The effect of naringenin-phospholipid complex on thermal oxidative stability of soybean oil under heating condition.

Naringenin (NGE), a typical flavanone abundant in citrus fruits, exhibits remarkable antioxidant activities. However, its low solubility in oil restricts its widespread use in inhibiting lipid oxidation. In this study, we present a novel and effective approach to address this limitation by developing a naringenin-phospholipid complex (NGE-PC COM). Comprehensive analytical techniques including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were employed to confirm the formation of the NGE-PC COM and elucidate the interaction mechanism between NGE and phospholipids molecules. Notably, the oil-solubility of NGE was significantly enhanced by approximately 2700-fold when formulated as a phospholipid complex in soybean oil. The improved oil-solubility of NGE-PC COM enabled effective inhibition of oil thermal oxidation under high temperature conditions. Generally, this investigation proposed a novel and promising strategy for employing flavanones with strong antioxidant activities to enhance the thermal oxidative stability of edible oil during heating processes.

The anti-inflammatory activity of flavonoids and alkaloids from Sophora flavescens alleviates psoriasiform lesions: Prenylation and methoxylation beneficially enhance bioactivity and skin targeting.

The herb Sophora flavescens displays anti-inflammatory activity and can provide a source of antipsoriatic medications. We aimed to evaluate whether S. flavescens extracts and compounds can relieve psoriasiform inflammation. The ability of flavonoids (maackiain, sophoraflavanone G, leachianone A) and alkaloids (matrine, oxymatrine) isolated from S. flavescens to inhibit production of cytokine/chemokines was examined in keratinocytes and macrophages. Physicochemical properties and skin absorption were determined by in silico molecular modeling and the in vitro permeation test (IVPT) to establish the structure-permeation relationship (SPR). The ethyl acetate extract exhibited higher inhibition of interleukin (IL)-6, IL-8, and CXCL1 production in tumor necrosis factor-α-stimulated keratinocytes compared to the ethanol and water extracts. The flavonoids demonstrated higher cytokine/chemokine inhibition than alkaloids, with the prenylated flavanones (sophoraflavanone G, leachianone A) led to the highest suppression. Flavonoids exerted anti-inflammatory effects via the extracellular signal-regulated kinase, p38, activator protein-1, and nuclear factor-κB signaling pathways. In the IVPT, prenylation of the flavanone skeleton significantly promoted skin absorption from 0.01 to 0.22 nmol/mg (sophoraflavanone G vs. eriodictyol). Further methoxylation of a prenylated flavanone (leachianone A) elevated skin absorption to 2.65 nmol/mg. Topical leachianone A reduced the epidermal thickness in IMQ-treated mice by 47%, and inhibited cutaneous scaling and cytokine/chemokine overexpression at comparable levels to a commercial betamethasone product. Thus, prenylation and methoxylation of S. flavescens flavanones may enable the design of novel antipsoriatic agents.

New cyclic C-geranylflavanones isolated from Paulownia fortunei fruits with their anti-proliferative effects on three cancer cell lines.

Seven new C-geranylated flavanones, fortunones F - L (1-7), were isolated from the fresh mature fruits of Paulownia fortunei (Seem.) Hemsl. Their structures were determined by extensive spectroscopic data interpretation (UV, IR, HRMS, NMR, and CD). These new isolated compounds were all with a cyclic side chain modified from the geranyl group. Among them, compounds 1-3 all possessed a dicyclic geranyl modification, which was described firstly for Paulownia C-geranylated flavonoids. All the isolated compounds were subjected to the cytotoxic assay on human lung cancer cell A549, mouse prostate cancer cell RM1 and human bladder cancer cell T24, respectively. Results indicated A549 cell line was more sensitive to C-geranylated flavanones than the other two cancer cell lines and compounds 1, 7 and 8 exhibited potential anti-tumor effects (IC50 ˂ 10 µM). Further research revealed the effective C-geranylated flavanones could exert their anti-proliferative activity on A549 cells by inducing apoptosis and blocking cells in G1 phase.

Chiral and achiral separation of ten flavanones using supercritical fluid chromatography. Application to bee pollen analysis.

The separation of ten flavanones (flavanone, 2'-hydroxyflavanone, 4'-hydroxyflavanone, 6-hydroxyflavanone, 7-hydroxyflavanone, naringenin, naringin, hesperetin, pinostrobin, and taxifolin) using supercritical fluid chromatography and considering achiral and chiral approaches has been studied in this work. For this purpose, different stationary phases and organic modifiers have been checked. Considering the achiral separation, the best results were obtained with the Lichrospher 100 Diol column at 35 °C, 3 mL/min, 150 bar and a gradient of 2-propanol from 5% to 50%. The baseline separation of the ten compounds was achieved in 18 min. Using the chiral column Chiralpak AD, the separation of the ten pairs of enantiomers was obtained in 32 min. In this case, the chromatographic conditions were 30 °C, 3 mL/min, 150 bar and the organic modifier was a mixture ethanol/methanol (80:20) containing 0.1% of trifluoroacetic acid applied in an elution gradient from 15% to 50%. The applicability of the proposed chiral method was assessed by analysing bee pollen samples and 2S-pinostrobin was determined in some of them.

Metabolomic characterization of the chemical compositions of Dracocephalum rupestre Hance.

Maojian tea (MJT) is a traditional Chinese herbal tea beverage manufactured from the leaves of the Dracocephalum rupestre Hance plant. In this study, a nontargeted metabolomics approach combined with absolute quantifications was applied to comprehensively investigate the chemical compositions of MJT and to determine the effects of the processing methods on compounds. Flavones (apigenin and luteolin, 0.06-1.35 mg/g), flavanones (eriodictyol and naringenin, 0.1-2.3 mg/g), flavone 7-O-glycosides (0.15-5.98 mg/g), flavanone 7-O-glycosides (0.28-19.41 mg/g), and triterpenoids were presumed to be characteristic components of MJT. Applying imitative green and black tea processing methods to MJT led to increases in flavone/flavanone aglycones, lipids, and triterpenoids and decreases in flavone/flavanone glycosides, amino acids, organic acids, and most phenolic acids. This study offers novel insights into the chemical compositions and the influences of processing methods on MJT and will be utilized for the quality control of MJT.

In Vitro α-Glycosidase Inhibition and In Silico Studies of Flavonoids Isolated from Pistacia integerrima Stew ex Brandis.

The galls of Pistacia integerrima are used in folk medicine for curing diabetes. The main aim of this study was the purification of flavonoids from galls of P. integerrima. The methanolic extract was subjected to column chromatographic analysis which afforded six flavonoids, namely, 3,5,7,4'-tetrahydroxy-flavanone (1), naringenin (2), 3,5,4'-trihydroxy,7-methoxy-flavanone (3), sakuranetin (4), spinacetin (5), and patuletin (6). These isolated compounds (1-6) were tested against α-glycosidase. The maximum antagonistic effect was noted against compound 6 (97.65%) followed by compound 5 (90.42%) and compound 1 (90.01%) at the same concentration (0.2 µg). The inhibitory potential of all tested compounds was significant with a degree of variation from each other. Docking studies showed that all studied compounds interact with the active site residues via hydrogen bond interactions with hydroxyl groups, and thus, inhibition was enhanced. Hence, this finding would be the first screening of isolated flavonoids for α-glycosidase activity and with the mechanism of action. These flavonoids should be further investigated as candidate drugs for combating diabetes mellitus.

Mechanistic and therapeutic perspectives of baicalin and baicalein on pulmonary hypertension: A comprehensive review.

Pulmonary hypertension (PH) is a chronic and fatal disease, for which new therapeutic drugs and approaches are needed urgently. Baicalein and baicalin, the active compounds of the traditional Chinese medicine, Scutellaria baicalensis Georgi, exhibit a wide range of pharmacological activities. Numerous studies involving in vitro and in vivo models of PH have revealed that the treatment with baicalin and baicalein may be effective. This review summarizes the potential mechanisms driving the beneficial effects of baicalin and baicalein treatment on PH, including anti-inflammatory response, inhibition of pulmonary smooth muscle cell proliferation and endothelial-to-mesenchymal transformation, stabilization of the extracellular matrix, and mitigation of oxidative stress. The pharmacokinetics of these compounds have also been reviewed. The therapeutic potential of baicalin and baicalein warrants their continued study as natural treatments for PH.

Alpinetin: a Dietary Flavonoid with Diverse Anticancer Effects.

Cancer is a global burden and mechanistically complex disease with a plethora of genetic, physiological, metabolic, and environmental alterations. The development of dietary nutraceuticals into cancer chemotherapeutics has emerged as a new paradigm in cancer treatment. Alpinetin (ALPI) is a novel flavonoid component of multiple edible and medicinal plants and possesses a wide range of biological and pharmacological activities including antibacterial, anti-hemostatic, anti-oxidative, anti-hepatotoxic, stomachic, immunosuppressive, and anti-inflammatory. Recently, ALPI has been reported as a bioactive dietary nutraceutical with promising anticancer activity in various human cancers through multiple mechanisms. The purpose of this review is to compile the data on natural sources of ALPI, and its anticancer activity including cellular targets and anticancer mechanism in various human cancers. Moreover, this review will set the stage for further design and conduct pre-clinical and clinical trials to develop ALPI into a lead structure for oncological therapy.

Prospective multifunctional roles and pharmacological potential of dietary flavonoid narirutin.

Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength, purity, and cheap cost-effectiveness. Citrus fruits contain significant amounts of flavanones, which falls to the category of polyphenols. Flavanones occupy a major fraction of the total polyphenols present in the plasma when orange juice is taken highly or in moderate states. Narirutin is a disaccharide derivative available in citrus fruits, primarily dihydroxy flavanone. From a pharmacological viewpoint, narirutin is a bioactive phytochemical with therapeutic efficacy. Many experimental researches were published on the use of narirutin. Anticancer activity, neuroprotection, stress relief, hepatoprotection, anti-allergic activity, antidiabetic activity, anti-adipogenic activity, anti-obesity action, and immunomodulation are a couple of the primary pharmacological properties. Narirutin also has antioxidant, and anti-inflammatory activities. The ultimate goal of this review is to provide the current scenario of pharmacological research with narirutin; to make a better understanding for therapeutic potential of narirutin, as well as its biosynthesis strategies and side effects. Extensive literature searches and studies were undertaken to determine the pharmacological properties of narirutin.

A new ß-hydroxydihydrochalcone from Tephrosia uniflora, and the revision of three ß-hydroxydihydrochalcones to flavanones.

The CH2Cl2/MeOH (1:1) extract of the stems of Tephrosia uniflora yielded the new ß-hydroxydihydrochalcone (S)-elatadihydrochalcone-2'-methyl ether (1) along with the three known compounds elongatin (2), (S)-elatadihydrochalcone (3), and tephrosin (4). The structures were elucidated by NMR spectroscopic and mass spectrometric data analyses. Elongatin (2) showed moderate antibacterial activity (EC50 of 25.3 µM and EC90 of 32.8 µM) against the Gram-positive bacterium Bacilus subtilis, and comparable toxicity against the MCF-7 human breast cancer cell line (EC50 of 41.3 µM). Based on the comparison of literature and predicted NMR data with that obtained experimentally, we propose the revision of the structures of three ß-hydroxydihydrochalcones to flavanones.

Preparation of Naringenin Nanosuspension and Its Antitussive and Expectorant Effects.

Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical therapeutic effect of NRG is limited by its low bioavailability due to poor solubility. To enhance the solubility, naringenin nanosuspensions (NRG-NSps) were prepared by applying tocopherol polyethylene glycol succinate (TPGS) as the nanocarrier via the media-milling method. The particle size, morphology, and drug-loading content of NRG-NSps were examined, and the stability was evaluated by detecting particle size changes in different physiological media. NRG-NSps exhibited a flaky appearance with a mean diameter of 216.9 nm, and the drug-loading content was 66.7%. NRG-NSps exhibited good storage stability and media stability. NRG-NSps presented a sustainable release profile, and the cumulative drug-release rate approached approximately 95% within 7 d. NRG-NSps improved the antitussive effect significantly compared with the original NRG, the cough frequency was decreased from 22 to 15 times, and the cough incubation period was prolonged from 85.3 to 121.6 s. Besides, NRG-NSps also enhanced expectorant effects significantly, and phenol red secretion was increased from 1.02 to 1.45 µg/mL. These results indicate that NRG-NSps could enhance the bioavailability of NRG significantly and possess a potential clinical application.

Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation.

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative disease in the contemporary era, and it is still clinically incurable. Eriodictyol, a natural flavonoid compound that is mainly present in citrus fruits and some Chinese herbal medicines, has been reported to exert anti-inflammatory, antioxidant, anticancer and neuroprotective effects. However, few studies have examined the anti-AD effect and molecular mechanism of eriodictyol. METHODS: APP/PS1 mice were treated with eriodictyol and the cognitive function of mice was assessed using behavioral tests. The level of amyloid-ß (Aß) aggregation and hyperphosphorylation of Tau in the mouse brain were detected by preforming a histological analysis and Western blotting. HT-22 cells induced by amyloid-ß peptide (1-42) (Aß1-42) oligomers were treated with eriodictyol, after which cell viability was determined and the production of p-Tau was tested using Western blotting. Then, the characteristics of ferroptosis, including iron aggregation, lipid peroxidation and the expression of glutathione peroxidase type 4 (GPX4), were determined both in vivo and in vitro using Fe straining, Western blotting and qPCR assays. Additionally, the expression level of vitamin D receptor (VDR) and the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway were tested using Western blotting and qPCR assays. Afterward, HT-22 cells with VDR knockout were used to explore the potential mechanisms, and the relationship between VDR and Nrf2 was further assessed by performing a coimmunoprecipitation assay and bioinformatics analysis. RESULTS: Eriodictyol obviously ameliorated cognitive deficits in APP/PS1 mice, and suppressed Aß aggregation and Tau phosphorylation in the brains of APP/PS1 mice. Moreover, eriodictyol inhibited Tau hyperphosphorylation and neurotoxicity in HT-22 cells induced by Aß1-42 oligomer. Furthermore, eriodictyol exerted an antiferroptosis effect both in vivo and in vitro, and its mechanism may be associated with the activation of the Nrf2/HO-1 signaling pathway. Additionally, further experiments explained that the activation of Nrf2/HO-1 signaling pathway by eriodictyol treatment mediated by VDR. CONCLUSIONS: Eriodictyol alleviated memory impairment and AD-like pathological changes by activating the Nrf2/HO-1 signaling pathway through a mechanism mediated by VDR, which provides a new possibility for the treatment of AD.

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Coronavirus Infection.

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

Protective role of naringin loaded solid nanoparticles against aflatoxin B1 induced hepatocellular carcinoma.

This study examines the hepatoprotective activity of naringin loaded solid nanoparticles (NRG-SLNs) and compared with free naringin (FNRG) against aflatoxin B1 (AFB1) induced hepatocellular carcinoma. The liver's self-healing ability was studied using a self-recovery group that received no therapy. Following AFB1 therapy, rats were given NRG-SLNs produced using the ion-gelation technique. Histology, serum injury indicators, oxidative stress biomarkers, a pro-inflammatory response biomarker, and tumor indicators were used to evaluate the liver tumor and its responsiveness to therapy. At a dosage of 6.18 mg/kg BW, NRG-SLNs (128 ± 4 nm) provided substantially greater hepatoprotection than free NRG. The actions of NRG-SLNs were equivalent to those of silymarin (SILY), which was given at a dosage of 20 mg/kg BW. The lack of regeneration potential of liver tissue after the damage was verified by the self-recovery group. NRG's efficiency in treating hepatic cancer was increased by using SLN's approach. The increased impact is most likely due to: a) enhanced oral bioavailability, b) the regulated and sustained action of enclosed NRG, and c) a decrease in discomfort and toxicity if any after orally administered. NRG-SLNs may be considered as a therapeutic option for hepatic ailments as effectiveness post-induction of liver carcinoma, is demonstrated presently.

Hypoglycemic and hypolipidemic dual activities of extracts and flavonoids from Desmodium caudatum and an efficient synthesis of the most potent 8-prenylquercetin.

Since glucolipid metabolism disorders is often the mono-target therapy fails in managing blood glucose and lipid levels and the other complications, it is urgent and necessary to seek for the new potential drugs or functional food acting on multi-targets. The hypoglycemic and hypolipidemic dual activities of the root, stems and leaves of Desmodium caudatum, which is used for traditional Chinese medicine, was evaluated. Twelve extracts with different extraction conditions were prepared and extract 9 was find to exhibit potential inhibitory activities of fructose-1, 6-bisphosphatase (FBPase), α-glucosidase, and pancrelipase, as well as promote cellular glucose consumption and reduce cellular content of lipid. Five flavonoids were isolated and identified from extract 9, among which 8-prenylquercetin exhibited potent α-glucosidase (IC50 = 4.38 µM) and FBPase (IC50 = 3.62 µM) dual inhibitory activity, which were 75-fold higher than acarbose (IC50 = 330.10 µM) and comparable with AMP (IC50 = 2.92 µM). In addition, 8-prenylquercetin was able to promote glucose consumption and reduce lipid content. Besides, an efficient synthesis of the most potent 8-prenylquercetin was developed from inexpensive and commercially available rutin in 21% overall yield by 6 steps, which lay the foundation of preparation sufficient amount for follow-up study.

Isolation and characterization of a novel flavanone glycoside from an endemic plant Haplanthodes neilgherryensis.

The chemical characterization study of an endemic plant, Haplanthodes neilgherryensisis (Wight) R.B. Majumdar from Western Ghats of India, resulted in to the isolation of a new flavanone glycoside, 5-hydroxy-7-methoxy-8-O-ß-D-glucopyranosyl-2S-flavanone (1), along with 3 known flavonoids, 7-O-methyl dihydrowogonin (2), 7-O-methyl wogonin (3), andrographidine C (4). The structure of 1 was elucidated by using 1 D and 2 D NMR and HRMS experimental data, while for the known compounds, 1H NMR and mass spectrometry data were compared with the reported literature. Compound 1 was tested in vitro to check the improvement in uptake of glucose by the L6 rat skeletal muscle tissues and the observed EC50 value was 5.8 µM, while rosiglitazone showed EC50 of 2.7 µM.

Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review.

Natural products have historically been invaluable as a premium source of therapeutic agents. Recent advancements in genomics and structural biology have portrayed a high-resolution landscape of the diversity of proteins targeted by pharmacologically active products from natural sources. Natural product research has generated valuable wealth of information and cutting-edge research-works have leveraged our conceptual knowledge altogether to a new level. Wogonin (5,7-dihydroxy-8-methoxyflavone) is an O-methylated flavone and has attracted noteworthy appreciation because of its ability to pharmacologically target plethora of cell signaling pathways in different cancers. In this mini-review, we have gathered scattered pieces of available scientific evidence to summarize how wogonin pharmaceutically targeted Wnt/?-catenin, JAK/STAT, VEGF/VEGFR and TRAIL-driven apoptotic pathways in wide variety of cancers. We have also critically analyzed how wogonin prevented carcinogenesis and metastasis in tumor-bearing mice. Although researchers have uncovered pleiotropic role of wogonin in the regulation of different oncogenic signaling cascades but there are visible knowledge gaps in our understanding related to regulation of non-coding RNAs by wogonin. Future studies must converge on the unraveling of additional drug targets for wogonin to achieve a fuller and realistic understanding of the chemopreventive properties of wogonin.

Preparation of Hop Estrogen-Active Material for Production of Food Supplements.

In recent years, the interest in the health-promoting effects of hop prenylflavonoids, especially its estrogenic effects, has grown. Unfortunately, one of the most potent phytoestrogens identified so far, 8-prenylnaringenin, is only a minor component of hops, so its isolation from hop materials for the production of estrogenically active food supplements has proved to be problematic. The aim of this study was to optimize the conditions (e.g., temperature, the length of the process and the amount of the catalyst) to produce 8-prenylnaringenin-rich material by the magnesium oxide-catalyzed thermal isomerization of desmethylxanthohumol. Under these optimized conditions, the yield of 8-prenylnaringenin was 29 mg per 100 gDW of product, corresponding to a >70% increase in its content relative to the starting material. This process may be applied in the production of functional foods or food supplements rich in 8-prenylnaringenin, which may then be utilized in therapeutic agents to help alleviate the symptoms of menopausal disorders.

Polyphenols from Citrus Tacle® Extract Endowed with HMGCR Inhibitory Activity: An Antihypercholesterolemia Natural Remedy.

Tacle® is a citrus fruit obtained from the crossbreeding of Clementine and Tarocco cultivars. This fruit retains a promising nutraceutical potential most likely due to a high content in polyphenols, among which the main constituents are the two glycosides naringin and hesperidin. Herein, we evaluated, through an in vitro assay, the capability of Tacle extracts to inhibit the hydroxymethylglutaryl-CoA reductase enzyme, which plays a key role in cholesterol biosynthesis. The results obtained spurred us to investigate whether the anti-enzymatic activity observed may be due to a direct interaction of aglycones naringenin and hesperetin with the enzyme catalytic site. Molecular docking simulations indicated that these two compounds are able to anchor to the protein with binding modes and affinities similar to those found for statins, which represent mainstream medications against hypercholesterolemia. The overall results showed an interesting nutraceutical potential of Tacle, suggesting that its extract could be used for dietary supplementation in the treatment of moderate hypercholesterolemia.

Breast cancer suppression by curcumin-naringenin-magnetic-nano-particles: In vitro and in vivo studies.

BACKGROUND: The limitations of surgery, radiotherapy, and chemotherapy in cancer treatment and the increase in the application of nanomaterials in the field of biomedicine have promoted the use of nanomaterials in combination with radiotherapy for cancer treatment. OBJECTIVE: To improve the efficiency of cancer treatment, curcumin-naringenin loaded dextran-coated magnetic nanoparticles (CUR-NAR-D-MNPs) were used as chemotherapy and in combination with radiotherapy to verify their effectiveness in treating tumors. METHODS: CUR-NAR-D-MNPs were prepared and studied by several characterization methods. Median inhibitory concentration (IC50) and cellular toxicity were evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell death and radiosensitization were studied by acridine orange/ethidium bromide dual staining of MCF-7 human breast cancer cells. RESULTS: CUR-NAR-D-MNPs induce apoptosis and inhibited cell proliferation through reactive oxygen species (ROS) generation. CUR-NAR-D-MNPs used alone had a certain therapeutic effect on tumors. CUR-NAR-D-MNPs plus radiotherapy significantly reduced the tumor volume and led to cell cycle arrest and induction of apoptosis through modulation of P53high, P21high, TNF-αlow, CD44low, and ROShigh signalingCONCLUSIONS:CUR-NAR-D-MNPs are effective in the treatment of tumors when combined with radiotherapy, and show radiosensitization effects against cancer proliferation in vitro and in vivo.