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Hepatocellular carcinoma (HCC) is a primary malignant neoplasm exhibiting a high mortality rate. Taxifolin is a naturally occurring flavonoid compound that exhibits a range of pharmacological properties. The effects of taxifolin on HCC remain largely unexplored. Therefore, the aim of this study was to examine the potential roles of taxifolin in the development and progression of HCC. In this study, CCK-8 assay was utilized to examine the impact of taxifolin on the cell viability. The copper ions level and the activity of mitochondrial respiratory chain were determined by the correspondent kits. The biological properties of HCC cells were evaluated using colony formation, transwell, flow cytometry, and TUNEL assays, respectively. Transcriptome sequencing was carried out either with or without taxifolin treatment. The expression of cuproptosis-related proteins was determined by Western blot. We observed significant decrease of cell viability, Glutathione (GSH), and mitochondrial respiratory chain under the treatment of taxifolin, while an increase of copper ions level. Taxifolin was observed to suppress HCC progression both in vitro and in vivo. The intersection analysis was performed between upregulated genes and cuproptosis-related genes to obtain one intersection gene-SLC31A1. The knockdown of SLC31A1 reversed the tumor-suppressive effects induced by taxifolin. Taxifolin inhibited HCC progression through inducing cuproptosis in an SLC31A1-mediated manner. [ABSTRACT FROM AUTHOR]

This study investigates the effect of taxifolin and arabinogalactan premixed with dihydroquercetin (Lavitol V) at different concentrations on the quality changes of trout soup at 4 ± 1°C for 31 days. Shelf life studies included physiochemical, sensory, and microbiological quality measures. The shelf lives of the fish soups were extended for 2–4 and 7–10 days with taxifolin and Lavitol V, respectively, with significant variations (p < 0.05), the longest shelf life corresponding to Lavitol V for 31 days. The highest TBA and TVB-N were obtained for the control as 3.72 mg MA/kg and 11.21 mg/100 g, respectively. Therefore, Lavitol V has a good potential for future applications in seafood preservation. [ABSTRACT FROM AUTHOR]

Taxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased "beneficial" microbes such as Intestinimonas , Coprococcus , Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the "harmful" intestinal bacteria such as Prevotella , Howardella , Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance. [ABSTRACT FROM AUTHOR]

Background/Objectives: The current approach to obesity care, which primarily focuses on weight loss, is often insufficient because of the challenges in maintaining long-term results. Therefore, novel, safe, and sustainable medications for obesity are highly anticipated. Taxifolin, a natural bioactive flavonoid, was found to exert pleiotropic protective effects against various diseases. Our experimental in vivo and in vitro studies revealed that taxifolin administration contributes to weight loss. Accordingly, we hypothesized that long-term oral intake of taxifolin was clinically associated with weight loss. Methods: A retrospective longitudinal study was conducted on participants who consistently monitored their body weight during routine clinic visits between January 2021 and July 2021. Body weight changes of the patients who received 300 mg/day of taxifolin were compared with those of patients who did not receive taxifolin. Results: The study enrolled a total of 62 patients: 36 received taxifolin and 26 did not receive taxifolin. Long-term intake of taxifolin showed greater weight loss than those not receiving taxifolin over a mean follow-up of 176.1 and 177.7 days, respectively (−1.6 vs. −0.3 kg; p = 0.026). Furthermore, long-term taxifolin intake was an independent predictor of increased weight loss (adjusted β [mean difference] −0.14, 95% confidence interval [−2.69, −0.18], p = 0.026). No adverse events were observed. Conclusions: Long-term daily oral intake of taxifolin may safely and sustainably prevent or manage obesity. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the predominant causes of mortality in women worldwide. Although therapeutics such as surgery, chemotherapy, hormonal therapy, and radiotherapy have been used, they are associated with adverse effects or multidrug resistance. The use of natural compounds is a promising strategy, owing to their abundance and medicinal value. This review focuses on six natural compounds, namely cinnamaldehyde, diosmin, taxifolin, phloretin, arctigenin, and eugenol, and details their mechanisms of breast cancer inhibition based on in vitro and in vivo studies. These compounds generally promote apoptosis and cell cycle arrest, hinder metastasis and invasion, and decrease tumor growth. This review reinforces the use of natural compounds as therapeutics for breast cancer from their preclinical studies. These compounds might be promising for drug development due to their abundance, high reliability, and safety. [ABSTRACT FROM AUTHOR]

Chunli Qi,1– 3,&ast; Huijie Xing,2,3,&ast; Ning Ding,4 Weifeng Feng,5 Yongyi Wu,6 Xingwang Zhang,7 Yigang Yu1 1School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, People’s Republic of China; 2Institute of Laboratory Animals, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou, 510632, People’s Republic of China; 4Department of Animal, Plant and Food, Guangzhou Customs Technology Center, Guangzhou, 510623, People’s Republic of China; 5Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 6Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 7Department of Pharmaceutics, School of Pharmacy, Jinan University, Guangzhou, 511443, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingwang Zhang, Email zhangxw@jnu.edu.cn; Yigang Yu, Email yuyigang@scut.edu.cnPurpose: Diabetes mellitus (DM) remains a significant health challenge, with traditional treatments often failing to provide lasting solutions. Taxifolin (Tax), a potential phytomedicine with antioxidant and anti-hyperglycemic properties, suffers from low water solubility and poor bioavailability, necessitating advanced delivery systems. This study aims to nanometerize taxifolin (Tax) into selenized liposomes (Tax-Se@LPs) for enhanced oral delivery and hypoglycemic effect.Methods: Tax-Se@LPs were fabricated through a thin-film hydration/in situ reduction technique. The resulting nanomedicine was characterized through in vitro release studies, pharmacokinetic and pharmacodynamic evaluations, cellular uptake assays, and formulation stability tests.Results: The optimized Tax-Se@LPs demonstrated an average particle size of 185.3 nm and an entrapment efficiency of 95.25% after optimization. In vitro release studies revealed that Tax-Se@LPs exhibited a slower and more sustained release profile compared to conventional liposomes, favoring gastrointestinal drug absorption. Pharmacokinetic evaluations in normal rats indicated that Tax-Se@LPs achieved a relative bioavailability of 216.65%, significantly higher than Tax suspensions and unmodified liposomes. Furthermore, in diabetic GK rats, Tax-Se@LPs resulted in a maximal blood glucose reduction of 46.8% and exhibited a more sustained therapeutic duration compared to other formulations. Cellular uptake tests manifested that selenization altered the internalization mechanisms of liposomes while preserving their absorption aptness by intestinal epithelial cells. The physiological and in vitro stability of Tax-Se@LPs was also reinforced by selenization.Conclusion: Overall, Tax-Se@LPs not only improve the oral bioavailability of Tax but also enhance its therapeutic efficacy. These findings underscore the potential of Tax-Se@LPs as a promising therapeutic strategy for DM management.Keywords: taxifolin, liposomes, selenium, diabetes mellitus, bioavailability, hypoglycemic effect

This review is a detailed analysis of the results of the experimental studies carried out by scientists from different countries and devoted to the practical application of dihydroquercetin in food products. The main attention is paid to the antioxidant and functional properties of the bioflavonoid in the composition of milk and dairy products. Currently, dihydroquercetin is considered the most powerful natural antioxidant, which use prolongs the shelf-life of products and has a beneficial effect on the human body. Although much time has passed since dihydroquercetin discovery by Russian scientists, today a significant part of research of the bioflavonoid is focused on the pharmaceutical sphere, while its use in the food industry is at the initial stage of the development. In the article, studies carried out by Russian, Chinese, Japanese, European, American and other foreign authors are systemized, which allowed describing quite thoroughly trends in the use of dihydroquercetin in the global industry. Having focused on the influence of the antioxidant on the characteristics of dairy products, scientists found that it increases the stability of acidity and pH, inhibits the development of the pathogenic microflora, favorably affects taste and aroma. Prospect directions for its use have been revealed, and directions for further research of the use of this antioxidant in the dairy industry have been identified. It is concluded that the addition of dihydroquercetin into a recipe will allow obtaining new functional (parapharmaceutical) food products with the antioxidant stability to prevent socially significant diseases and improve the health of the population.

Dihydroquercetin (DHQ, taxifolin) is a plant flavonoid that exhibits antioxidant and cytoprotective properties in animal and human cells. Its effect on programmed cell death (PCD), respiration, photosynthesis, and the formation of reactive oxygen species (ROS) in plant cells has been shown. At concentrations of 0.1–3 mM, DHQ suppressed KCN-induced PCD in guard cells of pea leaf epidermis in the light or in the dark, which was determined by the destruction of cell nuclei. In pea leaf cuttings, DHQ had no effect on respiration, as measured by O2 consumption in the dark. DHQ did not affect photosynthetic O2 evolution by leaf cuttings with p-benzoquinone and ferricyanide as electron acceptors nor on the consumption of oxygen as a result of the oxidation of ascorbate and N,N,N′,N′-tetramethyl-p-phenylenediamine and the reduction of methyl viologen in the light in PS I. DHQ inhibited menadione-induced ROS formation in pea leaf epidermis, which was detected by fluorescence 2′,7′-dichlorofluorescein. DHQ itself had no effect on H2O2 in solution, but it utilized hydrogen peroxide in combination with peroxidase. The antioxidant effect of DHQ and protection of plant cells from death may be due to its suitability as a peroxidase substrate. [ABSTRACT FROM AUTHOR]

The interaction of two structurally similar flavonoids, isorhamnetin or taxifolin with human serum albumin (HSA) were investigated by fluorescence spectroscopy, CD spectroscopy and computer simulation techniques. Their binding properties, binding sites, binding modes and the effects on the conformation of HSA were determined. The fluorescence spectra showed that isorhamnetin or taxifolin formed a stable complex with HSA, and binding constants reached 105 L mol-1, hydrogen bonds and hydrophobic force were the main binding forces. The sites competition experiments and molecular docking showed that the site I of subdomain IIA in HSA was the main binding site of isorhamnetin or taxifolin. Synchronous fluorescence, CD spectra, surface hydrophobicity experiments and molecular dynamics simulations indicated that the binding of isorhamnetin or taxifolin induced the conformational changes of HSA, and the polypeptide skeleton was partially extended. [ABSTRACT FROM AUTHOR]

Clozapine is an atypical antipsychotic (AAP) drug used in treatment-resistant schizophrenia patients. The adverse effects of clozapine on the heart may result in death and require drug discontinuation. Inflammatory mechanisms are thought to be responsible for the negative effect of clozapine on the heart. This suggests that using an agent with anti-inflammatory and antioxidant properties, which may be specific to clozapine-induced heart damage, may prevent possible damage. The aim of our study is to evaluate the effect of taxifolin (3 , 5 , 7 , 3 ', 4'-pentahydroxy flavanone), an agent with known antioxidant and anti-inflammatory effects, on myocardial damage caused by clozapine with biochemical and histopathological data. The rats were divided into three equal groups: healthy control group (HC), clozapine-treated group (CLN), and taxifolin + clozapine-treated group (TCL). To perform this experiment, taxifolin was administered to TCL (n-6) rats at a dose of 50 mg/kg orally by gavage into the stomach. In the HC (n-6) and CLN (n-6) groups, the same volume of distilled water was administered orally as a solvent. One hour after the administration of taxifolin and distilled water, clozapine was administered orally at a dose of 20 mg/kg to the TCL and CLN groups once a day for 28 days. At the end of the period, troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in the venous blood of each group. Malondialdehyde (MDA), total glutathione (tGSH), TNF-α, NF-▪B, and IL-1β levels were measured in samples taken from heart tissues. Additionally, heart tissues were evaluated histopathologically. Troponin I, CK-MB, MDA, TNF-α, NF-▪B, and IL-1β levels, myocardial degeneration, myofiber irregularity, and congestion scores were significantly higher and tGSH levels were lower in the clozapine group than in the healthy control and taxifolin + clozapine groups (P < 0.05). Compared with the healthy control group, troponin I, tGSH, and NF-KB levels were similar (P > 0.05), CK-MB, MDA, TNF-α, and IL-1β levels were higher in the taxifolin + clozapine group, while they were significantly lower than the clozapine group (P < 0.05). Histopathologically evaluated myocardial degeneration, myofiber irregularity, and congestion score were significantly lower in the taxifolin + clozapine group than in the clozapine group. In the clozapine group (CLN group), myofibers were found to have irregular patterns and were observed as irregular. In the taxifolin + clozapine group (TLC group), myofibrils generally showed a regular morphology. We found that taxifolin can ameliorate damage to myocardial tissue by regulating oxidant-antioxidant and proinflammatory cytokine levels. The data of our study suggest that taxifolin may be useful in the treatment of clozapine-induced myocardial injury. [ABSTRACT FROM AUTHOR]

AbstractBy establishing an in vitro model of D-Gal-induced brain neuronal cell (HT-22) senescence, it was found that TAX treatment significantly increased the activities of SOD and GSH, while decreasing MDA levels in aging HT-22 cells, indicating that TAX effectively restored the total antioxidant capacity and antioxidant enzyme activity of aging HT-22 cells induced by D-Gal, and attenuated cellular oxidative stress injury. In addition, taxifolin could also protect HT-22 cells from aging by up-regulating SIRT1 while reducing the expression of Ac-p53, indicating that TAX may be an active substance that can effectively delay cell aging. [ABSTRACT FROM AUTHOR]

To preclinically study the effectiveness of new antihypertensive drugs, various animal hypertension models are used. However, most of them do not correspond to primary hypertension, which develops in people with age. We used male Wistar rats of 4, 10, 12 and 18 months old. The animals were divided according to systolic blood pressure (SBP) into normotensive (SBP ≤ 114 mmHg) or hypertensive (SBP ≥ 115 mmHg). Within hypertensive animals, two cohorts were distinguished—with SBP below and above 125 mmHg. The animals received 100 µg/kg of taxifolin intraperitoneally for 7 days. A significant difference was shown between animals with SBP above and below 115 mmHg, as well as between cohorts of hypertensive animals with SBP above and below 125 mmHg within each age. The number of animals with elevated SBP increased with age both for clusters with an SBP above 115 mmHg and for cohorts with an SBP above 125 mmHg. Administration of taxifolin led to a significant decrease in the SBP only in hypertensive animals. A physiological model of age-related hypertension was obtained in male Wistar rats. It has been shown that hypertension develops and worsens with age. In preclinical studies, it should be taken into account that drugs may have different effects depending on the initial SBP of the animals. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX)‐induced peripheral neuropathy (PIPN) is a disabling side effect of PTX, which adversely affects the life quality of cancer patients. Flavonoids such as hesperidin methyl chalcone (HMC) and taxifolin (TAX) can alleviate neuropathic pain via their anti‐inflammatory, antioxidant, neuroprotective, and antinociceptive properties. The current study aimed to assess the efficacy of HMC and TAX in preventing PIPN individually or in combination. Pretreatment with HMC and TAX mitigated PTX‐induced mechanical allodynia and hyperalgesia, cold allodynia, and thermal hyperalgesia as well as restore the normal histological architecture. Remarkably, neuropathic pain was relieved by suppression of nerve growth factor (NGF), p38 mitogen‐activated protein kinase (p38 MAPK), and transient receptor potential vanilloid type‐1 (TRPV1), which ultimately lead to reduced calcitonin gene‐related peptide (CGRP). Furthermore, both HMC or TAX enhanced nuclear factor erythroid 2–related factor 2 (Nrf2), leading to elevated glutathione (GSH) and total antioxidant capacity (TAC) along with lowered malondialdehyde (MDA), which in turn, downregulated nuclear factor kappa B P65 (NF‐κB P65) and its phosphorylated form and eventually reduced tumor necrosis factor alpha (TNF‐α) and interleukin‐1 beta (IL‐1β) then lowered the apoptotic indices. Promisingly, the combination of both agents was superior to each drug alone through targeting more diverse signaling pathways and achieving synergistic and comprehensive therapeutic effects. In conclusion, pretreatment with HMC and TAX separately or in combination alleviated PIPN via modulating NGF/p38 MAPK/NF‐κB P65/TRPV1/CGRP pathway. [ABSTRACT FROM AUTHOR]

Solid-state drug delivery systems for the drug substances transport are of great importance nowadays. In the present work, the non-covalent interactions between taxifolin (Tax) and graphene as well as nitrogenated (N-doped) graphenes were systematically studied by using a wide set of theoretical techniques. Symmetry-adapted perturbation theory (SAPT0) calculations confirmed more favorable adsorption of Tax on N-doped graphenes compared to pristine graphene. It was established that dispersion interactions play the main role in the attractive interactions (>60%), whereas electrostatic and induction forces contribute only moderately to the attraction (~25% and 7–8%, respectively). Independent gradient model (IGM) analysis visually demonstrated the existence of dispersion interactions and hydrogen bonding in the studied Tax complexes. Ab initio molecular dynamics calculations indicated stability of these complexes at different temperatures. Our results show that N-doped graphenes with the enhanced interaction energy (Eint) toward Tax are promising candidates for the technical realization of the targeted drug delivery systems.

Solid-state drug delivery systems for the drug substances transport are of great importance nowadays. In the present work, the non-covalent interactions between taxifolin (Tax) and graphene as well as nitrogenated (N-doped) graphenes were systematically studied by using a wide set of theoretical techniques. Symmetry-adapted perturbation theory (SAPT0) calculations confirmed more favorable adsorption of Tax on N-doped graphenes compared to pristine graphene. It was established that dispersion interactions play the main role in the attractive interactions (>60%), whereas electrostatic and induction forces contribute only moderately to the attraction (~25% and 7–8%, respectively). Independent gradient model (IGM) analysis visually demonstrated the existence of dispersion interactions and hydrogen bonding in the studied Tax complexes. Ab initio molecular dynamics calculations indicated stability of these complexes at different temperatures. Our results show that N-doped graphenes with the enhanced interaction energy (Eint) toward Tax are promising candidates for the technical realization of the targeted drug delivery systems. [ABSTRACT FROM AUTHOR]

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Background: Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. Methods and results: DM was induced in eighteen rats through intraperitoneal injections of 50 mg/kg streptozotocin and 110 mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50 mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. Conclusions: TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50 mg/kg TXF was more effective than 25 mg/kg and is recommended for consumption. [ABSTRACT FROM AUTHOR]

Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout. Methods The pharmacological model of hyperuricemia was established. The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS. Based on the components absorbed in blood, the “active ingredient-target-pathway” network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method. The key ingredients were used for molecular docking with key targets [uricogenase (XDH), uric acid transporter (ABCG2, GLUT9, OAT1, URAT1) and inflammatory targets (PTGS2, TLR2, TLR4)] of hyperuricemia and gout. Finally, experimental verification was conducted according to the results of molecular docking. Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout. Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis, including 74 components absorbed in blood, which were confirmed as candidate ingredients. Network pharmacology was used to constructed “components absorbed in blood-target-pathway” network, and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout. It is involved in the regulation of biological processes, such as glucose and lipid metabolism, oxidative stress, inflammatory response, ERK1 and ERK2 cascade, MAPK cascade, PI3K signal transduction. Moreover, Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis, apoptosis, AGE-RAGE, TNF, PI3K-Akt, MAPK, TLRs, JAK-STAT, NF- κB and other signaling pathways. Molecular docking studies showed that berberine, phellodendrine, magnoflorine, jatrorrhizine, palmatine, obacunone, limonin, atractylodin, taxifolin, atractylenolide Ⅲ and β -ecdysterone had good affinity with uric acid synthase, uric acid transporter and inflammatory targets. Western Blot test showed that taxifolin negatively regulates the expression of URAT1. The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout. Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout, which can provides a scientific basis for the clinical application, improvement in quality evaluation and standard of Simiao Wan. [ABSTRACT FROM AUTHOR]

Transmembrane protease/serine (TMPRSS2), a type II transmembrane serine protease, plays a crucial role in different stages of cancer. Recent studies have reported that the triggering epidermal growth factor receptor (EGFR) activation through protease action promotes metastasis. However, there are no reports on the interaction of TMPRSS2 with EGFR, especially in triple‐negative triple negative (TNBC). The current study investigates the unexplored interaction between TMPRSS2 and EGFR, which are key partners mediating metastasis. This interaction is explored for potential targeting using quercetin (QUE) and taxifolin (TAX). TMPRSS2 expression patterns in breast cancer (BC) tissues and subtypes have been predicted, with the prognostic significance assessed using the GENT2.0 database. Validation of TMPRSS2 expression was performed in normal and TNBC tissues, including drug‐resistant cell lines, utilizing GEO datasets. TMPRSS2 was further validated as a predictive biomarker for FDA‐approved chemotherapeutics through transcriptomic data from BC patients. The study demonstrated the association of TMPRSS2 with EGFR through in silico analysis and validates the findings in TNBC cohorts using the TIMER2.0 web server and the TCGA dataset through C‐Bioportal. Molecular docking and molecular dynamic simulation studies identified QUE and TAX as best leads targeting TMPRSS2. They inhibited cell‐free TMPRSS2 activity like clinical inhibitor of TMPRSS2, Camostat mesylate. In cell‐based assays focused on paclitaxel‐resistant TNBC (TNBC/PR), QUE and TAX demonstrated potent inhibitory activity against extracellular and membrane‐bound TMPRSS2, with low IC50 values. Furthermore, ELISA and cell‐based AlphaLISA assays demonstrated that QUE and TAX inhibit the interaction of TMPRSS2 with EGFR. Additionally, QUE and TAX exhibited significant inhibition of proliferation and cell cycle accompanied by notable alterations in the morphology of TNBC/PR cells. This study provides valuable insights into potential of QUE and TAX targeting TMPRSS2 overexpressing TNBC. [ABSTRACT FROM AUTHOR]

Background. Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its pathogenesis. Taxifolin is a flavonoid that exhibits antioxidant activity. Objectives. To investigate the effects of taxifolin on caffeine-induced epileptic seizures in rats and reveal the role of antioxidant activity in antiepileptic therapy. Materials and methods. Forty rats were divided into 4 groups (n = 6/group): caffeine 300 mg/kg group (CG), taxifolin 50 mg/kg + caffeine 300 mg/kg group (TCG), 2 mg/kg diazepam + 300 mg/kg caffeine group (DCG), and a healthy group (HG). Taxifolin was given to the TCG, and diazepam was given to the DCG orally. One hour later, caffeine was injected intraperitoneally into the CG, TCG and DCG rats. The time between the caffeine injection and the contractions (the latency period) was determined. Animals were euthanized 1 h after caffeine injection, and brain tissues were biochemically examined for oxidants and antioxidants. Results. Taxifolin and diazepam prolonged the latency period to a similar extent (p = 0.549), while taxifolin was more successful in preventing mortality. Taxifolin suppressed the caffeine-induced increase in myeloperoxidase, total oxidant status and oxidative stress index, and decreased total glutathione, superoxide dismutase and total antioxidant status more effectively than diazepam (p < 0.05). Conclusions. We showed the relationship between antioxidant activity and epilepsy treatment, and demonstrated that taxifolin may be useful for treating epilepsy. [ABSTRACT FROM AUTHOR]

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be −4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD. [ABSTRACT FROM AUTHOR]

Background: Mammary carcinoma is the most frequently diagnosed form of carcinoma in women worldwide. The organometallic compounds showed a prospective anticancer activity. This research explored the anticancer efficacy of taxifolin ruthenium-p-cymene counter to breast cancer. Methods: The anticancer efficacy of the novel organometallic compound was investigated via various in vitro and in vivo techniques using breast cancer cell lines and breast cancer model of rat. Results: Target proteins were identified via pharmacophore analysis, which revealed a high binding affinity towards AhR, EGFR, and β-catenin. The compound induced apoptotic events and prevented cancer cell colony formation. Furthermore, decreased expression of AhR, EGFR, and N-cadherin inhibited cancer cell growth, migration, and proliferation. The compound provoked the cell cycle arrest at sub G0/G1 phase, S phase and G2/M phase and inaugurated the caspase-3 dependent apoptotic events. The in-vivo experimentation displayed the fruitful restoration of breast tissue since the complex treatment in DMBA persuaded breast carcinoma in rat. Moreover, the upstream of p53 and caspase-3 expression along with substantially downstream of vimentin, β-catenin, m-TOR and Akt expression. Conclusions: In conclusion, the compound repressed the cancerous cellular viability, migration, and EMT via modulating the AhR/EGFR/ PI3K transduction pathway and the expression of EMT biomarkers such as N-cadherin, E-cadherin, thus eventually revoked the EMT facilitated metastasis of malignant cells.

Introduction. The structure of dihydroquercetin (DHQ) is characterized by two chiral centers at positions 2 and 3 of the benzopyran cycle, resulting in possible diastereomers: trans- and cis-isomers. Therefore, the development of methods for qualitative and quantitative control of DHQ diastereomers in analyzed samples is essential for patient safety management. Nuclear magnetic resonance (NMR) spectroscopy is one of the physicochemical methods that can be used for this purpose.Aim. The study objective was to accumulate the analytical and structural characteristics of cis-DHQ by NMR spectroscopy of the spheroidal form of this flavonoid (DHQs).Materials and Methods. 1D 1H, 1H,1H-COSY, 1H,1H-NOESY, and 1H,13C-HSQC NMR spectra were acquired at 298 K on an 800 MHz NMR spectrometer equipped with a TXI triple resonance probe. The number of scans was 32. The mixing time in the NOESY experiment was 400 ms. The 1H and 13C were analyzed using CcpNmr software. The dihedral angles were calculated by applying the Karplus equation.Results and discussion. In trans-DHQ, the chemical shift values for H2 and H3 are 4.93 ppm and 4.52 ppm, respectively, and in cis-DHQ they are 5.31 ppm and 4.20 ppm, respectively. The spin-spin coupling constants between H2 and H3 of trans- and cis-DHQ are 12.00 Hz and 2.40 Hz, respectively. Thus, the dihedral angles for the trans- and cis-isomers are 154° and 64°, respectively. We found that DHQs contains 12.5 % of the cis-isomer.Conclusion. Our experiments confirmed that NMR spectroscopy can discriminate between trans- and cis-DHQ based on the chemical shift values for the cross-peaks of H2 and H3. The second major finding was that this method can be considered as a more selective quantitative analysis than HPLC with UV detection without reference. One of the most important results of this study for drug development is the updated information on the structural parameters of DHQ diastereomers in the liquid phase.

• Antioxidant and anti-inflammatory activities of Crotalaria medicaginea are reported. • Dichloromethane, acetone and methanol fractions were strong antioxidants. • All the extracts produced strong anti-inflammatory effects with minimum hemolysis. • GC–MS analysis of total extract showed presence of bioactive compounds. • HPLC-DAD analysis confirmed the presence of phenolic compounds in the plant. Inflammation is the underlying process to many degenerative diseases such as emphysema, cancer, Alzheimer's, arthritis, diabetes, and more recently COVID-19. The overproduction of free radicals in the cells is the major factor that leads to inflammation due to oxidative stress. These free radicals damage macromolecules in cells, including nucleic acids, proteins, lipids, and polyunsaturated fatty acids, through oxidation, thus affecting cell metabolism. Antioxidants can delay the oxidation of these molecules through inhibition of oxidizing chain reactions and can be helpful in treating inflammatory diseases. Crotalaria medicaginea Lamk (Fabaceae) is an important medicinal plant that is not extensively explored for its biological and pharmacological potential on scientific grounds. In this study, in vitro antioxidant and anti-inflammatory activities of the crude methanolic extract and different solvent fractions of the plant were determined. Phenolics, flavonoids, tannins, and saponins were quantified in each plant sample. The crude extract was characterized for its phytochemical constituents through GC–MS and HPLC analysis. Strong antioxidant and anti-inflammatory activities of plant extracts were recorded which can be attributed to the presence of phenolics, flavonoids, saponins, terpenes, and tannins in these extracts. GC–MS analysis confirmed the presence of Hexadecanoic acid, methyl ester, 9,12-Octadecadienoic acid (Z,Z)-, methyl ester, and 9-Octadecenoic acid, methyl ester, (E)- as major compounds while HPLC analysis confirmed the presence of gallic acid, taxifolin, quercetin and kaempferol in the plant. [ABSTRACT FROM AUTHOR]

α‐Tocopherol (α‐TOC) and myricetin (MYR) synergistically inhibit lipid oxidation in bulk oil but the mechanism underlying this effect is unknown. In this research, stripped soybean oil (SSO) was treated with α‐tocopherol (50 μM), myricetin (10–250 μM), and their combinations. Taxifolin (TAX) was also tested because it has structural similarities to myricetin but with a higher redox potential. α‐Tocopherol: myricetin ratios of 5:1, 2:1, 1:1, 1:2, and 1:5 resulted in extended lag phases ranging from 16 to 99 days, with lag phase increasing with increasing myricetin concentrations. Synergism between α‐tocopherol and myricetin was also observed in phospholipid‐containing bulk oils both in the absence and presence of reverse micelles, although the reverse micelles shortened the lag phases. Myricetin (redox potential = 360 mV) delayed the oxidation of α‐tocopherol (redox potential = 500 mV) whereas taxifolin (redox potential = 500 mV) did not. Both myricetin and taxifolin were able to chelate iron as determined by UV–VIS spectroscopy. These results suggested that the lower redox potential of myricetin allowed it to produce synergistic antioxidant activity potentially by regenerating oxidized α‐tocopherol and through its ability to decrease oxidation by metal chelation. [ABSTRACT FROM AUTHOR]

Aromadendrin and taxifolin are two flavanonols (derived from the precursor naringenin) displaying diverse beneficial properties for humans. The carbon skeleton of these flavonoids may be transformed by the human gastrointestinal microbiota into other compounds, like auronols, which exert different and interesting biological activities. While research in flavonoids has become a certainly extensive field, studies about auronols are still scarce. In this work, different versions of the key plant enzyme for flavanonols biosynthesis, The flavanone 3-hydroxylase (F3H), has been screened for selecting the best one for the de novo production of these compounds in the bacterial factory Streptomyces albidoflavus UO-FLAV-004-NAR, a naringenin overproducer strain. This screening has rendered 2.6 µg/L of aromadendrin and 2.1 mg/L of taxifolin final production titers. Finally, the expression of the chalcone isomerase (CHI) from the gut bacterium Eubacterium ramulus has rendered a direct conversion (after feeding experiments) of 38.1% of (+)-aromadendrin into maesopsin and 74.6% of (+)-taxifolin into alphitonin. Moreover, de novo heterologous biosynthesis of 1.9 mg/L of alphitonin was accomplished by means of a co-culture strategy of a taxifolin producer S. albidoflavus and a CHI-expressing Escherichia coli, after the observation of the high instability of alphitonin in the culture medium. This study addresses the significance of culture time optimization and selection of appropriate enzymes depending on the desired final product. To our knowledge, this is the first time that alphitonin de novo production has been accomplished. [ABSTRACT FROM AUTHOR]

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial 11C-Pittsburgh compound B positron emission tomography (11-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-β (Aβ) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial 11-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aβ-clearing therapeutic agents such as taxifolin. [ABSTRACT FROM AUTHOR]

Melatonin is a multifunctional hormone regulator that maintains homeostasis through circadian rhythms, and desynchronization of these rhythms can lead to gastrointestinal disorders and increase the risk of cancer. Preliminary clinical studies have shown that exogenous melatonin alleviates the harmful effects of anticancer therapy and improves quality of life, but the results are still inconclusive due to the heterogeneity of the studies. A personalized approach to testing clinical parameters and response to integrative treatment with nontoxic and bioavailable melatonin in patient-centered N-of-1 studies deserves greater attention. This clinical case of colon cancer analyzes and discusses the tumor pathology, the adverse effects of chemotherapy, and the dynamics of markers of inflammation (NLR, LMR, and PLR ratios), tumors (CEA, CA 19-9, and PSA), and hemostasis (D-dimer and activated partial thromboplastin time). The patient took melatonin during and after chemotherapy, nutrients (zinc, selenium, vitamin D, green tea, and taxifolin), and aspirin after chemotherapy. The patient's PSA levels decreased during CT combined with melatonin (19 mg/day), and melatonin normalized inflammatory markers and alleviated symptoms of polyneuropathy but did not help with thrombocytopenia. The results are analyzed and discussed in the context of the literature on oncostatic and systemic effects, alleviating therapy-mediated adverse effects, association with survival, and N-of-1 studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Deoxynivalenol (DON), a common mycotoxin widely found in feed, often causes intestinal oxidative damage, and the utilization of antioxidants is one way to reduce this damage. Taxifolin (TA) is a flavanone with tremendous antioxidant capacity. The aim of the current study was to explore whether TA alleviates DON-induced damage in porcine intestinal epithelial cells (IPEC-J2) and, if so, the underlying mechanism. Our results demonstrated that TA attenuated DON-induced cellular damage via suppressing the DON-induced declines in IPEC-J2 cell viability and proliferation, cellular apoptosis, and reactive oxygen species (ROS) production; the decline in cellular barrier function; and the decrease in antioxidant status. Collectively, our findings suggest that the damage caused by DON in the IPEC-J2 cells could be alleviated by TA, potentially through the activation of the Nrf2 signaling pathway. Deoxynivalenol (DON) contamination in feed is a global concern that severely threatens the health of animals and humans. Taxifolin (TA) is a natural flavonoid, a member of the polyphenols, that possesses robust antioxidant properties. This study aimed to investigate the effect of TA on DON-induced damage in porcine intestinal epithelial cells (IPEC-J2). The cells were pre-incubated with a series of concentrations of TA for 24 h and exposed to DON (0.5 μg/mL) for another 24 h. The results showed that pretreatment with TA (150 μM) significantly inhibited the DON-induced decline in cell viability (p < 0.05) and cell proliferation (p < 0.01). Additionally, 150 μM TA also alleviated DON-induced apoptosis (p < 0.01). Moreover, TA decreased the production of reactive oxygen species (ROS) induced by DON (p < 0.01). In addition, TA attenuated DON-induced cell junction damage (p < 0.05). Further experiments showed that TA reversed the DON-induced reduction in antioxidant capacity in the IPEC-J2 cells, probably via activating the Nrf2 signaling pathway (p < 0.05). Collectively, these findings suggest that 150 μM TA can protect against 0.5 μg/mL DON-induced damage to IPEC-J2 cells, potentially via the activation of the Nrf2 signaling pathway. This study provides insight into TA's potential to act as a green feed additive in the pig farming industry and its efficacy in counteracting DON-induced intestinal damage. [ABSTRACT FROM AUTHOR]