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In this study, luteolin (LUT) was used as an emulsifier, benzyl isothiocyanate (BITC) as a model of nutrient delivery, and different oils [corn oil (CO), linseed oil (LO), and Antarctic krill oil (AKO)] with different carbon chain lengths and unsaturated double bond numbers as oil phases to construct Pickering emulsions. The rheological properties, photostability, storage stability, microstructure, oxidation stability, and BITC retention of Pickering emulsions were investigated to clarify the effects of different oil phases with carbon chain length and unsaturated double bond content on the properties of LUT-based Pickering emulsions. Results showed that the photostability of LUT-based Pickering emulsion was not affected by the different carbon chain lengths and unsaturated double bond content in the oil phases. Compared with LUT-CO and LUT-LO Pickering emulsion, LUT-AKO Pickering emulsion had the highest apparent viscosity and most uniform spatial structure. After 14 days of storage, the average particle size of LUT-AKO Pickering emulsion was the smallest [(213.47±2.30) nm], and the absolute value of Zeta potential and the embedding rate of BITC were the highest, reaching (42.73±1.96) mV and (65.25±1.45)%, respectively. The oxidation stability of LUT-AKO Pickering emulsion was slightly lower than those of other Pickering emulsions because of the strong AKO reactive activation. This study identified that AKO with a longer carbon chain was more suitable for preparing stable Pickering emulsions. This research provides a theoretical reference for expanding the application of LUT-based Pickering emulsions with different oil phases. [ABSTRACT FROM AUTHOR]

Background: Periapical lesions are characterized by periapical inflammation and damage to periapical tissues and eventually lead to bone resorption and even tooth loss. H2O2 is widely used in root canal therapy for patients with periapical inflammation. Luteolin possesses high anti-inflammatory, antioxidant, and anticancer potential. However, the underlying mechanism of the efficacy of H2O2 and luteolin on oxidative stress and inflammatory tissue has not been previously addressed. We aimed to investigate the anti-inflammatory and antioxidative effects of luteolin on H2O2-induced cellular oxidative inflammation. Methods: After human osteoblasts (hFOB1.19) were treated with lipopolysaccharide (LPS), luteolin, or H2O2, cell proliferation was analysed by using a cell counting kit-8 (CCK-8), cell apoptosis was measured by using flow cytometry, the production of reactive oxygen species (ROS) was evaluated by using an oxidation-sensitive probe DCFH-DA ROS assay kit, and the expression of genes and proteins was detected by using reverse transcription quantitative polymerase chain reaction (RT‒qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: We demonstrated that inflammation is closely related to oxidative stress and that the oxidative stress level in the inflammatory environment is increased. Luteolin inhibited the H2O2-induced increase in the expression of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor α (TNF-α) and significantly repressed the H2O2-induced increase in ROS, as well as markedly strengthened superoxide dismutase (SOD) activity in hFOB1.19 cells. Moreover, we detected that luteolin may inhibit H2O2-induced hFOB1.19 cell injury by suppressing the NF-κB pathway. Conclusion: We elucidated that luteolin protected human osteoblasts (hFOB1.19) from H2O2-induced cell injury and inhibited the production of proinflammatory cytokines by suppressing the NF-κB signalling pathway. Our findings provide a potential drug for treating H2O2-induced periodontitis and cell injury. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant (MDR) bacteria have become a major challenge for global healthcare systems. The search for antibacterial compounds from plants has received increasing attention in the fight against MDR bacteria. As a medicinal and edible plant, Lophatherum gracile Brongn. (L. gracile) has favorable antibacterial effect. However, the main antibacterial active compound and its antimicrobial mechanism are not clear. Here, our study first identified the key active compound from L. gracile as luteolin. Meanwhile, the antibacterial effect of luteolin was detected by using the broth microdilution method and time-kill curve analysis. Luteolin can also cause morphological structure degeneration and content leakage, cell wall/membrane damage, ATP synthesis reduction, and downregulation of mRNA expression levels of sulfonamide and quinolones resistance genes in multidrug-resistant Escherichia coli (MDR E. coli). Furthermore, untargeted UPLC/Q-TOF-MSbased metabolomics analysis of the bacterial metabolites revealed that luteolin significantly changed riboflavin energy metabolism, bacterial chemotaxis cell process and glycerophospholipid metabolism of MDR E. coli. This study suggests that luteolin could be a potential new food additive or preservative for controlling MDR E. coli infection and spread. [ABSTRACT FROM AUTHOR]

Luteolin is a widely studied flavonoid recognized for its ability to sensitize multidrug-resistant cells and anti-cancer properties. However, its clinical applications is hindered by challenges arising from its limited solubility and bioavailability. To address this issue, a synergistic approach combiningluteolin with vitamin E TPGS (TPGS) and poloxamer (Pol) was explored to boost tumour apoptosis and suppress P-glycoprotein. This study aimed to optimize luteolin-loaded TPGS/Pol micelles developed using the film hydration method, followed by lyophilization. Various key factors including the drug: polymer ratio and the TPGS: Pol ratio were examined, with encapsulation efficiency (EE) assessed using a UV-Vis spectrophotometer and particle size measured via dynamic light scattering (DLS). The results revealed that the optimized micelle composed of 1:5 drug: polymer ratio and a TPGS: Pol ratio of 3:1, exhibited a particle size below 40 nm, along with EE of 90%. Additionally, there was a notable increase of 459-fold in the solubility of luteolin-loaded micelle in comparison to pure luteolin in water. The TPGS/Pol micelles demonstrated a critical micelle concentration (CMC) of 0.0008 mg/ml, and release studies indicated sustained release behaviour for luteolin loaded micelles. In conclusion, this study has presented the feasibility of TPGS/Pol micelles in improving the therapeutic potential of luteolin, showcasing improvements in EE, particle size, solubility and sustained release behaviour. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective • To explore and analyze the efficacy of luteolin on the proliferation and apoptosis of cerebral glioma and its possible mechanism, providing a theoretical basis for luteolin in glioma treatment. Methods • The cell line of Human cerebral glioma U87 was utilized for our current research. The study group were added with 0, 20, 40, and 80 μmol/L luteolin, respectively. Luteolin’s Inhibitory function in the proliferation of U87 cells was detected by CCK-8, the Transwell chamber test was used to measure cell migration and invasion, while flow cytometry was used to assess apoptosis and Western Blot to gauge the expression of JNK/STAT3 pathway proteins. Results • In comparison with the control group, the intervention of various doses of luteolin could effectively inhibit glioma cell proliferation, the inhibitory rate uplifted remarkably with an increase of dose as well as intervention time (95% CI. 92.160-107.494, P < .05), which presented a significant time and dose dependence. The apoptosis rate of the low-dose, medium-dose, and high-dose categories was higher than that of the comparison group after 2 days of luteolin intervention (P < .05), and the apoptosis rate appeared to increase with the increase in intervention dose (P < .05). After 2 days of luteolin intervention, there were significantly more migratory and invasive cells in 3 categories than that in the control group (P < .05), and the number increased as the luteolin intervention dose was raised (P < .05). Bax and Cyt-c expressions dropped after 2 days of luteolin treatment when compared with the control set (P < .05), and the expression of Bax and Cyt-c fell considerably with increasing luteolin dose. Bcl-2, Caspase-3 and PARP expressions were significantly elevated in comparison to the control group (P < .05), and the increase was more obvious with the rise of the luteolin dose. Conclusion • Luteolin has a good inhibiting function on the proliferation of glioma cells, inhibiting cellular invasion and migration and promoting the apoptosis of glioma cells and the expression of apoptosis-related proteins, which has laid a good foundation for the application of luteolin to treat glioma cells. [ABSTRACT FROM AUTHOR]

As a widely distributed plant in Northeast China, Carex meyeriana Kunth (CMK) is generally considered to have antibacterial properties; however, there is a lack of scientific evidence for this. Therefore, we investigated the chemical composition of CMK extract and its effect against C. albicans. A total of 105 compounds were identified in the alcohol extracts of CMK by UPLC-Q-TOF-MS. Most were flavonoids, with Luteolin being the most represented. Among them, 19 compounds are found in the C. albicans lysates. After treatment with CMK ethanol extract, a significant reduction in the number of C. albicans colonies was observed in a vaginal douche solution from day 5 (p < 0.05). Furthermore, the CMK extract can reduce the number of C. albicans spores. The levels of IL-4, IL-6, IL-10, IL-1β, and TNF-α in vaginal tissues all exhibited a significant decrease (p < 0.05) compared to those in the model group as determined by ELISA. The results of HE staining showed that CMK extract can eliminate vaginal mucosa inflammation. CMK adjusts the vaginal mucosa cells by targeting twenty-six different metabolites and five specific metabolic pathways in order to effectively eliminate inflammation. Simultaneously, the CMK regulates twenty-three types of metabolites and six metabolic pathways against C. albicans infection. So, CMK strongly inhibits the growth of C. albicans and significantly reduces vaginal inflammation, making it a promising candidate for treating C. albicans infection. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows a strong correlation between type 2 diabetes mellitus, mitochondrial dysfunction, and oxidative stress. We evaluated the effects of dietary peanut shell extract (PSE) supplementation on mitochondrial function and antioxidative stress/inflammation markers in diabetic mice. Fourteen db/db mice were randomly assigned to a diabetic group (DM in AIN-93G diet) and a PSE group (1% wt/wt PSE in AIN-93G diet) for 5 weeks. Six C57BL/6J mice were fed with an AIN-93G diet for 5 weeks (control group). Gene and protein expression in the liver, brain, and white adipose tissue (WAT) were determined using qRT-PCR and Immunoblot, respectively. Compared to the control group, the DM group had (i) increased gene and protein expression levels of DRP1 (fission), PINK1 (mitophagy), and TNFα (inflammation) and (ii) decreased gene and protein expression levels of MFN1, MFN2, OPA1 (fusion), TFAM, PGC-1α (biogenesis), NRF2 (antioxidative stress) and IBA1 (microglial activation) in the liver, brain, and WAT of db/db mice. Supplementation of PSE into the diet restored the DM-induced changes in the gene and protein expression of DRP1, PINK1, TNFα, MFN1, MFN2, OPA1, TFAM, PGC-1α, NRF2, and IBA1 in the liver, brain, and WAT of db/db mice. This study demonstrates that PSE supplementation improved mitochondrial function in the brain, liver, and WAT of db/db mice, in part due to suppression of oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Purpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN. Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified. Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-β, IL-1β, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPKα (Th172) while simultaneously down-regulated the protein expression of p-NF-B (p65), NLRP3, TGF-β 1, α-SMA, and Collagen I. Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-β signaling pathway. [ABSTRACT FROM AUTHOR]

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Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti‐convulsion, diabetes control, anti‐inflammatory, neuroprotection, anti‐oxidation, anti‐cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF‐κB, toll‐like receptor, MAPK, Wnt/β‐catenin, PI3K/Akt, AMPK/mTOR, and Nrf‐2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT. [ABSTRACT FROM AUTHOR]

Introduction: Luteolin (LTL) is the primary active ingredient in honeysuckle, which exhibited wide pharmacological activities, including heat-clearing, detoxifying, anti-inflammatory and anti-oxidant effects. The conventional method for the extraction of LTL consumed a substantial amount of time and organic solvents, and poor selectivity. Therefore, fabrication of novel material with simple preparation process, low cost and excellent selectivity is of great significance for the extraction and enrichment of LTL from honeysuckle. Results: In this system, a novel surface imprinting polymer for luteolin, denoted as Fe3O4@SiO2@MIP, was synthesized using covalent-noncovalent synergistic imprinting strategies. 3-acrylamidephenylboric acid was adopted as covalent functional monomer, deep eutectic solvent (choline chloride/methacrylic acid (ChCl/MAA, 1/2, n/n)) and methacrylic acid as the non-covalent functional monomers, and Fe3O4@SiO2 nanoparticles as the magnetic support. The resultant Fe3O4@SiO2@MIP displayed a uniform morphology, good crystallinity, and excellent magnetic properties. Meanwhile, the binding experiments demonstrated that Fe3O4@SiO2@MIP exhibited high binding performance and the maximum adsorption capacity was 20.97 mg/g. Moreover, the selectivity and reusability behavior of them were satisfactory. In addition, this polymer, serving as an adsorbent, presented practical application potential in separation and enrichment of LTL from honeysuckle. Conclusion: The covalent-noncovalent synergistic imprinting strategy could greatly facilitate the preparation of imprinted nanoparticles for the specific recognition of LTL, providing a valuable approach for the enrichment of LTL in complex samples. [ABSTRACT FROM AUTHOR]

Summary: Obesity is becoming a top global health problem. Inhibition of digestive enzymes is an effective approach in weight management due to the reduction of energy absorption. In this study, the inhibitory effects of luteolin on α‐glucosidase and pancreatic lipase were investigated in vitro and in vivo via enzyme kinetics, fluorescence quenching, molecular docking and rat experiments. The results showed that luteolin inhibited α‐glucosidase and pancreatic lipase in a mixed‐type and uncompetitive manner with IC50 values of 29.31 and 42.74 μg mL−1 respectively. The binding of luteolin with the two enzymes caused the quenching of intrinsic fluorescence of protein. Molecular docking simulation revealed that luteolin could be located in the active pocket of α‐glucosidase and interact with the key amino acid residues. Moreover, a hydrophobic interaction and a van der Waals force were formed between luteolin and the key amino acid residues of pancreatic lipase (His264 and Ser153). In vivo studies further confirmed that luteolin could significantly decrease the absorption of glucose and triacylglyceride in rats by inhibiting α‐glucosidase and pancreatic lipase. [ABSTRACT FROM AUTHOR]

Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (Zostera muelleri, Halodule uninervis, Cymodocea rotundata, Syringodium isoetifolium, and Thalassia hemprichii) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of Z. muelleri had the highest activity (half minimal concentration of inhibition (IC50) = 138 µg/mL), with the aerial parts (IC50 = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC50 ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of Z. muelleri significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (1), luteolin (2), and apigenin (3) as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1β, and IL-6 and represent some of the major bioactive components of Z. muelleri aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of Z. muelleri and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation. [ABSTRACT FROM AUTHOR]

The flavone luteolin and the flavonol quercetin naturally occur in plants, providing some resistance against herbivores. However, despite suggesting the potential use of these compounds for plant protection, research on their relationship with aphids is limited. The aim of our study was to assess the effect of applying two flavonoids, quercetin and luteolin, at different concentrations, in vitro on the feeding behavior of the black bean aphid Aphis fabae Scopoli (Hemiptera: Aphididae). In most events associated with stylet activity, differences in probing behavior did not vary between the control gel and those with flavonoids. Higher concentrations of quercetin increased the number of penetrations, while lower concentrations of luteolin prolonged the first probing. The addition of flavonoids to the gels reduced passive ingestion. At a concentration of 0.1%, luteolin completely stopped salivation, and at 0.01%, it shortened the average duration of this activity. In events associated with active ingestion, differences in feeding behavior were observed between the control gel and those with quercetin at lower concentrations, affecting the time to the first stylet activity and the average time of active ingestion. Lower concentrations of luteolin prolonged the time to the first active ingestion, the duration of the first active ingestion, and the average time of this activity. Increased concentrations of quercetin and luteolin negatively affected aphid feeding behavior. Quercetin was better tolerated by A. fabae. A more noticeable effect was observed with an increase in luteolin concentration on the feeding behavior of A. fabae. These findings could be applied in biotechnological projects aiming to develop plants resistant to aphids and other herbivores. [ABSTRACT FROM AUTHOR]

This study aimed to extract apigenin and luteolin from celery seeds using 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) based ultrasonic-assisted technique. Optimal extraction conditions were determined through the integration of support vector regression combined with various optimization algorithms, including Genetic Algorithm, Particle Swarm Optimization, Gray Wolf Optimizer, Bat Algorithm, Firefly Algorithm, and Cuckoo Search Algorithm. The identified optimal conditions included an extraction time of 52 min, an HP-β-CD concentration of 24 mg/mL, and a solvent-to-solid ratio of 24 mL/g. Under these conditions, the predicted apigenin and luteolin content in the extract were 0.156 and 0.814 mg/g, respectively, closely aligning with the actual values of 0.158 ± 0.005 mg/g and 0.807 ± 0.008 mg/g. Notably, the HP-β-CD/water extract exhibited significantly higher concentrations of active ingredients and antioxidant activity compared to the water extract, with the content of apigenin and luteolin in the water extract being only 25 and 45%, respectively, compared to the HP-β-CD/water extract. Regarding the antioxidant effect, the water extract displayed a 50% scavenging capacity (SC50) of 331.29 ± 20.5 g/mL, whereas the SC50 for the HP-β-CD/water extract was 89.04 ± 4.70 g/mL. Molecular modeling and IR spectra analysis also suggested the formation of inclusion complexes between HP-β-CD and apigenin/luteolin. These findings suggested that HP-β-CD could be a preferable alternative to conventional solvents due to its advantages, such as easier control, safety, and cost-effectiveness. In addition, the use of support vector regression and nature-inspired optimization algorithms could be promising alternatives to traditional response surface methodology. [ABSTRACT FROM AUTHOR]

The prevalence of various kidney diseases has become a significant threat to global public health and one of the leading causes of severe morbidity and high mortality. Multiple extrinsic or intrinsic factors, including drug or chemotoxicity, aging biomarkers, and various aging-related disorders, may exacerbate multiple kidney diseases and subsequently lead to end-stage renal disease (ESRD). In addition, the complications of kidney pathologies further pose challenges to current clinical practices. However, amid the development of various novel therapeutic approaches against kidney diseases, the interest in natural products or nutraceutical-based treatments has been growing and active in research on renal disorders. Amongst these, luteolin-a flavone, has been shown to be potent in combatting kidney disorders by effectively preventing and ameliorating the progression of various kidney biomarkers and associated pathologies. Therefore, this systemic review assimilates the evidence of numerous in-vitro and in-vivo studies along with the progress in luteolin-based drug development to enlighten its pharmacological potency in treating kidney disorders. The existing reports strongly support the promising therapeutic benefits of luteolin and thus, the review suggests conducting clinical studies to establish it as a potent therapeutic agent against kidney diseases. [ABSTRACT FROM AUTHOR]

A total of 43 compounds, including phenolic acids, flavonoids, lignans, and diterpene, were identified and characterized using UPLC‐ESI‐Q‐TOF‐MS coupled with UNIFI software. The identified flavonoids were mostly isomers of luteolin, apigenin, and quercetin, which were elucidated and distinguished for the first time in pepper cultivars. The use of multivariate data analytics for sample discrimination revealed that luteolin derivatives played the most important role in differentiating pepper cultivars. The content of phenolic acids and flavonoids in immature green peppers was generally higher than that of mature red peppers. The pepper extracts possessed significant antioxidant activities, and the antioxidant activities correlated well with phenolic contents and their molecular structure. In conclusion, the findings expand our understanding of the phytochemical components of the Chinese pepper genotype at two maturity stages. Moreover, a UPLC‐ESI‐Q‐TOF‐MS in negative ionization mode rapid methods for characterization and isomers differentiation was described. [ABSTRACT FROM AUTHOR]

To explore the active substances and targets of Danbie Capsules in Endometriosis therapy. Methods: This study was conducted through TCMSP and published literature screened and obtained 183 active substances of Danbie Capsules, combined and intersected with Endometriosis target genes collected and screened in the GEO database, obtained 24 target genes for Endometriosis treatment, and mapped the target network map of Danbie Capsules active substances against Endometriosis. The network was analyzed with the aid of Cytoscape version 3.9.1. With the aid of the platform of the STRING data analysis, PPI network analysis was conducted on 24 anti-Endometriosis targets of the Danbie Capsules. Results: The research results obtained three critical active substances, namely, Quercetin, β-sitosterol, and Luteolin. Seven critical targets were identified, and two representative genes (TP53 and AKT1) have been verified in Macromolecular docking and immunohistochemical verification. Conclusion: The active substances of Danbie Capsules in the treatment of Endometriosis are Quercetin, β-sitosterol and Luteolin, and the main targets are TP53 and AKT1. [ABSTRACT FROM AUTHOR]

Herbal teas have attracted attention as functional beverages containing luteolin and apigenin, which exhibit antioxidant and anti-inflammatory effects. The objective of this study was to develop a sensitive online automated method to determine these flavones' contents in herbal teas using in-tube solid-phase microextraction (IT-SPME) coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS). These compounds were extracted and concentrated by IT-SPME using a Supel Q PLOT capillary column and then separated and detected within 6 min using a CAPCELL PAK C18 MG III analytical column and a negative electrospray ionization-mode multiple-reaction monitoring system by LC–MS/MS. The detection limits (S/N = 3) for luteolin and apigenin were 0.4 and 0.8 pg mL−1, respectively, and the calibration curves were linear in the range of 2–2000 pg mL−1 with correlation coefficients above 0.9995, and intra-day and inter-day precisions with relative standard deviations below 2.9 and 3.6% (n = 6), respectively. The luteolin and apigenin in herbal tea were quantified using IT-SPME/LC-MS/MS following the acid hydrolysis of their glycosides. Among the 10 herbal teas tested, luteolin was detected in peppermint and sage at concentrations of 375 and 99 µg mL−1, respectively, while apigenin was detected in German chamomile at 110 µg mL−1, which were higher than in the other herbal teas. The method is expected to be a useful method for evaluating the efficacy of luteolin and apigenin in herbal teas as functional beverages. [ABSTRACT FROM AUTHOR]

Luteolin is an important secondary metabolite of maize, which can be glycosylated through uridine diphosphate glycosyltransferase (UGT). Extensive research on UGT has been centered in Arabidopsis thaliana, but little in maize. We cloned two maize glycosyltransferase genes, ZmUGT84A3 and ZmUGT84A4. In vitro experiments revealed that ZmUGT84A3 and ZmUGT84A4 glycosylated luteolin to both luteolin-7-O-glucoside and luteolin-4′,7-di-O-glucoside. Notably, both ZmUGT84A3 and ZmUGT84A4 catalyzed glycosylation of many flavonoids including apigenin, naringenin, eriodyctiol, kaempferol, and quercetin. Increased temperature enhanced activities of both ZmUGT84A3 and ZmUGT84A4, and elevated a production of luteolin-4′,7-di-O-glucoside. ZmUGT84A3 activity was optimal under acidic conditions but ZmUGT84A4 preferred alkaline environments. ZmUGT84A4 exhibited higher catalytic activities (1.3 to 2.6-fold) at various substrate concentrations than did ZmUGT84A3; the latter enzyme evidenced a unique activity pattern. Enzyme-catalyzed reaction processes of ZmUGT84A3 and ZmUGT84A4 in vitro for luteolin were depicted. This study unveiled two novel multifunctional glycosyltransferases identified in maize, which exhibited extensive substrate specificity, possessed multiple catalytic sites, and offered valuable insights for studying their enzymatic characteristics. [ABSTRACT FROM AUTHOR]

Lonicera japonica Thunb. is widely used in Asian countries as a food ingredient to make healthy drinks, with lonicerin, a flavone O-glycoside, as a predominant bioactive compound. This study investigated lonicerin’s effects on high-fat diet-induced hepatic steatosis in mice, compared to its aglycone luteolin. Results showed that lonicerin significantly reduced diet-induced body weight gain and hepatic lipid accumulation in mice, demonstrating greater efficacy than luteolin. This lipid-lowering effect was due to inhibited hepatic fatty acid (FA) biosynthesis and promoted fecal lipid excretion. Moreover, lonicerin favorably modulated gut microbiota by increasing Dubosiella, Eubacterium_brachy_group, and Bilophila, while reducing the pathogenic Desulfovibrionaceae. These changes led to elevated short-chain fatty acid production and altered fecal bile acid (BA) profiles, likely activating the intestinal FXR-FGF15 pathway to inhibit hepatic FA synthesis. In conclusion, lonicerin alleviated diet-induced hepatic steatosis by promoting fecal lipid excretion and inhibiting hepatic FA biosynthesis through modulating the gut microbiota-BA-intestinal FXR axis.

ABSRTACT: Resistance of Escherichia coli (E.coli) to antibiotics has steadily increased over time; hence, there is an urgent need to develop safer alternatives to antibiotics. The present study aimed to evaluate the effect of luteolin (Lut) on E. coli from chicken. The bioactive compound Lut from Humulus scandens was selected by network pharmacology and molecular docking analyses. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal laser scanning microscopy (CLSM) were used to observe the effects of Lut on the morphology and structure of E. coli cells. The data-independent acquisition (DIA) method was used to analyze protein expression level of E. coli before and after Lut treatment. The in vivo evaluation of the antibacterial, anti-inflammatory, and oxidative effects of Lut on E.coli was conducted using E.coli isolated strains infected the SPF chicken model. The network pharmacology analysis revealed 19 distinctive bioactive compounds such as Lut and β-sitosterol in H. scandens; furthermore, 30 core targets were selected from H. scandens. The KEGG enrichment analysis showed that the PI3K-Akt, TNF, MAPK, IL-17, JAK-STAT, and HIF-1 pathways were related from H. scandens. Based on the results of the network pharmacology analysis, Lut was subjected to screening by molecular docking analysis to determine its antibacterial effect on E. coli and the associated mechanism of action. The minimum inhibitory concentration (MIC) of Lut against E. coli standard strains was 500 µg/mL. SEM, TEM, and CLSM results indicated that Lut damaged the cell wall and cell membrane of E. coli strains and destroyed the cell structure, leading to cell death.The expression level of membrane structure, Phenylalanine metabolism and some other metabolic pathways in E.coli changed after treatment with Lut (P < 0.05). In vivo experiments in the SPF chicken model showed that Lut treatment alleviated the decline in the growth performance of chickens (P < 0.05), prevented pathological changes in the correspond ding organs and suppressed the inflammatory response induced by E. coli infection (P < 0.05), improved the immunity and antioxidant capacity of chickens (P < 0.05), and protected them against infection with E. coli strains. To summarize, Lut from H. scandens can inhibit E. coli growth by damaging the cell membrane structureand affecting the expression level of some metabolic proteins. In vivo experiments also showed that Lut can significantly reduce the damage caused by E. coli isolates on SPF chickens, improve their antioxidant capacity and immunity, and reduce inflammatory responses following E. coli infection.

ABSTRACT: Environmental pollution poses a significant challenge to the poultry industry, leading to substantial losses and adverse effects on the health, production, and performance of avian species. In recent years, there has been growing interest in exploring natural compounds with potential protective effects against cadmium (Cd)-induced toxicity. Luteolin (LUT), a flavonoid found in various plants, has been studied for its antioxidant, anti-inflammatory, and cytoprotective properties. In this study, Su green shell grass chickens were divided into 4 groups: control, LUT (150 mg LUT), Cd (100 mg CdCl2), and Cd + LUT (100 mg CdCl2 + 150 mg LUT) groups for 1 month, respectively. The present study revealed that LUT maintained the morphology and functional activity of the liver and intestine. LUT alleviated Cd-induced impairment in the liver and intestinal biochemical indicators, suppressed Cd-induced liver fibrosis, mitigated liver and intestinal tissue damage. Additionally, LUT reduced oxidative stress and regulated the Cd-induced impairment in trace elements of the liver and intestine. Furthermore, LUT reduced Cd-induced liver inflammation, restored Cd-induced intestinal barrier function, and normalized Cd-induced serum proteins, including changes in the content of glutamyltranspeptidase. Moreover, LUT maintained Cd-induced disruption of gut microbiota and alleviated bacterial dysbiosis. Overall, these findings suggest that LUT holds promise as a potential therapeutic agent for mitigating the adverse effects of Cd-induced toxicity in poultry, by preserving liver and intestinal health, reducing oxidative stress, inflammation, and restoring gut microbiota balance.

Aromatase is an enzyme that converts androgens (like testosterone) to estrogens (like 17- estradiol). It is also a highly successful therapeutic target for endocrine-responsive breast cancer. Aromatase inhibitors, which suppress estrogen synthesis in postmenopausal women, have been useful in the treatment of individuals with estrogen receptor-positive breast cancer. Anastrozole is an aromatase inhibitor medication that is used in the management and treatment of breast cancer. Flavonoids inhibit cancer cell proliferation by causing apoptosis, encouraging autophagy, and changing the cell cycle. Although several dietary flavonoids (like in parsley, celery and Broccoli) can inhibit aromatase, the tissue specificity and mechanism of binding are uncertain. According to several researches, flavonoids (apigenin and luteolin) dramatically suppress estrogen production. The study aims to examine binding of 3EQM (Aromatase) in the A chain with both of flavonoid (Apigenin and luteolin) and Anastrozole, using an in silico approach. PyRx default program was used to detect docking accuracy. Virtually, results showed that flavonoids have higher binding strength for apigenin and luteolin (which was -8.2 and -8.3) than Anastrozole (which was -7.6) with chain A of Aromatase. So, flavonoids can potentially be used as a natural medication to reduce breast cancer incidence. However, clinical trial studies are needed to investigate the role of apigenin and luteolin in the treatment of breast cancer.

Abstract 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.

Combining two or more chemicals in chemotherapy is rapidly increasing because of its higher efficacy, lower toxicity, lower dosages, and lower drug resistance. Here, we identified a novel combination of luteolin (LUT) and curcumin (CUR), two bioactive compounds from foods, synergistically suppressed triple-negative breast cancer (TNBC) cell proliferation (LUT 30 µM + CUR 20 µM), colony formation (LUT 1 µM + CUR 2 µM), and tumor growth in xenograft mice (LUT 10 mg/kg body weight/day + CUR 20 mg/kg body weight/day, i.p. injection every other day, 5 weeks), while the individual chemical alone did not show these inhibitory effects significantly at the selected concentrations/dosages. Our total RNA transcriptome analysis in xenograft tumors revealed that combining LUT and CUR synergistically activated type I interferon (IFN) signaling and suppressed transforming growth factor-beta (TGF-β) signaling pathways, which was further confirmed by the expression/activity of several proteins of the pathways in tumors. In addition, this combination of LUT and CUR also synergistically decreased oncoprotein levels of c-Myc and Notch1, the critical molecules required to maintain stem cell properties, tumor clonal evolution, and drug resistance. These results suggest that the combination of LUT and CUR synergistically inhibits TNBC by suppressing multiple cellular mechanisms, such as proliferation, colony formation, and transformation, as well as tumor migration, invasion, and metastasis, via regulating IFN and TGF-β signaling pathways. Therefore, combining LUT and CUR may be an effective therapeutic agent to treat highly aggressive, drug-resistant TNBC patients after clinical trials.

In infantile nephropathic cystinosis, variants of the CTNS gene cause accumulation of cystine in lysosomes, causing progressive damage to most organs. Patients usually present before 1 year of age with signs of renal Fanconi syndrome. Cysteamine therapy allows cystine clearance from lysosomes and delays kidney damage but does not prevent progression to end-stage kidney disease, suggesting that pathways unrelated to cystine accumulation are also involved. Among these, impaired autophagy, altered endolysosomal trafficking, and increased apoptosis have emerged in recent years as potential targets for new therapies. We previously showed that luteolin, a flavonoid compound, improves these abnormal pathways in cystinotic cells and in zebrafish models of the disease. Herein, we have investigated if prolonged luteolin treatment ameliorates kidney damage in a murine model of cystinosis. To this end, we have treated Ctns-/- mice from 2 to 8 months with 150 mg/kg/day of luteolin. No significant side effects were observed. Compared to untreated animals, analyses of kidney cortex samples obtained after sacrifice showed that luteolin decreased p62/SQSTM1 levels (p

Introduction: Traditional Chinese Medicine (TCM) is renowned for its holistic treatment approach and minimal side effects. Luteolin (LUT) and Quercetin (QUE) each possess notable anticancer properties. This study is the first to elucidate the synergistic anticancer activity of the combination of LUT and QUE (LUT+QUE) against lung cancer. Methods: The synergistic anticancer activity of QUE+LUT was evaluated through the combination index (CI) value by varying the concentrations of QUE and LUT. Network pharmacology analysis was then employed to identify the key targets and crucial signaling pathways for QUE and LUT. Finally, the synergistic anticancer mechanisms of QUE+LUT were elucidated by verifying these core targets and pathways through various experiments, including apoptosis assays, migration assays, ELISA, Western blot and reactive oxygen species (ROS) assays. Results: The key targets identify through network pharmacology analysis include BCL2L1, MMP9, JUN, PTGS2, TP53, AKT1 and CASP3. The crucial pathways are the PI3K-Akt signaling pathway and chemically-induce carcinogenic ROS pathways. Cellular experiments demonstrate that QUE+LUT synergistically induce apoptosis, inhibit cell proliferation, migration and invasion, increase ROS levels and regulate the PI3K-Akt signaling pathway, effectively targeting lung cancer cells. Discussion: The combined therapy of QUE and LUT holds potential as an effective treatment for cancer patients, providing valuable insights for the selection and mechanistic exploration of important anticancer drugs.

Abstract Background Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. Methods Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. Results Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. Conclusion Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

Objective(s): Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury.Materials and Methods: Luteolin and 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (20 μmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation.Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

Zhe Yu,1– 3 Ruoqi Ding,1– 3 Qiuju Yan,1– 3 Menghan Cheng,1– 3 Teng Li,1– 4 Fei Zheng,5 Lin Zhu,1– 4 Yang Wang,1– 4 Tao Tang,1– 4 En Hu1– 4 1Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 4Xiangya Hospital, Central South University, Nanchang, Jiangxi, 330004, People’s Republic of China; 5The College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410008, People’s Republic of ChinaCorrespondence: En Hu; Ruoqi Ding, Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China, Email znxyhe@csu.edu.cn; ruoqi_ding@outlook.comPurpose: Many herbs can promote neurological recovery following traumatic brain injury (TBI). There must lie a shared mechanism behind the common effectiveness. We aimed to explore the key therapeutic targets for TBI based on the common effectiveness of the medicinal plants.Material and methods: The TBI-effective herbs were retrieved from the literature as imputes of network pharmacology. Then, the active ingredients in at least two herbs were screened out as common components. The hub targets of all active compounds were identified through Cytohubba. Next, AutoDock vina was used to rank the common compound-hub target interactions by molecular docking. A highly scored compound-target pair was selected for in vivo validation.Results: We enrolled sixteen TBI-effective medicinal herbs and screened out twenty-one common compounds, such as luteolin. Ten hub targets were recognized according to the topology of the protein-protein interaction network of targets, including epidermal growth factor receptor (EGFR). Molecular docking analysis suggested that luteolin could bind strongly to the active pocket of EGFR. Administration of luteolin or the selective EGFR inhibitor AZD3759 to TBI mice promoted the recovery of body weight and neurological function, reduced astrocyte activation and EGFR expression, decreased chondroitin sulfate proteoglycans deposition, and upregulated GAP43 levels in the cortex. The effects were similar to those when treated with the selective EGFR inhibitor.Conclusion: The common effectiveness-based, common target screening strategy suggests that inhibition of EGFR can be an effective therapy for TBI. This strategy can be applied to discover core targets and therapeutic compounds in other diseases.Keywords: traditional Chinese medicine, medicinal plants, luteolin, AZD3759, epidermal growth factor receptor, astrocyte

Abstract Neurodegenerative diseases, characterized by progressive neuronal dysfunction and loss, pose significant health challenges. Glutamate accumulation contributes to neuronal cell death in diseases such as Alzheimer's disease. This study investigates the neuroprotective potential of Albizia lebbeck leaf extract and its major constituent, luteolin, against glutamate-induced hippocampal neuronal cell death. Glutamate-treated HT-22 cells exhibited reduced viability, altered morphology, increased ROS, and apoptosis, which were attenuated by pre-treatment with A. lebbeck extract and luteolin. Luteolin also restored mitochondrial function, decreased mitochondrial superoxide, and preserved mitochondrial morphology. Notably, we first found that luteolin inhibited the excessive process of mitophagy via the inactivation of BNIP3L/NIX and inhibited lysosomal activity. Our study suggests that glutamate-induced autophagy-mediated cell death is attenuated by luteolin via activation of mTORC1. These findings highlight the potential of A. lebbeck as a neuroprotective agent, with luteolin inhibiting glutamate-induced neurotoxicity by regulating autophagy and mitochondrial dynamics.

Abstract Background HBV infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism. Methods Analysis and screening of effective antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant antiviral activity. The mechanism of antiviral action of Lut was also found by real-time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20 days. And their antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg. Results In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-β production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice. Conclusion Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B.

Luteolin is a flavonoid that occurs naturally in various fruits and vegetables. It has been shown that this compound possesses anti-inflammatory and antioxidant properties, which can significantly inhibit pathogenesis. A substantial amount of research has been performed to execute this compound’s role as an anticancer agent. Moreover, luteolin has the ability to block cell proliferation, inflammation, angiogenesis, and other cell signaling molecules that can contribute to cancer growth. This review aims to shed light on the efforts to present potential targets for luteolin in different cancers. Moreover, this review also explores the synergistic potential of this compound with other anticancer drugs. Despite its promising health-promoting benefits, it is essential to note that further research is needed based on safety, mechanism of action, efficacy, and clinical trials to reconnoiter its potential benefits in cancer management.

Acetamiprid is a class of neuroactive insecticides widely used to control insect pests. The current study aimed to investigate the potential neuroprotective effects of luteolin against acetamiprid-induced neurotoxicity in the rat cerebral cortex. Four equal groups of adult male rats (10 in each): control, acetamiprid (40 mg/kg for 28 days), luteolin (50 mg/kg for 28 days), and acetamiprid+luteolin cotreatment were used. Acetamiprid was shown to alter the oxidative state by increasing oxidant levels [nitric oxide (NO) and malondialdehyde (MDA)] and decreasing antioxidants [glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase-(CAT)], with increased activity of nuclear factor erythroid 2-related factor 2-(Nrf2). Likewise, acetamiprid increases the inflammatory response, as evidenced by increased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B-(NF-κB). In contrast, the treatment with luteolin brought these markers back to levels close to normal, showing that it protects neurocytes from oxidative damage and the neuroinflammation effects of acetamipridinduced inflammation. Luteolin also demonstrated a neuroprotective role via the modulation of acetylcholinesterase (AChE) activity in the cerebral cortex tissue. Histopathology showed severe neurodegenerative changes, and apoptotic cells were seen in the acetamiprid-induced cerebral cortex layer, which was evident by increased protein expression levels of Bax and caspase-3 and decreased Bcl-2 levels. Histochemistry confirmed the neuronal degeneration, as proven by the change in neurocyte colour from brown to black when stained with a silver stain. Luteolin may have a neuroprotective effect against biochemical and histopathological changes induced by acetamiprid in the rat cerebral cortex. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is currently one of the main threats to animal health, and flavonoids in forage have good antioxidant activity. However, the impact of fermentation on flavonoids and their antioxidant activity in forage is still unclear. This study aims to investigate the effect of lactic acid bacteria inoculation on the biological transformation of flavonoids in alfalfa silage fermentation and its relationship with antioxidant activity. Results: Compared with the raw materials, silage fermentation can increase the total flavonoid content of alfalfa. The addition of Pediococcus pentosaceus (CP115739.1) and Lactiplantibacillus plantarum (CP115741.1) can significantly increase the total flavonoid content in alfalfa silage (P < 0.05). The addition of lactic acid bacteria significantly improved the antioxidant capacity of alfalfa silage (P < 0.05). Pearson correlation analysis showed a significant correlation between total flavonoids and DPPH (R = 0.62, P < 0.05), and a highly significant correlation between total flavonoids and FRAP (R = 0.70, P < 0.01). Compared with natural silage fermentation, the addition of lactic acid bacteria leads to changes in the biological transformation process of flavonoids in alfalfa. Its unique products, 3,7,4′-trioxyflavonoids, as well as acacetin and taxifolin 7-O-rhamnoside, are significantly positively correlated with antioxidant activity. Conclusions: Silage fermentation contributes to the transformation of flavonoids, and inoculation with certain lactic acid bacteria can increase the content of flavonoids (including apigenin, luteolin, and other free flavonoids). It is worth noting that after fermentation, the antioxidant capacity of alfalfa is significantly improved, which may be attributed to the biotransformation of flavonoids related to acacetin, 3,7,4′-trihydroxyflavonoids, and taxifolin 7-O-rhamnoside. This study provides a potential pathway for obtaining value-added silage fermentation products by selecting specific lactic acid bacteria inoculants. [ABSTRACT FROM AUTHOR]

The Stachys L. genus has been widely used in traditional medicine in many countries throughout the world. The study aimed to investigate the chemical composition and bioactivity of the hydroethanolic extract (50% v/v) obtained by ultrasonication from the aerial flowering parts of Stachys sylvatica L. (SSE) collected in Almaty region (Southern Kazakhstan). According to RP-HPLC/PDA analysis the leading metabolites of the SSE belonged to polyphenols: chlorogenic acid and its isomers (2.34 mg/g dry extract) and luteolin derivatives (1.49 mg/g dry extract), while HPLC-ESI-QTOF-MS/MS-based qualitative fingerprinting revealed the presence of 17 metabolites, mainly chlorogenic acid and its isomers, flavonoid glycosides, and verbascoside with its derivatives. GC-MS analysis of the volatile metabolites showed mainly the presence of diterpenoids and fatty acid esters. A reduction in the viability of nematodes Rhabditis sp. was obtained for the SSE concentration of 3.3 mg/mL, while 11.1 mg/mL showed activity comparable to albendazole. The SSE exhibited higher activity against Gram-positive (MIC = 0.5-2 mg/mL) than Gram-negative bacteria and yeast (MIC = 8 mg/mL), exerting bactericidal and fungicidal effects but with no sporicidal activity. The SSE showed some antiviral activity against HCoV-229E replicating in MRC-5 and good protection against the cytopathic effect induced by HHV-1 in VERO. The SSE was moderately cytotoxic towards human cervical adenocarcinoma (H1HeLa) cells (CC50 of 0.127 mg/mL after 72 h). This study provides novel information on the SSE extract composition and its biological activity, especially in the context of the SSE as a promising candidate for further antiparasitic studies. [ABSTRACT FROM AUTHOR]

Single-cell nanoencapsulation (SCNE) has great potential in the enhancement of therapeutic effects of probiotic microbes. However, the material scope has been limited to water-soluble compounds to avoid non-biocompatible organic solvents that are harmful to living cells. In this work, the SCNE of probiotic Lactobacillus acidophilus with water-insoluble luteolin and Fe3+ ions is achieved by the vortex-assisted, biphasic water–oil system. The process creates L. acidophilus nanoencapsulated in the luteolin-Fe3+ shells that empower the cells with extrinsic properties, such as resistance to lysozyme attack, anti-ROS ability, and α-amylase-inhibition activity, as well as sustaining viability under acidic conditions. The proposed protocol, embracing water-insoluble flavonoids as shell components in SCNE, will be an advanced add-on to the chemical toolbox for the manipulation of living cells at the single-cell level. [ABSTRACT FROM AUTHOR]

Obesity is characterized by excessive body fat accumulation and is a high-risk factor for metabolic comorbidities, including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. In lean individuals, adipose tissue (AT) is not only an important regulatory organ for energy storage and metabolism, but also an indispensable immune and endocrine organ. The sustained energy imbalance induces adipocyte hypotrophy and hyperplasia as well as AT remodeling, accompanied by chronic low-grade inflammation and adipocytes dysfunction in AT, ultimately leading to systemic insulin resistance and ectopic lipid deposition. Luteolin is a natural flavonoid widely distributed in fruits and vegetables and possesses multifold biological activities, such as antioxidant, anticancer, and anti-inflammatory activities. Diet supplementation of this flavonoid has been reported to inhibit AT lipogenesis and inflammation as well as the ectopic lipid deposition, increase AT thermogenesis and systemic energy expenditure, and finally improve obesity and associated metabolic diseases. The purpose of this review is to reveal the nutritional activities of luteolin in obesity and its complications with emphasis on its action on AT energy metabolism, immunoregulation, and endocrine intervention. [ABSTRACT FROM AUTHOR]

Background: Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. Methods: Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. Results: Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. Conclusion: Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury. [ABSTRACT FROM AUTHOR]

Phytochemicals are chemical compounds derived from therapeutic plants that have a variety of pharmacological effects. In particular, flavonoids are the most effective phytochemical components with various biological activities and pharmacological effects. Luteolin is an important flavonoid found naturally in many plant species. This study aimed to investigate the antibacterial effect of luteolin flavonoid obtained from terebinth (Pistacia terebinthus L.) bark extracts. In the study, MIC values of luteolin against reference strains Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Streptococcus agalactiae ATCC 12401, Enterococcus feacalis ATCC 29212 were investigated by broth microdilution method. As a result of the study, it was determined that luteolin showed antibacterial activity against all tested strains. [ABSTRACT FROM AUTHOR]

The article aimed to investigate the main chemical components and their mechanism of action of Gong Xian Zhi Li San for the treatment of piglet diarrhea based on network pharmacology. The effective components and pathways of Gong Xian Zhi Li San were determined by databases (TCMSP, Herb, OMIM, BIOGPS, etc.). The results showed that a total of 49 active components were collected, including three Mahonia fortunei (Lindl.) Fedde, four Ilex rotunda Thunb, 24 Sophora flavescens Aiton, six Geranium wilfordii Maxim, and 12 Acalypha australis L.. According to Degree value, the top five components were quercetin, kaempferol, luteolin, β -sitosterol, and palmatine. There were 262 corresponding targets, and the key targets were RELA, MAPK3, MAPK1, HSP90AA1, TNF, and so on. There were 4 012 GO entries, 206 CC entries, 3 459 BP entries, and 347 MF entries by GO enrichment analysis. The KEGG pathway was enriched with 230 signal pathways, and the targets were mainly acting on the AGE-RAGE, IL-17, and TNF signaling pathways. The study indicates that Gong Xian Zhi Li San improve piglet diarrhea by the regulating AGE-RAGE signal pathway, IL-17 signal pathway, and TNF signal pathway through the action of quercetin, kaempferol, luteolin, β-sitosterol, and palmatine on RELA, MAPK3, MAPK1, HSP90AA1, and TNF. [ABSTRACT FROM AUTHOR]