that Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria were identified as the dominant phyla across all groups (>90%). Compared with the CK group, CL1 and CL2 groups significantly reduced the relative abundance of Tenericutes (decreased by 38.2% and 32.9%, respectively, p < 0.05); the relative abundance of Patescibacteria in the CL1 group was significantly lower (decreased by 55.2%, p < 0.05). At the genus level, Ruminococcaceae constituted a substantial proportion, including Ruminococcaceae UCG-005, UCG-010, UCG-014, and NK4A214 group. STAMP analysis revealed that Klebsiella was significantly enriched in CL2, CL3, and CL4 groups compared to the CK group (p < 0.05). Correlation analysis between microbiota and immune indices showed that Christensenellaceae R-7 group was significantly negatively correlated with TNF-α (p < 0.05); Ruminococcaceae UCG-005 was significantly negatively correlated with IFN-γ (p < 0.05) and showed a negative correlation trend with immunoglobulins (IgA, IgG, IgM). Conversely, Ruminococcaceae UCG-014 was significantly positively correlated with IL-4 (p < 0.05) but showed a negative correlation trend with IgM. Untargeted metabolomics analysis identified 8, 18, 25, and 20 differential metabolites in CL1, CL2, CL3, and CL4 groups, respectively. Notably, 3-hydroxy-7-methoxyflavone and Gamma-Glu-Cys were significantly upregulated across all treatment groups. KEGG pathway enrichment analysis indicated that these differential metabolites were primarily involved in nucleotide metabolism, fatty acid biosynthesis, and oxidative stress-related pathways. Further Spearman correlation analysis revealed significant associations between gut microbiota and differential metabolites. Specifically, g_Klebsiella was significantly positively correlated with 3-Hydroxycapric acid and 3-hydroxy-7-methoxyflavone (p < 0.05). In conclusion, Salvia sclarea L. extract modulates host energy metabolism by regulating nucleotide metabolism and fatty acid biosynthesis, and enhances immune function by alleviating oxidative stress, through the remodeling of gut microbiota and serum metabolome. Full article

Background/Objectives: Sexual dysfunction is a prevalent and multifactorial condition affecting a large proportion of the global population, with limited therapeutic options beyond pharmacological approaches primarily targeting erectile dysfunction. This has increased interest in botanical supplements for sexual health, although mechanistic evidence and clear links between phytochemical composition and biological activity remain scarce. The present study provides an integrative evaluation of a commercial Turnera diffusa extract (Liboost^®) formulated to support sexual health by combining detailed phytochemical characterization with targeted in vitro mechanistic assays. Methods: The extract was characterized by HPLC-DAD-HRMS, enabling the identification and semi-quantification of its major constituents. A total of 49 compounds were detected, predominantly flavonoids, including luteolin- and apigenin-derived glycosides, flavonols, methoxyflavones, flavanones, and coumaroyl derivatives, with a total quantified flavonoid content of 15.9 mg·g⁻¹. Biological activity was evaluated in human cell models without cytotoxic effects at the tested concentrations. Results: Liboost^® significantly reduced PDE5 expression, inhibited aromatase activity, and moderately increased nitric oxide production. These complementary effects suggest a multi-target modulation of pathways involved in sexual function, integrating vascular, endocrine, and nitrergic mechanisms. Conclusions: Although limited to in vitro models, the findings provide mechanistic support for the biological activity of T. diffusa extracts and highlight the importance of linking phytochemical composition with functional evidence when evaluating botanical supplements. Full article

Primula vulgaris Huds., one of the 33 Primula L. species native to Europe, occurs across diverse habitats, including the biodiversity hotspot of the Prespa Lake region (NW Greece). Building on previous phytochemical studies, the present work provides the first detailed characterization of flavonoids from the aerial parts of the species growing wild in the area. Using classical chromatographic separation methods combined with spectrometric techniques, seven metabolites were isolated and structurally elucidated from the dichloromethane and methanol extracts. These included flavone (1), 2′-methoxyflavone (2), 3′-methoxyflavone (3), 3′-hydroxy-4′,5′-dimethoxyflavone (4), kaempferol-3-O-β-glucopyranosyl-(1→2)-β-glucopyranosyl-(1→6)-β-glucopyranoside (6), 3′-hydroxyflavone-4′-O-β-glucopyranoside (7) and 5,6,2′,3′,6′-pentamethoxyflavone (5), which was reported for the first time in this species. Additionally, the total phenolic content (TPC) of the methanol extract was determined using the Folin–Ciocalteu method, demonstrating 46.46 ± 2.48 mg GAE/g extract, while through the DPPH radical scavenging assay, it expressed moderate activity. Overall, these results provide novel insights into the flavonoid composition of Greek P. vulgaris and support its potential for further pharmacological investigations and herbal applications. Full article

Reactive oxygen species (ROS) generated by ultraviolet (UV) radiation accelerate skin aging by activating matrix metalloproteinase-1 (MMP-1) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, antioxidants that can suppress ROS generation and downstream signaling cascades are considered promising anti-aging agents. In this study, five methoxyflavones were isolated from Kaempferia parviflora (black ginger) rhizomes—5,7,3′,4′-tetramethoxyflavone (1), 3,5,7,4′-tetramethoxyflavone (2), 5,7,4′-trimethoxyflavone (3), 3,5,7,3′,4′-pentamethoxyflavone (4), and 5,7-dimethoxyflavone (5)—using LC–MS-guided fractionation and identified via NMR and LC–MS analysis. Their biological activities were evaluated in tumor necrosis factor-α (TNF-α)-stimulated normal human dermal fibroblasts (NHDFs). All methoxyflavones, except compound 3, significantly suppressed TNF-α-induced ROS generation, while compounds 3–5 markedly reduced MMP-1 secretion. Among them, compounds 4 and 5 exerted the strongest protective effects by modulating distinct MAPK pathways: compound 4 selectively inhibited p38 phosphorylation, whereas compound 5 selectively suppressed ERK phosphorylation. Both compounds attenuated ECM degradation and enhanced antioxidant defenses in a concentration-dependent manner. Collectively, these findings highlight the mechanistic significance of methoxyflavones 4 and 5 as dual-acting antioxidant and ECM-protective agents that counteract skin aging through selective regulation of MAPK signaling. Their potential as natural anti-photoaging ingredients warrants further validation in in vivo models and clinical studies for future skincare applications. Full article

Background: Xerophilous scrubland is a semi-desert ecosystem characterized by a wide diversity of shrubs, which have secondary compounds with nutraceutical potential that could be used as feed for livestock, specifically by goats, since this species has developed behavioral and physiological adaptations that allow it to take advantage of the plant resources of said scrubland. Objective: To evaluate the nutraceutical potential of Havardia pallens and Vachellia rigidula, native species of the xerophilous scrubland, when incorporated as ingredients in goat diets. Methods: Integral diets for male goats were prepared, formulated with 35% inclusion of Havardia pallens, Vachellia rigidula, and Medicago sativa, the latter used as a plant control species. The content of flavonoids and total phenols was compared using colorimetric methods, and the antioxidant capacity was measured using the FRAP method. RP-HPLC-ESI-MS characterized the bioactive compounds in the different extracts. Statistical analysis was performed by ANOVA. Results: The aqueous extraction of Vachellia rigidula showed the highest concentration of total phenols ($\overline{\mathrm{x}}$ = 18.22 mg GAE/g⁻¹), followed by the ethanolic extract in the same species ($\overline{\mathrm{x}}$ = 17.045 mg GAE/g⁻¹). Similarly, Vachellia rigidula presented the highest antioxidant capacity ($\overline{\mathrm{x}}$ = 144,711.53 µmol TE/g⁻¹), while Medicago sativa presented the lowest ($\overline{\mathrm{x}}$ = 11,701.92 µmol TE/g). The RP-HPLC-ESI-MS analysis revealed that Vachellia rigidula presented a higher abundance of flavones, catechins, flavonols, methoxyflavones, and tyrosols. However, Harvardia pallens presented higher levels of methoxycinnamic and hydroxycinnamic acids. One-way ANOVA results showed that diets containing 35% Vachellia rigidula and Havardia pallens significantly contrasted (p < 0.05), increased the content of secondary compounds and antioxidant capacity compared to the control species. Furthermore, including Vachellia rigidula led to a significantly higher antioxidant capacity (p < 0.05) than diets with Havardia pallens or Medicago sativa. Conclusions: Incorporating the leguminous shrubs Vachellia rigidula and Havardia pallens into the formulation of comprehensive diets for buck goats improves the content and availability of phenols, flavonoids, and antioxidants. However, in vivo evaluation of these diets is important to determine their physiological and productive effects on the animals. Full article

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and dysregulated chemokine signaling. Kaempferia parviflora (KP) has long been valued for its medicinal properties; however, its specific role in psoriasis treatment remains unclear. This study investigates the anti-psoriatic potential of methoxyflavones derived from KP through an integrated approach combining network pharmacology, molecular docking, and experimental validation. A total of 232 target genes were identified as being associated with KP bioactive compounds, of which 64 overlapped with psoriasis-related genes implicated in chemokine signaling pathways. Molecular docking analyses revealed that key methoxyflavones interact with pivotal proteins such as protein kinase B (AKT1 or AKT), proto-oncogene tyrosine-protein kinase (SRC), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), suggesting their potential involvement in modulating inflammation. Experimental results confirmed that 5,7,4′-trimethoxyflavone and 3,5,7-trimethoxyflavone significantly inhibited keratinocyte proliferation, migration, and macrophage activation, key processes in psoriasis progression. Additionally, both compounds reduced nitric oxide production, supporting their anti-inflammatory effects. Western blot analysis further demonstrated that these compounds tended to decrease the phosphorylation levels of AKT and SRC, supporting their role in influencing inflammatory signaling pathways. These findings suggest that methoxyflavones from KP act through multi-target mechanisms, offering potential as natural therapeutic agents for psoriasis. Further, in vivo studies are needed to validate their efficacy and explore their clinical applications. Full article

In this study, three new undescribed triterpene saponins named primulasaponin III–V (19–21) were isolated from the roots of Primula veris L. of Bulgarian origin together with the known primulasaponin I. Their structures were elucidated via 1D and 2D NMR spectroscopy and HR-ESI-MS. In addition, 17 known phenolic compounds (six flavones, three acetophenones, four bisbibenzyls, and four phenolic glycosides) were identified in the chloroform and methanol extracts. Among them, flavone, 2′-methoxyflavone, 3′-methoxyflavone, 3′-hydroxy-4′,5′-dimethoxyflavone, 2′,5′-dimethoxyflavone, 3′-methoxy-4′,5′-methylendioxyflavone, paeonol, 2-primeverosyl-5-methoxy-acetophenone, and paeonolide were detected for the first time in the roots of P. veris. The minimum inhibitory and minimum bactericidal concentrations of the chloroform and methanol extracts of P. veris roots and the saponin-enriched fraction were determined, with MIC values ranging between 0.5 and 1 mg/mL. Additionally, the tested samples were evaluated for their ability to inhibit biofilm formation in the presence of sub-MICs. All tested samples showed better biofilm inhibition of Gram-negative strains compared to Gram-positive strains. The strongest effect was observed for the chloroform extract against the biofilm formation of Pseudomonas aeruginosa, while the saponin-enriched fraction showed the highest percentage of biofilm inhibition of Escherichia coli, Staphylococcus aureus, and Staphylococcus mutans. At the same time, chloroform extract showed lower cytotoxicity against human keranocyte cell line HaCaT, as compared with methanol extract and the saponin-enriched fraction. Full article

The value-added effect of white rot fungi on the feed of Astragalus membranaceus var. mongholicus (AMM) stems was explored. All four types of white rot fungi (Lentinus sajor-caju, Pleurotus ostreatus, Lentinula edodes, and Phanerodontia chrysosporium) reduced the lignocellulose content in AMM stems, improved in vitro dry matter digestibility (IVDMD), and influenced the activity of lignocellulose-degrading enzymes. Lentinus sajor-caju and Phanerodontia chrysosporium exhibited superior effects on lignin degradation and IVDMD and significantly altered non-volatile metabolites and antioxidant capacity. Lentinus sajor-caju fermentation resulted in the strongest antioxidant activity compared to that in the other fungal treatments. The fold change (FC) ratio (>100) of sakuranetin, 2′,6′-Di-O-acetylononin, isoformononetin, and artocarpin was compared between Lentinus sajor-caju and Phanerodontia chrysosporium. Among the phenolic compounds, flavonoids play a key role in antioxidant activity, with 5,6-Dihydroxy-7-methoxyflavone showing a strong correlation with antioxidant activity. This study provides valuable insights for utilizing AMM stem waste in the context of traditional Chinese medicine. Full article

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a pulmonary disease with high mortality associated with inflammation. During the development of ALI/ARDS, macrophages usually polarize toward M1 pro-inflammatory macrophages, promoting the inflammatory response in ALI/ARDS and aggravating lung tissue damage. Natural compounds with anti-inflammatory activity have achieved excellent results in the treatment of ALI/ARDS through different regulatory modes, including macrophage polarization. Of note, flavonoid, brevilin A, and tetrahydropalmatine play an important role in the treatment of ALI/ARDS by modulating the phenotypic polarization of macrophages and their pro-inflammatory cytokine expression in innate immune cells of the lung. Flavonoids are a kind of naturally occurring polyphenol compound, which has antioxidant and anti-inflammatory activities. Studies have found that some flavonoids can alleviate ALI/ARDS through inhibiting the expression of inflammatory cytokines in macrophages. Among them, 5-methoxyflavone, acacetin, grape seed proanthocyanidins, and luteolin can also regulate macrophage polarization. Therefore, the in-depth exploration of the regulatory mechanism of macrophages can lay the foundation for the application of flavonoids in alleviating inflammation-related lung injury. This review focuses on the macrophage polarization effects of different natural compounds and their potential anti-inflammatory mechanisms in the treatment of ALI/ARDS. Full article

2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitating ligand–protein binding mechanisms and activating cascading downstream signaling pathways leading to cell death. However, the lipophilic nature of these analogs is a key concern as it impacts drug membrane transfer. While lipophilicity is crucial for drug efficacy, the excessive lipophilic effects in flavonoids can reduce water solubility and hinder drug transport to target sites. Recent in vitro studies suggest that the incorporation of polar hydroxyl groups which can form hydrogen bonds and stabilize free radicals may help overcome the challenges associated with methoxy groups while maintaining their essential lipophilic properties. Naturally coexisting with methoxyflavones, this review explores the synergistic role of hydroxy and methoxy moieties through hydrogen bonding capacity in maximizing cytotoxicity against cancer cell lines. The physicochemical analysis revealed the potential intramolecular interaction and favorable electron delocalization region between both moieties to improve cytotoxicity levels. Together, the analysis provides a useful strategy for the structure–activity relationship (SAR) of flavonoid analogs in distinct protein markers, suggesting optimal functional group positioning to achieve balanced lipophilicity, effective hydrogen bonding, and simultaneously minimized steric hindrance in targeting specific cancer cell types. Full article

The aim of this study is to isolate and identify the secondary metabolites of the aerial part of the plant Centaurea bruguieriana (DC.) Hand. -Mazz. subsp. belangeriana (DC.) Bornm. (Centaurea phyllocephala) (Asteraceae), and to study the biological activities of the extracts and isolated compounds with in vitro tests. With the use of chromatography and spectroscopy we identified three elemanolides: 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy) dehydromelitensine (1), 8α-O-(3-hydroxy-4-acetoxy-2-methylene-butanoyloxy) dehydromelitensine (2) and methyl 6α,8α,15-trihydroxyelema-1,3,11(13)-trien-12-oate (3); two germacranolides: cnicin (4) and 4′-O-acetylcnicin (5); one eudesmanolide: malacitanolide (6); five flavonoids: cirsilineol (7), eupatorine (8), 5-hydroxy, 6,7,3′,4′-tetramethoxy-flavone (9), 3,4′,5,7-tetrahydroxy-6-methoxyflavone 3-O-β-D-glucopyranoside (10) and astragalin (11); and also p-OH-benzoic acid (12) and 3-hydroxy-2-methyl-butyrolactone (13). All the isolated compounds were evaluated in silico with the use of molinspiration, while the crude extract, the organic phase B and compounds 2, 4, 5 and 6 were tested as antioxidants and anti-inflammatories for the inhibition of lipid hyperoxide and the inhibition of lipoxygenase. Full article

Liver disease is a global public problem, and the cost of its therapy is a large financial burden to governments. It is well known that drug therapy plays a critical role in the treatment of liver disease. However, present drugs are far from meeting clinical needs. Lots of efforts have been made to find novel agents to treat liver disease in the past several decades. Acacetin is a dihydroxy and monomethoxy flavone, named 5,7-dihydroxy-4′-methoxyflavone, which can be found in diverse plants. It has been reported that acacetin exhibits multiple pharmacological activities, including anti-cancer, anti-inflammation, anti-virus, anti-obesity, and anti-oxidation. These studies indicate the therapeutic potential of acacetin in liver disease. This review discussed the comprehensive information on the pathogenesis of liver disease (cirrhosis, viral hepatitis, drug-induced liver injury, and hepatocellular carcinoma), then introduced the biological source, structural features, and pharmacological properties of acacetin, and the possible application in preventing liver disease along with the pharmacokinetic and toxicity of acacetin, and future research directions. We systemically summarized the latest research progress on the potential therapeutic effect of acacetin on liver disease and existing problems. Based on the present published information, the natural flavone acacetin is an anticipated candidate agent for the treatment of liver disease. Full article

Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity of pure phenolic compounds has not been reported yet. The chromatographic of a methanolic extract yielded twenty-two compounds, viz.: naringenin 4′-O-glucoside (1), 3′,4′,7-trihydroxyflavanone (butin) (2), liquiritin (3), liquiritin apioside (4), abyssinone (5), glabrol (6), isoliquiritin (7), neoisoliquiritin (8), isoliquiritin apioside (9), licuraside (10). 3’[O], 4’-(2,2-dimethylpyrano)-3,7-dihydroxyflavanone (11), glabrocoumarin (12), glabrene (13), isomedicarpin (14), 7-hydroxy-4′-methoxyflavone (formononetin) (15), ononin (16), glycyroside (17), (3S)-7,4′-dihydroxy-2′-methoxyisoflavan (18), glabridin (19), neoliquiritin (20), 3,11-dioxooleana-1,12-dien-29-oic acid (21), and 3-oxo-18β-glycyrrhetinic acid (22). The results of the neuroprotection evaluation showed that G. glabra total extract (TE) and compounds 1, 7, 11, 16, and 20 protected SH-SY5Y cells by inhibiting the depletion of ATP and elevated caspase 3/7 activities induced by MPP+. Indeed, this study reports for the first time the structure and activity of compound 11 and the neuroprotective activity of some phenolic constituents from G. glabra. Full article

In this study, based on ethnobotanical data recorded in Transylvania, the polyphenolic compounds and the permeability of the aerial part’s extract of Tanacetum balsamita were investigated. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was applied for the analysis of the extracts. Parallel artificial membrane permeability assay (PAMPA) for the gastrointestinal tract and the blood–brain barrier was conducted. In the ethanolic and aqueous extracts of the species traditionally used for wound, furuncle, and liver disorders, 92 polyphenols were characterized (e.g., flavonoid, hydroxycinnamic acid, catechin, dihydroxybenzoyl, lignan derivatives, and a monoterpene) including 54 compounds identified for the first time in the plant. In the PAMPA tests, eight components were shown to be capable of passive diffusion across the studied membranes. These include apigenin and seven methoxylated flavonoid derivatives. Based on these results, methoxylated flavonoids might promote the pharmacological potential of T. balsamita to be applied in the enhancement of novel remedies. Full article