Search

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti‐inflammatory properties. This study aimed to investigate the effect of luteolin on IS‐mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM‐1) and monocyte chemoattractant protein (MCP‐1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03‐fold, p < 0.05), ICAM‐1 (by 2.19‐fold, p < 0.05) and MCP‐1 protein expression (by 2.18‐fold, p < 0.05), and HL‐60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS‐induced ROS production, ICAM‐1 and MCP‐1 protein expression, and HL‐60 cell adhesion. Moreover, luteolin attenuated IS‐induced nuclear accumulation of p65 and c‐jun. Luteolin dose‐dependently increased heme oxygenase‐1 (HO‐1) expression and the maximum fold induction of HO‐1 by luteolin was 3.68‐fold (p < 0.05), whereas, HO‐1 knockdown abolished the suppression of ICAM‐1 and MCP‐1 expression by luteolin. Luteolin may protect against IS‐induced vessel damage by inducing HO‐1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF‐κB) and activator protein 1 (AP‐1) mediated ICAM‐1 and MCP‐1 expression. [ABSTRACT FROM AUTHOR]

Ocimum tenuiflorum, commonly known as Tulsi, is revered in Ayurveda for its extensive medicinal properties. However, there is a need to consolidate current knowledge on its phytochemical constituents and their pharmacological activities to identify potential areas for further research and drug development. This review aims to bridge this gap by providing a comprehensive analysis of the bioactive secondary metabolites found in O. tenuiflorum, such as rosmarinic acid, oleanolic acid, luteolin, ursolic acid, and limonene, and their associated therapeutic effects. The review will highlight the pharmacological importance of these metabolites, which exhibit antioxidant, neuroprotective, anticancer, and anti‐inflammatory properties. Additionally, this study will explore the plant's wide range of beneficial qualities, including anti‐inflammatory, antioxidant, anticholinergic, pain‐relieving, antimicrobial, stress‐reducing, antidiabetic, anticancer, liver‐protective, ulcer‐inhibiting, antifungal, and wound‐healing attributes. Furthermore, this review focuses on the plant's potential in treating conditions such as asthma, persistent fever, tuberculosis, malaria, skin discoloration, itching, digestive issues, hemorrhoids, bone fractures, gout, urinary tract infection, and diabetes. By reviewing the current literature, the aim is to identify the gaps in the existing research and propose directions for future studies. This comprehensive review will serve as a valuable resource for researchers in the development and investigation of novel drugs derived from O. tenuiflorum. [ABSTRACT FROM AUTHOR]

Hypoxic diabetic foot ulcers (HDFUs) pose a challenging chronic condition characterized by oxidative stress damage, bacterial infection, and persistent inflammation. This study introduces a novel therapeutic approach combining ergothioneine (EGT), luteolin (LUT), and quaternized chitosan oxidized dextran (QCOD) to address these challenges and facilitate wound healing in hypoxic DFUs. In vitro, assessments have validated the biosafety, antioxidant, and antimicrobial properties of the ergothioneine‐luteolin‐chitin (QCOD@EGT‐LUT) hydrogel. Furthermore, near‐infrared II (NIR‐II) fluorescence image‐guided the application of QCOD@EGT‐LUT hydrogel in simulated HDFUs. Mechanistically, QCOD@EGT‐LUT hydrogel modulates the diabetic wound microenvironment by reducing reactive oxygen species (ROS). In vivo studies demonstrated increased expression of angiogenic factors mannose receptor (CD206) and latelet endothelial cell adhesion molecule‐1 (PECAM‐1/CD31), coupled with decreased inflammatory factors tumor necrosis factor‐α (TNF‐α) and Interleukin‐6 (IL‐6), thereby promoting diabetic wound healing through up‐regulation of transforming growth factor β‐1 (TGF‐β1). [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Knockdown of THOC1 reduces the proliferation of hepatocellular carcinoma and increases the sensitivity to cisplatin." The author identified errors in two images in the original article, but these errors do not affect the overall results, discussion, or conclusion of the article. The corrected figures are provided in the correction notice. The publisher remains neutral with regard to jurisdictional claims and institutional affiliations. [Extracted from the article]

Vascular endothelial damage due to ionizing radiation is the main pathological process of radiation injury and the main cause of damage to various organs in nuclear accidents. Ferroptosis plays an important role in ionizing radiation-induced cell death. We have previously reported that luteolin is highly resistant to ferroptosis. In the present study, body weight, microvessel count, H&E, and Masson staining results showed that luteolin rescued radial vascular injury in vivo. Cell Counting Kit 8 (CCK8), Giemsa staining clarified the anti-ferroptosis ability of luteolin with low toxicity. Malondialdehyde (MDA), superoxide dismutase (SOD), NADP+/NADPH, Fe2+ staining, dihydroethidium (DHE) and MitoTracker assays for ferroptosis-related metrics, we found that luteolin enhances human umbilical vein endothelial cells (HUVECs) antioxidant damage capacity. Drug affinity responsive target stability (DARTS), surface plasmon resonance (SPR), computer simulated docking and western blot showed that heat shock protein beta-1 (HSPB1) is one of the targets of luteolin action. Luteolin inhibits ferroptosis by promoting the protein expression of HSPB1/solute carrier family 7 member 11 (SLC7A11)/ glutathione peroxidase 4 (GPX4). In conclusion, we have preliminarily elucidated the antioxidant damage ferroptosis ability and the target of action of luteolin to provide a theoretical basis for the application of luteolin in radiation injury diseases. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by sustained fibrotic lesions. Orally administered drugs usually fail to efficiently penetrate the interstitial tissue and reach the lesions, resulting in low treatment efficiency. Luteolin (Lut) is a natural flavonoid, active metabolites of which possess antioxidant, anti‐inflammatory, anti‐fibrotic, and anti‐apoptotic properties. In this study, a nano‐formulation is developed by loading Lut into hyaluronidase nanoparticles (Lut@HAase). These Lut@HAase nanoparticles (NPs) exhibit small size and good stability, suitable for noninvasive inhalation and accumulation in the lungs, and hyaluronidase at the site of lesions can degrade hyaluronic acid in the interstitial tissue, enabling efficient penetration of Lut. Lut's therapeutic effect, when administered via NPs, is studied both in vitro (using MRC5 cells) and in vivo (using IPF mice models), and its anti‐fibrotic properties are found to inhibit inflammation and eliminate reactive oxygen species. Conclusively, this study demonstrates that Lut@HAase can improve lung function and enhance survival rates while reducing lung damage with few abnormalities during IPF treatment. [ABSTRACT FROM AUTHOR]

In this work, agaric derived porous carbon (A-dPC) was obtained through high-temperature pyrolysis of biomass soaked in HNO3 solution as a carbon source, and zinc oxide nanorods (r-ZnO) were synthesized by a hydrothermal method. A-dPC and r-ZnO were combined under ultrasound to form zinc oxide nanorods/agaric derived porous carbon nanocomposites (r-ZnO/A-dPCNs). The A-dPC, r-ZnO and r-ZnO/A-dPCNs were characterized utilizing X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer–Emmett–Teller (BET). The r-ZnO/A-dPCNs/GCE showed good electrocatalytic activity in the detection of acetaminophen (PA), dopamine (DA) and luteolin. Under the optimal conditions, the sensor is capable of detecting PA and DA contemporaneously, has a wide linear range (0.10 μM–200.0 μM and 0.10 μM–100.0 μM) and low detection limits of 0.033 μM to PA and 0.022 μM to DA and meanwhile, it also can be used to detect luteolin with a wide linear range (0.010 μM–80.0 μM) and low detection limit (0.0012 μM). In addition, the sensor can be applied to detect PA, DA and luteolin in actual samples, and it exhibits good selectivity and stability. [ABSTRACT FROM AUTHOR]

Luteolin is a natural flavonoid, which exists in many plants, including onions, broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary flavonoid with potent uric acid‐lowering and antioxidant bioactivities. To date, the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still needs to be better defined. This study aims to evaluate the therapeutic efficacy of luteolin in a preclinical mouse model and in vitro. Luteolin was administered in the HN mice induced by the combination of potassium oxonate and hypoxanthine to evaluate the potential renoprotective effects in vivo. The NRK‐52E cells were stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin staining, biochemical analysis, immunoblotting, immunofluorescence, and immunohistochemistry were performed for the histopathologic and mechanistic investigations. The results suggest that luteolin attenuated tubular dilation and epithelial atrophy in the renal tissue of HN mice. Further, luteolin improved biochemical indicators concerning renal functions and oxidative stress in vivo. Mechanistically, luteolin reduced the renal expressions of KIM‐1 and caspase‐3. Luteolin activated renal SIRT1/6 cascade and its downstream Nrf2‐mediated antioxidant pathway. Furthermore, luteolin elevated the renal expressions of ATP‐binding cassette subfamily G isoform 2 protein (ABCG2) and organic anion/cation transporters. In addition, livers of luteolin‐treated HN mice exhibited robust inhibition of xanthine oxidase. Together, our study shows that luteolin alleviates renal injury in the HN mice by activating urate excretion and Nrf2/HO‐1/NQO1 antioxidant pathways and inhibiting liver xanthine oxidase activity. Thus, luteolin may be a potential agent for the treatment of HN. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dandelion contains hundreds of active compounds capable of inhibiting urease activity, but the individual compounds have not yet been fully identified, and their effects and underlying mechanisms are not clear. The present study aimed to screen the urease inhibition active compounds of dandelion by urease inhibitory activity evaluation HPLC‐tandem mass spectrometry analysis, their mechanism of urease inhibition by polyphenols was explored using enzyme kinetic studies via Lineweaver‐Burk plots. Other investigations included isothermal titration calorimetry and surface plasmon resonance sensing, fluorescence quenching experiments, and single ligand molecular docking and two‐ligand simultaneous docking techniques. RESULTS: The results indicated that the ethyl acetate fraction of dandelion flower exhibited the greatest inhibition (lowest IC50 0.184 ± 0.007 mg mL−1). Chlorogenic acid, caffeic acid and luteolin could be effective urease inhibitors that acted in a non‐competitive inhibition manner. Individually, chlorogenic acid could not only fast bind to urease, but also dissociate rapidly, whereas luteolin might interact with urease with the weakest affinity. The chlorogenic acid‐caffeic acid combination exhibited an additive effect in urease inhibition. However, the chlorogenic acid‐luteolin and caffeic acid‐luteolin combinations exhibited antagonistic effects, with the caffeic acid‐luteolin combination showing greater antagonism. CONCLUSION: The present study reveals that chlorogenic acid, caffeic acid and luteolin are major bioactive compounds for urease inhibition, indicating the molecular mechanisms. The antagonistic effects were observed between luteolin and chlorogenic acid/caffeic acid, and the interactions of the catalytic site and flap may account for the antagonistic effects. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Luteolin is an essential natural polyphenol found in a variety of plants. Numerous studies have supported its protective role in neurodegenerative diseases, yet the research for its therapeutic utility in D-galactose (D-gal)-induced brain ageing is still lacking. In this study, the potential neuroprotective impact of luteolin against D-gal-induced brain ageing was explored. Forty rats were randomly divided into four groups: control, luteolin, D-gal, and luteolin-administered D-gal groups. All groups were subjected to behavioural, cholinergic function, and hippocampal mitochondrial respiration assessments. Hippocampal oxidative, neuro-inflammatory, senescence and apoptotic indicators were detected. Gene expressions of SIRT1, BDNF, and RAGE were assessed. Hippocampal histopathological studies, along with GFAP and Ki67 immunoreactivity, were performed. Our results demonstrated that luteolin effectively alleviated D-gal-induced cognitive impairment and reversed cholinergic abnormalities. Furthermore, luteolin administration substantially mitigated hippocampus oxidative stress, mitochondrial dysfunction, neuro-inflammation, and senescence triggered by D-gal. Additionally, luteolin treatment considerably attenuated neuronal apoptosis and upregulated hippocampal SIRT1 mRNA expression. In conclusion, our findings revealed that luteolin administration attenuated D-gal-evoked brain senescence, improving mitochondrial function and enhancing hippocampal neuroregeneration in an ageing rat model through its antioxidant, senolytic, anti-inflammatory, and anti-apoptotic impacts, possibly due to upregulation of SIRT1. Luteolin could be a promising therapeutic modality for brain aging-associated abnormalities. [ABSTRACT FROM AUTHOR]

Background: Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection, anti-cancer, antioxidants, anti-inflammatory, neuroprotective, etc. According to its hepatoprotective properties, luteolin was selected to co-treat with sorafenib, one of the approved protein kinase inhibitors, to reduce sorafenib-induced normal liver cell damage. Methods: The BRL-3A cell line was treated with sorafenib to establish a liver injury model, followed by luteolin treatment. The cell viability was detected, and the mechanism of action was detected by immunofluorescence, western blotting, and real-time quantitative PCR. Results: The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT (SLC7A11) and glutathione peroxidase 4 (GPX4) expression and display a chelating effect on iron, which led to increased glutathione and decreased malondialdehyde, Fe2+ and lipid reactive oxygen species contents in BRL-3A cells, and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited. In addition, when sorafenib caused the accumulation of lipid reactive oxygen species, luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2 (Nrf2) and up-regulating the expression of the associated genes heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1). Conclusion: Therefore, luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity. It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background/Objectives: Luteolin (LUT) is a natural flavonoid with known anti-inflammatory, antioxidant, and anti-cancer properties. Cervical cancer, particularly prevalent in certain regions, remains a significant health challenge due to its high recurrence and poor response to treatment. This study aimed to investigate the anti-tumor effects of LUT on human cervical epidermoid carcinoma cells (Ca Ski), focusing on cell growth inhibition, apoptosis induction, and regulation of mitochondrial membrane potential. Methods: Ca Ski cells were treated with varying concentrations of LUT (0, 25, 50, 100 µM) for different time periods (24, 48, 72 hours). Cell viability was measured using the MTT assay, apoptosis was assessed by flow cytometry with annexin V-FITC/PI staining, and changes in mitochondrial membrane potential were evaluated using JC-1 staining. Caspase-3 activation was examined by flow cytometry, and expression of apoptosis-related proteins (caspase-3, -8, -9, AIF) was analyzed via Western blotting. Results: LUT significantly inhibited the growth of Ca Ski cells in a dose- and time-dependent manner, with the most pronounced effects observed at 100 µM over 72 hours. Flow cytometry confirmed that LUT induced apoptosis without causing necrosis. Mitochondrial membrane potential was reduced after LUT treatment, coinciding with increased caspase-3 activation. Western blot analysis revealed the upregulation of pro-apoptotic proteins caspase-3, -8, -9, and AIF, indicating that LUT induces apoptosis through the intrinsic mitochondrial pathway. Conclusions: Luteolin effectively inhibits cervical cancer cell proliferation and induces apoptosis by disrupting mitochondrial membrane potential and activating caspases. These findings suggest that LUT holds potential as a therapeutic agent for cervical cancer, with further studies needed to explore its in vivo efficacy and broader clinical applications. [ABSTRACT FROM AUTHOR]

The present study focused on the quantitative determination of active compounds, antioxidant and antibacterial activities of leaf extracts of different Sonneratia species. The tested species including Sonneratia alba (SA), Sonneratia caseolaris (SC), and Sonneratia ovata Backer (SO) were collected from Can Gio Mangrove Forest, Vietnam. The methanol extract of SA leaves was found to contain the highest content of total flavonoids, total phenolics and gallic acid (4344.16 ± 51.78 μg/g dry mass). The highest luteolin‐7‐O‐glucoside and luteolin amounts (5963.28 ± 59.77 and 234.33 ± 10.41 μg/g dry mass, respectively) were found in the methanol extract of SC leaves according to HPLC‐DAD analysis. The methanol extracts of all three species exhibited strong DPPH radical scavenging activity while the ethanol extracts provided strong antibacterial activity against Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. By fractionating the extracts over a SiO2 column using CHCl3: EA: MeOH gradients, the fractions containing high purity luteolin and luteolin‐7‐glucoside from SC and high purity luteolin from SO were collected. Moreover, all fractions demonstrated significant DPPH free radical scavenging ability but the fraction enriched in gallic acid showed the highest activity. These findings show that SA is a promising source of gallic acid while SC can be potentially used for the extraction and isolation of luteolin‐7‐glucoside. [ABSTRACT FROM AUTHOR]

Intestinal lymphatic transport offers an alternative and effective way to deliver drugs, such as avoiding first-pass metabolism, enhancing oral bioavailability, and facilitating the treatment of targeted lymphoid-related diseases. However, the clinical use of luteolin (LUT) is limited by its poor water solubility and low bioavailability, and enhancing lymphatic transport by nanoemulsion may be an efficient way to enhance its oral bioavailability. The objective of this work is to prepare the luteolin nanoemulsions (LUT NEs), optimized its preparation parameters by using Box-Behnken design optimization (BBD) and evaluated it in vitro and in vivo. An Caco-2 / Raji B cell co-incubation monolayer model was established to simulate the M-cell pathway, and the differences in the transmembrane transport of LUT and NEs were compared. Cycloheximide (CHX) was utilized to establish rat chylomicron (CM) blocking model, and for investigating the influence of pharmacokinetic parameters in rats thereafter. The results showed that LUT NEs have good stability, the particle sizes were about 23.87 ± 0.57 nm. Compared with LUT suspension, The Papp of LUT NEs was enhanced for 3.5-folds, the oral bioavailability was increased by about 2.97-folds. In addition, after binding with chylomicron, the oral bioavailability of LUT NEs was decreased for about 30% (AUC 0–∞ (μg/L*h): 5.356 ± 1.144 vs 3.753 ± 0.188). These results demonstrated that NEs could enhance the oral absorption of luteolin via lymphatic transport routes. [ABSTRACT FROM AUTHOR]

Mixed metal oxides derived from a metal–organic framework (MOF) sacrificial template take advantage of the original morphology of MOFs, excellent electrocatalytic properties, mesoporous structure, and more active sites and transport channels, which is favorable to construct a high-performance electrochemical sensor. Here, polyhedral CoZn-MOFs are synthesized by precipitation at room temperature, and then they are etched using Ni2+ to obtain hollow polyhedral NiCoZn hydroxide (NiCoZn-OH) nanocages. After self-assembly with graphene oxide (GO) nanosheets and annealing, the hollow polyhedral NiCoZn mixed metal oxide/reduced graphene oxide (NiCoZnOX/rGO) mixture with a size of ∼700 nm is obtained and used for electrochemically detecting luteolin (LU), which shows a high sensitivity (7.16 μA·μM–1·cm–2 in 0–60 μM) and a low limit of detection (64 nM, S/N = 3). Moreover, it has excellent selectivity in the presence of ascorbic acid and is successfully used to detect LU in diluted human urine, indicating a great potential in clinical applications. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the morphological and histological characteristics of three-dimensional cell spheroids derived from the uveal melanoma (UM) cell line C918 and assess the impact of luteolin on their cell viability. Methods: C918 cells were cultured in ultra-low adsorption 96-well plates, and morphological changes in C918 three-dimensional cell spheroids were observed over varying time intervals. Histological features of C918 multicellular spheroids cultured in ultra-low adsorption 6-well plates were examined using both HE staining and immunohistochemical staining. The CCK8 reagent was employed to measure the optical density at a 450 nm wavelength after 72-h treatments with varying luteolin concentrations in both two-dimensional and three-dimensional cultured C918 cells. The IC50 values were compared between the two culture conditions. Results: Over time in culture, the volume of C918 three-dimensional cell spheroids gradually increased, and an ischemic- and hypoxic-like region became evident within the spheroids on days 4 to 6 of culture. Histological staining demonstrated positive expression of cell viability marker antibodies (Ki67) and melanoma marker antibodies (MelanA, HMB45, S-100) in the multicellular spheroids from three-dimensional culture. CCK-8 experiments revealed that the IC50 values for luteolin in C918 cells were 183.50 μmol/L in three-dimensional culture and 16.19 μmol/L in two-dimensional culture after 72 h. Three-dimensional cultured C918 cells, treated with varying luteolin concentrations for 72 h, were observed under a microscope. The maximum cross-sectional area showed no statistically significant differences between the groups, but it was reduced in comparison to the control group. Conclusion: Three-dimensional cultured C918 cell spheroids exhibit histological characteristics similar to real tumors and are less responsive to luteolin than their two-dimensional counterparts. They offer a valuable model for anti-tumor drug screening. [ABSTRACT FROM AUTHOR]

Introduction: Luteolin, a natural compound commonly used in traditional Chinese medicine, shows clinical potential as an anti--liver cancer agent. The mechanisms underlying the anti--liver cancer effect of luteolin are limited versus those reported for other cancers. Accordingly, this study was conducted to bridge the existing knowledge gap. Methods: Transcriptomic and proteomic analyses of the response of the hepatocellular carcinoma cell line HuH-7 to luteolin were conducted, and a possible pathway was elucidated using confocal laser scanning microscopy (CLSM), flow cytometry, western blotting, qRT-PCR and bio-layer interferometry assay to systematically explore the possible mechanisms underlying the inhibition of the proliferation of liver cancer cells by luteolin. Results and Discussion: Results showed that luteolin significantly inhibited HuH-7 cell proliferation. Transcriptomic and proteomic analyses collectively revealed that luteolin could promote cell cycle arrest and apoptosis in HuH-7 cells through transcription factors p53, nuclear factor kappa B (NF-kB), FOXO, ATF2, and TCF/LEF via AKT1, as well as the KEAP-NRF and SRC-STAT3 pathways. Furthermore, AKT1 and SRC were identified as the 2 targets of luteolin. Nuclear translocation of transcription factors p53 and NF-kB were affected by luteolin administration. Additionally, AKT1 activity affected normal metabolism in HuH-7 cells and resulted in the accumulation of reactive oxygen species, which activated MOMP and further promoted apoptosis. Our results systematically elucidate the mechanism of luteolin in inhibiting the proliferation of liver cancer cells, mainly through cell cycle arrest and apoptosis via targeting AKT1 and SRC. [ABSTRACT FROM AUTHOR]

Lenvatinib is a first-line therapy for the treatment of hepatocellular carcinoma (HCC), an active multi-target tyrosine kinase inhibitor (TKI). The interaction between Traditional Chinese Medicine (TCM) and chemicals has increasingly become a research hotspot. The objective of this study was to pinpoint the effects of three flavonoids on the metabolism of lenvatinib. Enzyme reaction system was established and optimized in vitro, and in vivo experiments were conducted in Sprague-Dawley (SD) rats, where the analytes were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/ MS). We found that among three flavonoids, luteolin and myricetin had strong inhibitory effects on lenvatinib metabolism, with half-maximal inhibitory concentration (IC50) values of 11.36 ± 0.46 µM and 11.21 + 0.81 µM in rat liver microsomes (RLM), respectively, and 6.89 ± 0.43 µM and 12.32 + 1.21 µM in human liver microsomes (HLM), respectively. In Sprague-Dawley rats, the combined administration of lenvatinib and luteolin obviously expanded the exposure to lenvatinib; however, co-administered with myricetin did not have any changes, which may be due to the poor bioavailability of myricetin in vivo. Furthermore, the inhibitory type of luteolin on lenvatinib showed an un- competitive in RLM and a mixed in HLM. Collectively, flavonoids with liver protection, especially luteolin, may inhibit lenvatinib metabolism in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Recently, acrylamide (Acr), which is a chemical compound utilised in industry, was detected in food rich in carbohydrates that had been subjected to a high temperature. It exerts its toxic effect through generation of oxidative species. Luteolin (Lut) is a potent antioxidant flavonoid that may mitigate this toxic effect. Aim to the Work: To evaluate the histochemical changes induced by Acr on adult rat epididymal caput and the probable role of Lut in ameliorating these changes. Materials and Methods: 30 adult rats were allocated into: group I (Control) received either distilled water (subgroup IA) or corn oil (subgroup IB), group II received 100 mg/kg/day of Lut orally, group III received 6.25 mg/kg/day of Acr orally, and group IV co-administrated Lut and Acr at doses as those of groups II and III. After 21 days, the rats were sacrificed after being weighed at the start and the end of the experiment. Sera were obtained for detection of testosterone level. Caudal fluid was collected for sperm count and motility analysis. Tissue homogenates were used to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), and the gene expression of Bcl2-Associated X Protein (BAX) and B-cell lymphoma 2 (Bcl2). Caputs were processed and examined by light and electron microscopies. All data were subjected to statistical analyses. Results: Acr induced disruption of the caput epithelium with widening of the intercellular spaces, vacuolations, nuclear changes, reduction in sperm count and motility, a significant decline in animal weights, serum testosterone, increase in MDA and reduction in SOD. Moreover, gene expression of BAX showed a significant up-regulation with down-regulation of Bcl2. Co-administration of Lut with Acr led to improvement in structure of epididymal caput, the animal weights, the testosterone level, SOD, Bcl2, sperm count and motility. Conclusion: Acr induced histochemical toxicity in epididymal caput, meanwhile Lut attenuated this effect. [ABSTRACT FROM AUTHOR]

Objective To develop a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of five flavonoids in Ganmao’an granules (GMA). Methods Chromatographic separation was achieved on a Kromasil C18 Column (150 mm× 4.6 mm,5 μm,100 Å), which was eluted with methanol (A) -0.1% formic acid (B) at the flow rate of 1.0 ml/min. The gradient condition was as follows: 0-20 min, 35% A, and 20-40 min, 45% A. The column temperature was 25 °C. Analytes were detected using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in the negative ion scanning. The multiple reaction monitoring mode was used for qualitative analysis. For each flavonoid, two precursor ion/product ion transitions were chosen: lutin m/z 609.1→300.1, hyperin and isoquercitrin m/z 463.0→300.1, quercetin m/z 301.0→151.0, luteolin m/z 285.0→132.9. Results Five flavonoids showed the good relationships within their own concentration ranges (correlation coefficient r>0.999 1), whose average recoveries were in the range of 100.63%-102.81% with RSDs of 0.67%-2.07%. The content results of rutin, hyperoside, isoquercetin, quercetin, and luteolin in 10 batches of GMA were 32.23-479.83, 0.291-1.825, 11.44-20.54, 6.32-18.41, 3.46-6.51 μg/g, respectively. Conclusion The results indicated that the developed method was sensitive, accurate and could provide excellent specificity for simultaneous determination of five flavonoids in GMA. [ABSTRACT FROM AUTHOR]

Aspergillus flavus, a fungus known for producing aflatoxins, poses significant threats to agriculture and global health. Flavonoids, plant-derived compounds, inhibit A. flavus proliferation and mitigate aflatoxin production, although the precise molecular and physical mechanisms underlying these effects remain poorly understood. In this study, we investigated three flavonoids—apigenin, luteolin, and quercetin—applied to A. flavus NRRL 3357. We determined the following: (1) glycosylated luteolin led to a 10% reduction in maximum fungal growth capacity; (2) quercetin affected cell wall integrity by triggering extreme mycelial collapse, while apigenin and luteolin caused peeling of the outer layer of cell wall; (3) luteolin exhibited the highest antioxidant capacity in the environment compared to apigenin and quercetin; (4) osmotic stress assays did not reveal morphological defects; (5) flavonoids promoted cell adherence, a precursor for biofilm formation; and (6) RNA sequencing analysis revealed that flavonoids impact expression of putative cell wall and plasma membrane biosynthesis genes. Our findings suggest that the differential effects of quercetin, luteolin, and apigenin on membrane integrity and biofilm formation may be driven by their interactions with fungal cell walls. These insights may inform the development of novel antifungal additives or plant breeding strategies focusing on plant-derived compounds in crop protection. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder. Methods: HD N171‐82Q transgenic and WT mice received luteolin or vehicle for treatment at 6 weeks of age. The mice's body weight changes and survival rates were monitored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates. Results: Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle‐treated HD group. Furthermore, the luteolin‐treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin‐treated HD mice compared to the vehicle‐treated HD group. Conclusion: Luteolin holds promise as a therapeutic agent for improving survival outcomes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interventions that reverse HD pathology or slow down its progression. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease (AD) is a neurodegenerative disorder with limited treatment options. This study aimed to investigate the therapeutic effects of Ginkgo biloba leaf extract (GBE) on AD and explore its potential mechanisms of action. Methods: Key chemical components of GBE, including quercetin, luteolin, and kaempferol, were identified using network pharmacology methods. Bioinformatics analysis revealed their potential roles in AD through modulation of the PI3K/AKT/NF‐κB signaling pathway. Results: Mouse experiments demonstrated that GBE improved cognitive function, enhanced neuronal morphology, and reduced serum inflammatory factors. Additionally, GBE modulated the expression of relevant proteins and mRNA. Conclusion: GBE shows promise as a potential treatment for AD. Its beneficial effects on cognitive function, neuronal morphology, and inflammation may be attributed to its modulation of the PI3K/AKT/NF‐κB signaling pathway. These findings provide experimental evidence for the application of Ginkgo biloba leaf in AD treatment and highlight its potential mechanisms of action. [ABSTRACT FROM AUTHOR]

Diabetic encephalopathy (DE) is a severe complication of the central nervous system associated with diabetes. In this study, we investigated the regulatory role of mammalian target of rapamycin (mTOR) on nuclear factor κB (NF-κB) in mice with DE, and the neuroprotective effect and therapeutic mechanisms of luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties. The results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE. It also decreased the levels of phosphorylated mTOR, phosphorylated NF-κB, and histone deacetylase 2 (HDAC2) and increased the expression of brain-derived neurotrophic factor and synaptic-related proteins. Furthermore, protein-protein interaction and the Gene Ontology analysis revealed that luteolin was involved in the regulatory network of HDAC2 expression through the mTOR/NF-κB signaling cascade. Our bioinformatics and molecular docking results indicated that luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR/NF-κB signaling inhibition. Analysis of luteolin's target proteins and their interactions suggest an effect on HDAC2 and cognition. In conclusion, HDAC2 and tau hyperphosphorylation are regulated by the mTOR/NF-κB signaling cascade in DE, and luteolin is found to reverse these effects, demonstrating its protective role in DE. Article Highlights: Luteolin's neuroprotective effect on diabetic encephalopathy (DE) targets mTOR/NF-κB signaling. Decreases in phosphorylated mTOR, phosphorylated NF-κB, and HDAC2, and increases in brain-derived neurotrophic factor and synaptic proteins were demonstrated. Luteolin's potential direct targeting to HDAC2 is highlighted, providing a new approach for DE treatment. [ABSTRACT FROM AUTHOR]

Chemotherapy plays a crucial role in the clinical treatment of triple‐negative breast cancer (TNBC), but drug resistance limits its clinical application. The active ingredients of Chaihu Shugan Powder (CSP; Bupleurum Liver‐Coursing Powder), quercetin and luteolin, both belong to flavonoid compounds and have significant anti‐tumor potential, which can promote chemotherapy sensitivity. However, the correlation between the two and TNBC paclitaxel (PTX) chemotherapy sensitivity is unknown. We collected herbal components of CSP from the TCMSP database, and screened effective molecules and corresponding targets. STRING database was utilized to construct a protein–protein interaction network combining effective molecules and target genes. The top 50 nodes ranked by affinity were chosen for subsequent functional analysis, and the drug‐active ingredient‐gene interaction network was established using Cytoscape software. Molecular docking was used to determine the small molecules that target TNBC PTX resistance. The "clusterProfiler" package was utilized for GO and KEGG enrichment analyses on the top 50 genes to determine the pathways affected by CSP. Cell counting and colony formation assays evaluated cell viability, IC50 values, and proliferation capacity. Flow cytometry tested PTX intracellular accumulation. Western blot assayed the expression of TNF pathway‐related proteins. Active ingredients of CSP, quercetin and luteolin, could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization. Quercetin and luteolin repressed the TNF signaling pathway and promoted PTX chemotherapy sensitization. Quercetin and luteolin could inhibit TNBC cell proliferation and promote PTX chemotherapy sensitization through the TNF signaling pathway. Therefore, the use of quercetin and luteolin plus PTX treatment provides a prospective strategy for TNBC treatment. [ABSTRACT FROM AUTHOR]

Luteolin (LN), is an herbal bioactive flavone and exhibits many pharmacological activities. However, the bioavailability of LN is limited due to its inadequate solubility and significant first-pass metabolism. The present study developed transdermal LN-loaded invasomes (IVM) gel to improve the therapeutic efficacy. The LN-IVM was prepared and optimized by 2³ factorial designs. LN-IVM was characterized for physicochemical parameters. The optimized LN-IVM (LN-IVMopt) was incorporated into HPMC-K4M gel and evaluated for viscosity, spreadability, and irritation. Further LN-IVM gel was evaluated for drug release, ex-vivo permeation, pharmacokinetic and pharmacodynamics study. LN-IVMopt showed 300.8±2.67 nm of VS, 0.258 of PDI, 89.92±1.29% of EE, and a zeta potential of -18.2 mV. LN-IVM exhibited spherical morphology. FTIR and XRD results demonstrated that LN was encapsulated into IVM matrix. The optimized IVM gel (LN-IVMoptG2) exhibited excellent viscosity, spreadability, and sustained release of LN (91.32±2.95% in 24 h). LN-IVMoptG2 exhibited statistically significant (p < 0.05) higher flux (5.79 µg/h/cm²) than LN-gel (2.09 µg/h/cm²). The apparent permeability coefficient of plain LN gel and LN- IVMoptG was 1.15X10-5 cm/min and 3.22x10-5 cm/min respectively. LN-IVMoptG2 showed no irritation (score 0.0) throughout the study (60 min). The relative bioavailability of LN from LN-IVMopt-G2 (transdermal) was 2.38±0.19 fold as compared to LN-Sus (oral) and 1.81±0.15-fold than plain LN-gel (transdermal). The LN-IVMoptG2 showed a substantial lessening in the paw volume up to 12 h (17.48±1.94% swelling) than plain LN-gel (44.77±2.82% swelling). The finding concluded that the IVM gel is a novel, effective, and safe approach for the delivery of LN transdermally to improve its therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fisetin and Luteolin are important flavonoids produced in plants and known for their antioxidant, anti-inflammatory, neuroprotective, and analgesic properties. They are also good candidates for different types of biosensors. The model used to describe the fluorescence (FL) emission of these flavonoids involves an excited-state intermolecular proton transfer (ESIPT) process that causes a change in the molecule configuration and a corresponding decrease in the emission energy. Due to the different molecular structures of Fisetin and Luteolin, only one possible proton transfer within the molecule is allowed for each of them: transfer of the H3 proton for Fisetin and of the H5 for Luteolin. Here, we compare their calculated emission wavelengths, obtained using TDDFT/M06-2X/6-31++G(d,p), with their FL emission spectra measured on the corresponding powders and solutions and show that the experimental data are consistent with the presence of the ESIPT process. We also compare the emission wavelengths found for Fisetin and Luteolin with those calculated and measured for Quercetin, where, under photoexcitation, the transfers of both H3 and H5 protons are possible. We analyze the difference in the processes associated with the H3 and H5 proton transfers and discuss the reason for the predominance of the H5 proton transfer in Quercetin. Additionally, a new system of notation for flavonoid molecules is developed. [ABSTRACT FROM AUTHOR]

Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti‐tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour‐bearing mice. luteolin effectively inhibited the growth of solid tumours in a well‐established mouse model of HCC. High‐throughput sequencing revealed that luteolin treatment could enhance T‐cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8+ T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour‐infiltrating CD8+ T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour‐infiltrating CD8+ T lymphocytes in H22 tumour‐bearing mice. The CD8+ T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN‐γ and TNF‐α in serum. The combined administration of luteolin and the PD‐1 inhibitor enhanced the anti‐tumour effects in H22 tumour‐bearing mice. Luteolin could exert an anti‐tumour immune response by inducing CD8+ T lymphocyte infiltration and enhance the anti‐tumour effects of the PD‐1 inhibitor on H22 tumour‐bearing mice. [ABSTRACT FROM AUTHOR]

Long COVID is a major health concern because many patients develop chronic neuropsychiatric symptoms, but the precise pathogenesis is unknown. Matrix metalloproteinase-9 (MMP-9) can disrupt neuronal connectivity and be elevated in patients with long COVID.

Diabetic ureteral injury (DUI) is a condition characterized by damage to the ureter, causing functional and morphological changes in the urinary system, which have a significant impact on a quality of life and requires appropriate medical treatment. The present study describes to novel design of luteolin (LT), a type of natural flavonoid, encapsulated selenium nanoparticles (Se NPs) to attain therapeutic potential for DUI. The physico-chemical characterizations of prepared Se NPs have benefitted zeta potential (−18 mV) and particle size (10–50 nm). In vitro assays were demonstrated the potential of LT-SeNPs by HEK 293 cells stimulated by STZ for DUI. Cytotoxicity assays on HEK 293 and NIH-3T3 showed >90% cell viability, which demonstrates the suitability of the nanoformulation for DUI treatment. The LT-SeNPs significantly inhibits the NLRP3 inflammasome through Nrf2/ARE pathway, which benefits for DUI treatment. The developed LT-SeNPs could be an effective formulation for the DUI therapy.

BACKGROUND: Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury; however, the specific mechanism is still not clear. Therefore, revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE: To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS: Allen’s impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group. The serum of rats of each group was collected. H9c2 cells were divided into a blank control group, a sham operated rat serum group, a spinal cord injury rat serum group and a luteolin pretreatment group. The cells in blank control group were only cultured with ordinary culture medium. The cells in the sham operated rat serum group were treated with medium containing 10% serum from sham operated rat. The cells in the spinal cord injury rat serum group were treated with medium containing 10% serum from spinal cord injury rat. The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10% rat serum from spinal cord injury rat. After 24 hours of culture, the survival rate of each group of H9c2 cells was measured by CCK-8 assay. Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION: Compared with the blank control group, there was no significant change in cell survival rate in the sham operated rat serum group (P > 0.05). Compared with the sham operated rat serum group, the cell survival rate (P < 0.01) and the expression of LC3 protein (P < 0.05) in spinal cord injury rat serum group was significantly reduced, and the expression of p62 protein was significantly increased (P < 0.05). Compared with the spinal cord injury rat serum group, the survival rate of cells in the luteolin pretreatment group significantly increased (P < 0.000 1); the expression of LC3 protein significantly increased (P < 0.05), and the expression of p62 protein significantly decreased (P < 0.05). The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy. [ABSTRACT FROM AUTHOR]

Objective(s): In this study, we assessed the impact of luteolin (LUT) on mood disorders (specifically anxiety and depression) induced by sleep deprivation (SD) by regulating pathways associated with neuroinflammation.Materials and Methods: Rapid eye movement (REM) SD was employed to induce anxiety and depression in the animal subjects. The animals were treated with PAX (15 mg/kg, positive control) and LUT (10 and 20 mg/kg) for a duration of 21 days. The anxiety and depressive disorders were evaluated using behavioral tests. Following the sacrifice of the animals, hippocampal tissues were stored for molecular investigations.Results: SD resulted in anxiety, as evidenced by the elevated plus maze test and open field test. Furthermore, the findings from the sucrose performance test, forced swimming test, and tail suspension test confirmed the presence of depressive-like behaviors in the animals. The nuclear factor kappa B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome components, including apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), NLRP3, and active Caspase-1, were up-regulated in the hippocampus (HC) of the animals subjected to REM SD. However, treatment with LUT demonstrated a significant reversal of the behavioral changes by modulating the NF-κB and NLRP3 inflammasome components in the HC.Conclusion: It can be concluded that LUT demonstrated antidepressant effects via regulation of the NF-κB/NLRP3 inflammasome axis components in the HC.

Abstract Context There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear. Objective Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD. Methods The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein–protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments. Results Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. Discussion and conclusion The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy.

Abstract Background Luteolin (Lut), a flavonoid present in the daily diet, exhibits potent anti-inflammatory and renoprotective effects. However, the association between Lut and chronic kidney disease (CKD) remains uncertain. The objective of this study is to explore the potential correlation. Methods A total of 2,393 CKD patients were enrolled in a prospective cohort in the National Health and Nutrition Examination Survey (NHANES). A 24-h dietary recall was utilized to estimate the intake of dietary Lut based on the type and amount of food consumed. The National Death Index mortality data was utilized to ascertain all-cause and cardiac mortality (as of December 27, 2023). Cox proportional hazards model was used to estimate the relationship between Lut intake and mortality risk. Results The median Lut intake was 0.305 mg/day, with interquartile range was 0.105–0.775 mg/day. During the follow-up period (median, 93 months), 682 all-cause deaths (217 cardiovascular disease [CVD] deaths) were recorded. Per unit increase in Lut intake reduced all-cause mortality by 27% (P

Abstract Background Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. Results We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. Conclusions Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

Han Luo,1,&ast; Xiaofei Wang,1,&ast; Mengqi Fang,1 Huifan Yu,1 Lili Gui,1 Zhengkun Wu,1 Jianyong Sheng,2 Fei Li1 1Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Hubei University of Medicine, 30 Renmin South Road, Shiyan, Hubei, 442000, People’s Republic of China, Email piaopodexinlifei@163.comIntroduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1± 16.8 nm, zeta potential of about − 23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.Keywords: Hydroxyethyl starch, nanocrystals, stabilizer, luteolin, oral bioavailability, anti-hyperuricemia

ABSTRACT Investigating the inheritance and genetic variation of luteolin content in peanut shells is pivotal for developing improved cultivars with high luteolin content. In this study, we developed a genetic map spanning 976.8 cM using 115 highly advanced recombinant inbred lines (RILs) and the Axiom_Arachis array containing 58K single‐nucleotide polymorphisms (SNPs). Quantitative trait locus (QTL) analysis was then performed using phenotype data from 2‐year field trials. From these analyses, we identified three significant QTLs with 4.1%–11.7% phenotypic variation explained (PVE) for luteolin content in peanut shells. We further identified five candidate genes with putative functions suggesting possible involvement in plant flavonoid and terpenoid biosynthetic pathways in peanut luteolin biosynthesis. Additionally, two new peanut inbreeding lines with high luteolin and oleic acid levels were selected and are expected to be used as multifunctional genomic backgrounds for future breeding and research programs. The information on the QTL regions and candidate genes from the present study could be very useful for developing new peanut cultivars with high luteolin content and for identifying the genetic/genomic determinants of luteolin content in peanut shells. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of luteolin on the proliferation, apoptosis, migration and glycolysis of human hepatocellular carcinoma cell lines and to explore their mechanism. Methods HepG2 and Huh7 cells cultured in vitro were divided into two groups. Cells in the control group were treated with DMEM medium, and cells in the experimental groups were treated with 20，40，60，80 and 100 µmol/L luteolin, respectively. Cell proliferation rate was measured by CCK-8 assay. The number of cell clones formed was detected by the cell clone formation experiment to evaluate the cell proliferation ability. The relative expression levels of apoptosis-related proteins (Bax, Bcl-2, and Caspase-3 proteins) were measured by Western blotting to evaluate the apoptosis ability. The cell migration rate was measured by the cell scratch test to evaluate the cell migration ability. The glucose consumption and lactic acid production levels were determined by the kit. Glycolysis-related proteins (GLUT4, PDK1, HK2, PKM2, and LDHA proteins) were detected by Western blotting to evaluate the cell glycolysis ability. Western blotting was used to detect the LKB1/AMPK signaling pathway-related proteins (LKB1/P-LKB1 and AMPK/P-AMPK protein ratios). Results Compared with the control group, the proliferation rates of HepG2 and Huh7 cells in the experimental group decreased in a time- and dose-dependent manner； the number of colony-forming cell colonies of HepG2 and Huh7 cells in the experimental group decreased in a dose-dependent manner (all P<0. 05). Compared with the control group, the relative expression levels of Bax and Caspase-3 proteins in HepG2 and Huh7 cells in the experimental group increased, and the relative expression of Bcl-2 protein decreased in a dose-dependent manner (all P<0. 05). Compared with the control group, the migration rates of HepG2 and Huh7 cells in the experimental group decreased in a time- and dose-dependent manner (both P<0. 05). Compared with the control group, the glucose consumption of HepG2 and Huh7 cells in the experimental group (except for the dose of 20 µmol/L) decreased, and the lactate production increased in a dose-dependent manner； the relative expression levels of GLUT4, PDK1, HK2, PKM2 and LDHA proteins in HepG2 and Huh7 cells in the experimental group decreased in a dose-dependent manner (all P<0. 05). Compared with the control group, the protein expression ratios of LKB1/P-LKB1 and AMPK/ P-AMPK in the experimental group increased in a dose-dependent manner (both P<0. 05). Conclusions Luteolin inhibits the glycolysis process of human hepatocellular carcinoma cell lines, further inhibits cell proliferation, migration and promotes apoptosis in a dose- or time-dependent manner, and the mechanism may be related to the activation of intracellular LKB1/AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5‐fluorouracil (5‐FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5‐FU with Lut in PDACs. Methods and Results: PDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5‐FU. The xenograft tumors of DPYD‐overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA‐seq analysis of the DPYD‐overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity—MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5‐FU on DPYD‐overexpressing xenograft tumors and PDAC of Pdx1‐Cre; LSL‐KrasG12D/+; Trp53flox/flox(KPPC) mice. Neither single administration of 5‐FU nor Lut showed significant inhibitory effects; however, the combined administration of 5‐FU and Lut exhibited a significant tumor‐suppressive effect in both the xenograft tumors and KPPC models. Conclusion: We have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5‐FU resistance, in PDACs. The combination therapy of Lut and 5‐FU holds the potential for enhanced efficacy against PDACs. [ABSTRACT FROM AUTHOR]

Context: There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear. Objective: Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD. Methods: The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein–protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments. Results: Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. Discussion and conclusion: The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 was first discovered in 2019 and has disseminated throughout the globe to pandemic levels, imposing significant health and economic burdens. Although vaccines against SARS-CoV-2 have been developed, their long-term efficacy and specificity have not been determined, and antiviral drugs remain necessary. Flavonoids, which are commonly found in plants, fruits, and vegetables and are part of the human diet, have attracted considerable attention as potential therapeutic agents due to their antiviral and antimicrobial activities and effects on other biological activities, such as inflammation. The present study uses a combination of biochemical, cellular, molecular dynamics, and molecular docking experiments to provide compelling evidence that the flavonoid luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one) has antiviral activity against SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) that is synergistically enhanced by magnesium, zinc, and vitamin C. The IC50 of luteolin against 2 μM 3CLpro is 78 μM and decreases 10-fold to 7.6 μM in the presence of zinc, magnesium, and vitamin C. Thermodynamic stability analyses revealed that luteolin has minimal effects on the structure of 3CLpro, whereas metal ions and vitamin C significantly alter the thermodynamic stability of the protease. Interactome analysis uncovered potential host-virus interactions and functional clusters associated with luteolin activity, supporting the relevance of this flavone for combating SARS-CoV-2 infection. This comprehensive investigation sheds light on luteolin's therapeutic potential and provides insights into its mechanisms of action against SARS-CoV-2. The novel formulation of luteolin, magnesium, zinc, and vitamin C may be an effective avenue for treating COVID-19 patients. [ABSTRACT FROM AUTHOR]

Chronic sinusitis is a persistent inflammatory condition needing better treatment options with fewer side effects to reduce recurrence. Luteolin, a flavonoid found in various plants, exhibits anti-inflammatory and anti-allergic properties. This study explores luteolin's impact on chronic sinusitis. We isolated human nasal epithelial cells from sinusitis patients and used lipopolysaccharide-induced cells as a model. High-mobility group box 1 protein was notably elevated in these patients. Our findings suggest that luteolin can suppress the expression of inflammatory cytokines induced by lipopolysaccharide in these cells. Additionally, luteolin was able to inhibit the epithelial--mesenchymal transition in the treated cells. This inhibitory effect on high-mobility group box 1 expression led to reduced inflammation and transition processes. Overall, luteolin could potentially be an effective treatment for chronic sinusitis, minimizing inflammation and cellular transition in nasal epithelial cells. [ABSTRACT FROM AUTHOR]

Introduction: Mast cells are known for their involvement in allergic reactions but also in inflammatory reactions via secretion of numerous pro-inflammatory chemokines, cytokines, and enzymes. Drug development has focused on antiproliferative therapy for systemic mastocytosis and not on inhibitors of mast cell activation. The only drug available as a "mast cell blocker" is disodium cromoglycate (cromolyn), but it is poorly absorbed after oral administration, is a weak inhibitor of histamine release from human mast cells, and it develops rapid anaphylaxis. Instead, certain natural flavonoids, especially luteolin, can inhibit mast cell activation. Methods: Here, we compared pretreatment (0–120 min) with equimolar concentration (effective dose for 50% inhibition = 100 mm for inhibition of histamine release by cromolyn) of cromolyn and luteolin on release of mediators from the cultured human LADR mast cell line stimulated either by immunoglobulin E (IgE) and anti-IgE or with IL-33. Results: We show that luteolin is significantly more potent than cromolyn inhibiting release of histamine, tryptase, metalloproteinase-9, and vascular endothelial growth factor. Moreover, while luteolin also significantly inhibited release of IL-1β, IL-6, and IL-8 (CXCL8) and TNF, cromolyn had no effect. Conclusion: These findings support the use of luteolin, especially in liposomal form to increase oral absorption, may be a useful alternative to cromolyn. [ABSTRACT FROM AUTHOR]

Luteolin (Lu), a compound with various biochemical and pharmacological activities beneficial to human health, has attracted researchers' attention. This study proposes an efficient and scalable method using ultrasound to intercalate graphene oxide (GO)-coated silica spheres (SiO2) into MXenes, resulting in a 3D conductive interconnected structural composite material. Characterization of the composite material was conducted using SEM, TEM, XRD, XPS, and Raman spectroscopy. MXenes exhibit excellent electrical conductivity, and the SiO2@GO surface with abundant hydroxyl and silanol groups provides high-binding active sites that facilitate Lu molecule enrichment. The formation of the 3D conductive interconnected structural composites enhances charge transport, significantly improving sensor sensitivity. Consequently, the sensor demonstrates excellent detection capabilities (detection range 0.03–7000 nM, detection limit 12 pM). Furthermore, the sensor can be applied to quantitative determination of Lu in real samples, including chrysanthemums, Jiaduobao, honeysuckle, purple perilla, and peanut shells, achieving recoveries between 98.2 and 104.7%. [ABSTRACT FROM AUTHOR]

Our research investigates LXSWD's therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms. Methods: Network pharmacology was utilized to identify LXSWD's key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions. Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD's role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea's inflammation alterations (p < 0.05). Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD's potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea. [ABSTRACT FROM AUTHOR]

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant and anti‐inflammatory properties, but whether they inhibit lipotoxicity‐mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages and Kupffer cells stimulated with 100 μM palmitate (PA) in the presence or absence of 20 μM of each flavone. PA increased p‐PERK, p‐IRE1α, p‐JNK1/2, CHOP, and TXNIP as well as p62 and LC3‐II expression and induced autophagic flux damage. Caspase‐1 activation and IL‐1β release were also noted after 24 h of exposure to PA. In the presence of the PERK inhibitor GSK2656157, PA‐induced CHOP and TXNIP expression and caspase‐1 activation were mitigated. Compared with PA treatment alone, Bcl‐2 coupled to beclin‐1 was elevated and autophagy was reversed by the JNK inhibitor SP600125. With luteolin, apigenin, and chrysin treatment, PA‐induced ROS production, ER stress, TXNIP expression, autophagic flux damage, and apoptosis were ameliorated. Moreover, TXNIP binding to NLRP3 and IL‐1β release in response to LPS/PA challenge were reduced. These results suggest that luteolin, apigenin, and chrysin protect hepatic macrophages against PA‐induced NLRP3 inflammasome activation and autophagy damage by attenuating endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a type of malignant tumor originating from the intrahepatic, periportal, or distal biliary system. The treatment means for CCA is limited, and its prognosis is poor. Spatholobi Caulis (SC) is reported to have effects on anti-inflammatory and anti-tumor, but its role in CCA is unclear. First, the potential molecular mechanism of SC for CCA treatment was explored based on network pharmacology, and the core targets were verified by molecular docking and molecular dynamics simulation. Then, we explored the inhibitory effect of SC on the malignant biological behavior of CCA in vitro and in vivo and also explored the related signaling pathways. The effect of combination therapy of SC and cisplatin (DDP) in CCA was also explored. Finally, we conducted a network pharmacological study and simple experimental verification on luteolin, one of the main components of SC. Network pharmacology analysis showed that the core targets of SC on CCA were AKT1, CASP3, MYC, TP53, and VEGFA. Molecular docking and molecular dynamics simulation indicated a good combination between the core target protein and the corresponding active ingredients. In vitro, SC inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. In vivo experiments, the results were consistent with in vitro experiments, and there was no significant hepatorenal toxicity of SC at our dosage. Based on KEGG enrichment analysis, we found PI3K/AKT signaling pathway might be the main signaling pathway of SC action on CCA by using AKT agonist SC79. To explore whether SC was related to the chemotherapy sensitivity of CCA, we found that SC combined with DDP could more effectively inhibit the progression of cholangiocarcinoma. Finally, we found luteolin may inhibit the proliferation and invasion of CCA cells. Our study demonstrates for the first time that SC inhibits the progression of CCA by suppressing EMT through the PI3K-AKT signaling pathway, and SC could enhance the effectiveness of cisplatin therapy for CCA. [ABSTRACT FROM AUTHOR]

Copyright of Food & Fermentation Industries is the property of Food & Fermentation Industries and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study reports on the physicochemical and antioxidant properties of propolis samples from various regions across Western Australia and identifies some phenolic constituents using high-performance thin-layer chromatography (HPTLC). Total phenolic content (TPC) was determined using a modified Folin–Ciocalteu assay, and antioxidant activity was investigated with the Ferric Reducing Antioxidant Power (FRAP) assay and also visualised and semi-quantified by HPTLC-DPPH analysis. TPC values ranged from 9.26 to 59.3 mg gallic acid equivalent/g of raw propolis and FRAP assay data from 4.34 to 53.8 mmol Fe2+ mmol/kg of raw propolis, although some of these variations might be related to differences in extraction yields obtained with 70% ethanol. The presence of luteolin, taxifolin, naringenin, and 4-hydroxyphenylacetic acid was confirmed based on a comprehensive, validated matching approach against an HPTLC-derived database. The findings of the study highlight the importance of future research on the chemical composition and bioactivity of Western Australian propolis. [ABSTRACT FROM AUTHOR]