Search Results (719)

The flower color of Rhododendron is primarily determined by anthocyanin biosynthesis, with cytochrome P450 CYP75 family members, particularly flavonoid 3′,5′-hydroxylase (F3′5′H), playing a central role. However, the composition and functional characterization of CYP75 genes in Rhododendron remain insufficiently explored. This study performed genome-wide identification of the CYP75 gene family using the Rhododendron simsii reference genome and functionally characterized the corresponding F3′5′H homolog cloned from Rhododendron × hybridum petals (red cultivar and pink cultivar). Seven RsCYP75 genes were identified, categorized into two subfamilies: RsCYP75A (A1–A5) and RsCYP75B (B1–B2), with a prominent cluster on chromosome 13. All encoded proteins contained a conserved cytochrome P450 domain and typical heme-binding motifs. Among these, RhCYP75A2 showed the highest expression level in red petals at full blooming period and was designated as RhF3′5′H. RhF3′5′H encodes a basic membrane protein with the characteristic F3′5′H motif, with its transcript most abundant in flowers. Transient overexpression of RhF3′5′H in red R. × hybridum petals resulted in a 9.74-fold increase in its transcript levels and a 1.25-fold increase in anthocyanin content compared to that in the control accompanied by the up-regulation of CHS, F3H, DFR and ANS. Conversely, RhF3′5′H silencing reduced anthocyanin accumulation but increased CHS and F3H transcript levels, suggesting a compensatory transcriptional response in the upstream anthocyanin pathway. Moreover, RhF3′5′H was heterologously expressed in E. coli Rosetta as an MBP fusion protein, purified, and identified by LC-MS/MS and ELISA. The protein showed the ability to promote anthocyanin accumulation. Molecular docking analysis demonstrated that RhF3′5′H can bind to naringenin and dihydrokaempferol. These results confirm that RhF3′5′H is a functional F3′5′H-type CYP75A enzyme and a positive regulator of anthocyanin accumulation in Rhododendron petals. This work enriches the CYP75 gene catalog in Rhododendron and provides candidate genes for future studies on flower color regulation and molecular breeding. Full article

Botanical extracts represent a rich and sustainable source of polyphenolic compounds with significant potential in anticancer research. Among these, hesperidin, naringenin, hydroxytyrosol, oleuropein, and quercetin have attracted considerable attention due to their abundance in widely consumed plants such as citrus fruits, olive derivatives, and various fruits and vegetables. However, their clinical translation is hindered by intrinsic limitations including poor solubility, low stability, and limited bioavailability. In this context, nanotechnology-based drug delivery systems have emerged as a promising strategy to enhance the therapeutic performance of these bioactive compounds. This review provides an overview of polyphenol-rich botanical matrices and focuses on recent advances in their nanoformulation. Various nanocarriers, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, and nanoemulsions, are discussed in terms of their ability to improve physicochemical properties, protect against degradation, and enhance delivery efficiency. Special attention is given to the challenges associated with the encapsulation of complex botanical extracts and the need to preserve their compositional integrity and synergistic effects. Overall, nanoformulation represents a powerful approach to overcome current limitations and unlock the full potential of plant-derived polyphenols in anticancer applications. Full article

The increasing global burden of cancer, together with the need for more sustainable resource management, has stimulated growing interest in the valorization of agro-industrial plant residues as sources of bioactive compounds with therapeutic potential. This review highlights the potential of plant by-products—including citrus peels, olive leaves, date palm residues, and tea and coffee processing wastes—as sustainable reservoirs of polyphenols and other phytochemicals with significant anticancer activity. Key compounds such as hesperidin and naringenin from citrus peels, oleuropein and hydroxytyrosol from olive leaves, quercetin and syringic acid from date palm residues, and chlorogenic acid and epigallocatechin gallate from tea and coffee by-products have demonstrated promising antitumor effects in both in vitro and in vivo studies. These molecules exert their activity through multiple mechanisms, including the inhibition of cancer cell proliferation, induction of apoptosis, regulation of the cell cycle, and modulation of major oncogenic signaling pathways such as PI3K/AKT, MAPK, NF-κB, and EGFR. For instance, hydroxytyrosol induces apoptosis and cell cycle arrest while inhibiting the PI3K/AKT and MAPK pathways. Quercetin limits metastasis and glycolysis and suppresses VEGF, PKM2, and AKT signaling. Ferulic acid suppresses tumor growth by inhibiting the PI3K/AKT and JAK2/STAT6 pathways, thereby promoting apoptosis (in vitro and in vivo). In addition to their pharmacological potential, the recovery of these compounds from plant waste supports circular economy strategies by reducing environmental impact and promoting the development of value-added products. Future research should focus on optimizing extraction methods, improving bioavailability and stability, and validating safety and efficacy through well-designed preclinical and clinical studies. Full article

Dihydroflavonol 4-reductase (DFR) plays a pivotal role in regulating flavonoid and anthocyanin biosynthesis, governing the accumulation of plant secondary metabolites. This study aimed to characterize the DFR gene family in Ginkgo biloba and elucidate the function of the predominant gene GbDFR2 in the flavonoid metabolic network. Through transcriptome analysis, three differentially expressed GbDFR genes were identified. Bioinformatic analysis revealed that all three GbDFR proteins are hydrophilic and acidic and belong to the NADB_Rossmann superfamily. RT-qPCR analysis of different tissues of ginkgo revealed that all three GbDFR genes exhibited the highest expression levels in the leaves. An overexpression vector of GbDFR2 was constructed and stably transformed into Nicotiana benthamiana. Metabolomic and qPCR analyses showed that heterologous GbDFR2 expression significantly remodeled the flavonoid profile, upregulating sakuranetin and 3,7-Di-O-methylquercetin while downregulating narcissin and naringenin chalcone. Additionally, it upregulated endogenous NbCHI and NbDFR, and suppressed the transcription factors NbMYL2b and NbERF4a. These findings suggest that GbDFR2 can act as a regulator of flavonol biosynthesis and provide a candidate gene for the metabolic engineering of flavonoids in woody plants. Full article

Background/Objectives: Natural compounds occupy a pharmacologically rich chemical space, characterized by abundant scaffolds, extensive functional group elaboration, and defined stereochemistry. In this context, Helichrysum italicum, a Mediterranean medicinal plant, represents a valuable source of polyphenols with multiple biological and pharmacological activities. Methods: Here, we introduce an inverse molecular docking fingerprint approach to systematically investigate eight major Helichrysum italicum polyphenols, including $\alpha$-pyrones (arzanol, ethylpyrone), flavonols (gnaphaliin, kaempferol, quercetin), and flavanones (naringenin, pinocembrin, hesperetin). More than 40,000 human protein structures from the Protein Data Bank were screened to generate target-based inverse docking score fingerprints for each compound. Results: Hierarchical clustering of these fingerprints revealed shared binding patterns among structurally related polyphenols and enabled hypothesis generation regarding potential synergistic effects. Notably, favorable interactions were identified with PPARG and CARM1, supporting therapeutic relevance in inflammation and cancer, alongside additional targets associated with neurodegeneration and bone metabolism. Conclusions: This study establishes inverse docking fingerprints as a robust, mechanism-oriented method for natural product research and highlights Helichrysum italicum polyphenols as starting points for medicinal chemistry and drug discovery. Full article

Naringenin (NRG), a poorly water-soluble flavonoid with anticancer potential, suffers from limited bioavailability due to low aqueous solubility and poor membrane permeation. In this study, NRG nanocrystals (NRG-NCs) were developed using an optimized antisolvent precipitation–probe sonication method and incorporated into a 20% (w/w) Pluronic^® F127 hydrogel for enhanced delivery. The optimized NRG-NCs exhibited a mean particle size of ~195 ± 5 nm, polydispersity index of ~0.20 ± 0.02, and zeta potential of −24 ± 3 mV. Percentage yield and drug loading capacity were 88.6 ± 2.3% and 78.4 ± 1.8%, respectively. Nanocrystal formation resulted in ~9-fold enhancement in saturation solubility compared to raw NRG. The NRG-NCs gel demonstrated rapid dissolution (~90% release within 120 min) and ~2.5-fold higher ex vivo permeation across the Strat-M^® membrane relative to pure NRG. The hydrogel exhibited suitable physicochemical properties (viscosity ~12,850 cP; pH 6.2 ± 0.1; spreadability 5.8 ± 0.3 cm) and maintained >92% drug content after 30 days of refrigerated storage. Mechanistic studies revealed dose-dependent cytotoxicity, characterized by increased intracellular ROS, mitochondrial membrane depolarization, and elevated caspase-3 activity, confirming ROS-mediated apoptosis. In conclusion, the nanocrystal–hydrogel platform significantly enhances the solubility, permeation, and pro-apoptotic efficacy of NRG, demonstrating its potential for skin cancer treatment. Full article

The health benefits of jujubes are closely related to their active substances. In this study, the active substances in ‘huizao’ (HZ), ‘junzao’ (JZ), ‘hamidazao’ (HMDZ), ‘kashigerexiaozao’ (KSGEXZ) and ‘yuanlingzao’ (YLZ) jujube varieties were identified via ultrahigh-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). After identification, a total of 1583 metabolites were found in jujube fruits, covering 13 major categories including alkaloids, amino acids and their derivatives. Pairwise comparisons revealed 518–755 differentially abundant metabolites across cultivars, and each variety had its main dominant metabolites. Through network pharmacology, 141 potential disease-related bioactive compounds were screened out, and key compounds were identified through molecular docking. These substances bind to the key target TP53 through hydrogen bonding and hydrophobic interactions. Among them, catechin, naringenin, and coniferin had the strongest binding affinities. These data increase our understanding of the active components of jujube and provide valuable information for the sustainable cultivation of jujubes for health applications. Full article

Background/Objectives: Salvia chinensis Benth (SJC), as a traditional medicinal plant, has garnered significant attention for its extensive pharmacological activities. However, a systematic investigation of its comprehensive chemical profile and the underlying mechanisms in colorectal cancer (CRC) remains to be elucidated. This study aims to elucidate the active compounds and targets responsible for the anti-colorectal cancer effects of the aqueous extract of SJC. Methods: An integrated strategy was employed. The chemical profile of the SJC aqueous extract was analyzed by UPLC-MS/MS. Its anticancer activities, including effects on cell proliferation, migration, and apoptosis, were evaluated using the HCT-116 CRC cell line. An integrated transcriptomic and bioinformatic approach, followed by protein–protein interaction (PPI) network analysis, was used to identify key molecular pathways and targets. Finally, molecular docking and cellular assays were performed to screen for potential bioactive compounds. Results: A total of 60 natural compounds were tentatively identified in SJC. SJC inhibited the proliferation, migration, and invasion of HCT-116 colorectal cancer cells. Through combined transcriptomic and bioinformatic analysis, four candidate key genes were initially identified. Further PPI network analysis prioritized CXCL8 as a key candidate among the four candidate targets. Molecular docking against CXCL8, together with subsequent cellular experiments, validated naringenin as a potential bioactive constituent contributing to the anti-CRC activity of SJC. Conclusions: This study provides a comprehensive chemical profile of SJC and offers significant insights into its potential anticancer mechanisms in CRC by identifying candidate targets and a potential bioactive constituent. While these findings are preliminary and require further experimental validation through additional CRC cell lines and in vivo models, they establish a solid foundation for future research into the therapeutic applications of SJC for colorectal cancer. These planned studies will help to further elucidate the underlying mechanisms and assess the translational potential of SJC. Full article

Plasmid copy number (PCN) is a key factor limiting the expression level of heterologous proteins in yeast. Static strategies for enhancing PCN, such as reducing the transcriptional intensity of selection markers or increasing selection pressure, only maintain PCN at a single fixed level and struggle to achieve dynamic, precise, and reversible copy number regulation. This study established a dynamic plasmid copy number regulation strategy based on CRISPR interference (CRISPRi). Flexible control of PCN was achieved by designing specific guide RNAs (gRNAs) and integrating them into the inducible CRISPRi system. Optimization of the gRNA target site, inducer concentration, and induction timing resulted in a >2-fold increase in the fluorescence intensity of yeast-enhanced green fluorescent protein (yeGFP) compared with the group without induction. Using naringenin synthesis as proof-of-concept, this regulatory tool was applied to modulate the expression of chalcone synthase (CHS), the rate-limiting enzyme in naringenin biosynthesis. Finally, the yield of naringenin increased by 35.62% under the optimal induction conditions. Full article

The chemical composition of Iris songarica rhizome extracts was systematically investigated using GC-MS and UHPLC-MS. Their biological activity was further evaluated in vivo. The chloroform rhizome extract contained 33 identified compounds distributed across five main classes. Flavonoids predominated (50.7% of total ionic current), with tectochrysine (42.15%) as the major component, followed by 3,7-dihydroxy-2-(3,4-dimethoxyphenyl)-4H-chromene-4-one (5.18%) and a naringenin derivative (3.99%). Fatty acid esters comprised 30.6%, dominated by linoleic acid ethyl ester (11.05%), ethyl oleate, and hexadecanoic acid ethyl ester. Phenolic and aromatic compounds accounted for 14.24%, including (E)-4-(3-hydroxyprop-1-en-1-yl)-2-methoxyphenol and flamenol. Quantitative HPLC revealed hesperetin (69.72 µg/mL) and fisetin (12.32 µg/mL) as predominant in the 50% aqueous ethanol extract, and cinarin (6.28 µg/mL) in the ethyl acetate root extract. HPLC-MS identified 25 polyphenols, mainly isoflavonoids and flavones, with key markers songaricol, irilin B, tectorigenin, irisflavone A, and irizon B, some reported for the first time in Kazakhstan irises. Biological evaluation demonstrated potent activity: the 50% aqueous ethanol extract inhibited xylene-induced ear oedema in mice by 72.7% at 300 mg/kg, comparable to diclofenac (90.9%), without observable toxicity. These findings confirm I. songarica as a valuable source of bioactive polyphenols with anti-inflammatory potential. Full article

Cancer ranks as one of the top causes of death worldwide, and the World Health Organisation (WHO) estimates an increase of up to 55% in cases over the next 15 years, reaching 300 million cases worldwide. Current approaches to the treatment of cancer, such as chemotherapy and radiation therapy, have been used with continuous significant advancements. However, these conventional methods have harmful side effects that can last a lifetime. Today, there is growing interest in developing alternative cancer therapies from natural products or complementary medicine. One of the natural sources that has shown promise as an anticancer agent is honey, which has long been applied as a complementary medicine, and its beneficial health effects on various diseases in both animal and human models have been widely studied. Malaysian honey, such as Tualang, pineapple, Gelam, Kelulut, and Acacia, possesses a rich composition of phytochemicals, including polyphenols and flavonoids, which are reported to have promising anticancer properties. Examples of the phytochemicals highlighted in this review are phenolic acid, syringic acid, salicylic acid, p-coumaric acid, gallic acid, benzoic acid, caffeic acid, chrysin and its derivatives, kaempferol, fisetin, catechin, apigenin, quercetin, acacetin, pinocembrin, pinobanksin, hesperetin, naringenin, vitexin, isoorientin, xanthohumol, and galangin. This review highlights the anticancer mechanisms and molecular pathways of the phytochemicals found in Malaysian honey, focusing on their antioxidant effects, induction of mitochondrial-mediated apoptosis, inhibition of angiogenesis and metastasis, and suppression of cancer cell proliferation. The findings of various studies published in the past five years are collated to understand their mechanisms of action. Full article

Breast cancer is the most commonly diagnosed cancer among women, with approximately one in eight women developing the disease during their lifetime. Despite advancements in current treatment options, breast cancer was responsible for an estimated 670,000 deaths worldwide in 2022. This highlights the urgent need for the development of novel therapeutic strategies. Historically, plant-derived compounds have played a significant role in cancer therapy, exemplified by widely used chemotherapeutic agents such as paclitaxel and docetaxel. In recent years, increasing attention has been directed toward novel plant-derived compounds as potential anti-cancer agents. Among these, Naringenin, a flavonoid predominantly found in citrus fruits, has shown promising antioxidant, anti-inflammatory, and anti-cancer properties. This review highlights recent studies investigating the effects of Naringenin and its derivatives on breast cancer. Evidence from both in vitro and in vivo animal models suggests that Naringenin may exert anti-tumor activity by inhibiting cell proliferation, promoting apoptosis, modulating key cell signaling pathways, and enhancing radio-sensitivity in breast cancer cells. Although preclinical evidence strongly supports the anticancer potential of Naringenin in breast cancer, comprehensive clinical studies are urgently needed to validate its efficacy and safety in humans. Full article

Background/Objectives: Loquat (Eriobotrya japonica) is widely cultivated for its fruit, while its aerial by-products remain largely underexploited despite increasing interest in plant-derived bioactive compounds and sustainable food systems. This study comprehensively investigates and compares the phenolic composition and in vitro bioactivities of loquat leaves and flowers to support their potential valorisation as functional ingredients. Methods: Extractable and non-extractable polyphenolic fractions were obtained and quantified, and the extractable fraction was further characterised using HPLC-ESI-QTOF-MS. In vitro bioactivity assessment included antioxidant capacity (FRAP and ABTS), glucose dialysis retardation index, and α-glucosidase inhibition. Results: Flowers contained significantly higher levels of both extractable and non-extractable polyphenols than leaves. Qualitative and semi-quantitative phenolic profiling, including multivariate analysis, revealed clear compositional differences between the two organs. Flowers showed a higher relative abundance of phenolic acids, as well as the presence of several compounds absent in leaves, such as kaempferol, naringenin-3-O-glucoside, and three glycosilated anthocyanins. Flower-derived fractions exhibited consistently higher antioxidant activity across all phenolic fractions than leaf-derived fractions, in agreement with their greater polyphenol content. Regarding antidiabetic activity, leaf samples showed a modest capacity to delay glucose diffusion, whereas this effect was not observed in flowers. In contrast, flower extracts displayed a strong inhibitory effect against α-glucosidase, exceeding that of the reference inhibitor acarbose, while this activity was not detectable in leaf extracts under the experimental conditions. Conclusions: These findings support the revalorisation of loquat by-products, particularly flowers, as sustainable sources of bioactive compounds with potential applications in functional foods and health-related products. Full article

A naringenin-rich extract was obtained from Mexican oregano (Lippia graveolens Kunth) by supercritical CO₂ extraction and subjected to simulated gastrointestinal digestion to evaluate its potential to mitigate oxidative stress, reduce nitric oxide (NO) production, and enhance glucose uptake, an indicator of insulin resistance. Even after the simulated digestion, the extracts still showed activity, as the digested supercritical extract showed cellular antioxidant activity in colorectal adenocarcinoma (Caco-2) cells higher than 80%, increased glucose uptake in hepatocellular carcinoma HepG2 cells with insulin resistance by 29.9% and decreased NO production in 38.1% in murine macrophages (RAW 264.7). The methanolic extract showed similar results but led to higher NO production. In general, supercritical CO₂ extraction yields higher flavonoid content in oregano extract than conventional methanolic extraction, as reflected in the biological activities; moreover, the green nature of the process supports the development of functional ingredients. Full article

Cinnamomum cassia essential oil production generates substantial waste, and the therapeutic potential of non-volatile constituents from cinnamomum cassia leaves in ulcerative colitis (UC) has not been fully explored. This research focused on identifying the principal components of cinnamomum cassia leaf extract (CCLE) through ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), and its anti-inflammatory potential was verified in vitro. A lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model was employed, with assessments performed through cell viability assays, Griess assay, fluorescent probe detection, wound healing, and Transwell migration assays. Network pharmacology analysis combined with molecular docking revealed that CCLE exerts therapeutic effects against UC by targeting key molecules including TNF, TLR4, STAT3, SRC, PTGS2, NFKB1, MMP9, EGFR, BCL2, and AKT1, with high binding affinity between these targets and CCLE components (especially Quercetin, Catechin, Naringenin, 3′,4′-dimethoxyflavonol, Procyanidin Bl, and Caffeic acid). Enrichment analysis indicated that the therapeutic effect of CCLE on UC was significantly associated with the PI3K-Akt signaling pathway, B cell receptor signaling pathway, NF-κB signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway. The experimental results demonstrated that CCLE markedly reduced the production of nitric oxide (NO) and reactive oxygen species (ROS) (* p < 0.05) and inhibited macrophage migration (* p < 0.05). In conclusion, CCLE appears to ameliorate UC via a multi-target regulatory mechanism involving inflammatory signaling pathways. These outcomes offer a scientific foundation for the further development of CCLE. Full article