Naringin is an antioxidant flavonoid rich in diverse plant species, including citrus plants. While the antioxidant activity of naringin is well documented, there has been limited research on its anti-aging potential. The aim of this study is to investigate the in vivo anti-aging effects of naringin in the budding yeast Saccharomyces cerevisiae as a model. Our findings showed that naringin substantially increased cell viability during the chronological lifespan of wild-type yeast by mitigating oxidative and apoptotic stress markers. However, naringin did not affect the viability of yeast null mutants lacking antioxidant enzymes (sod2Δ, cta1Δ, ctt1Δ, gpx1Δ, gpx2Δ, gsh1Δ; except sod1Δ and tsa1Δ), but slightly increased the viability of only pep4Δ and fis1Δ mutants, not mca1Δ. Gene expression results indicate that naringin altered the expression of genes associated with the TORC1 signaling pathway and other anti-aging genes such as SIR2 and ATG1. The study's findings also demonstrate that naringin could not increase cell viability of yeast null mutants lacking signaling pathway genes (tor1Δ, rim15Δ ras2Δ, and atg1Δ), except sch9Δ mutant during CLS. Metabolomic studies suggest that naringin treatment affects the levels of diverse class of metabolites such as amino acids, nucleotides and related compounds, vitamins, carbohydrates, and lipids in stationary phase yeast. Altogether, these findings suggest that naringin might exerts its anti-aging effects via modulating the nutrient sensing TORC1 signaling pathway, paving the way for future research to explore other aging associated gene targets.

• Keywords
• Saccharomyces cerevisiae, Aging, Apoptosis, Naringin, Oxidative stress, Target of rapamycin,
• MeSH
• Antioxidants * pharmacology   MeSH
• Flavanones * pharmacology   MeSH
• Oxidative Stress drug effects   MeSH
• Saccharomyces cerevisiae Proteins genetics   metabolism   MeSH
• Saccharomyces cerevisiae * drug effects   genetics   metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Aging * drug effects   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants * MeSH
• Flavanones * MeSH
• naringin MeSH Browser
• Saccharomyces cerevisiae Proteins MeSH

Hepatic fibrosis progresses concomitantly with a variety of biomechanical alternations, especially increased liver stiffness. These biomechanical alterations have long been considered as pathological consequences. Recently, growing evidence proposes that these alternations result in the fibrotic biomechanical microenvironment, which drives the activation of hepatic stellate cells (HSCs). Here, an inorganic ascorbic acid-oxidase (AAO) mimicking nanozyme loaded with liquiritigenin (LQ) is developed to trigger remodeling of the fibrotic biomechanical microenvironment. The AAO mimicking nanozyme is able to consume intracellular ascorbic acid, thereby impeding collagen I deposition by reducing its availability. Simultaneously, LQ inhibits the transcription of lysyl oxidase like 2 (LOXL2), thus impeding collagen I crosslinking. Through its synergistic activities, the prepared nanosystem efficiently restores the fibrotic biomechanical microenvironment to a near-normal physiological condition, promoting the quiescence of HSCs and regression of fibrosis. This strategy of remodeling the fibrotic biomechanical microenvironment, akin to "pulling the rug out from under", effectively treats hepatic fibrosis in mice, thereby highlighting the importance of tissue biomechanics and providing a potential approach to improve hepatic fibrosis treatment.

• Keywords
• biomechanical microenvironment, collagen I, hepatic fibrosis, hepatic stellate cell quiescence,
• MeSH
• Biomechanical Phenomena MeSH
• Cellular Microenvironment drug effects   MeSH
• Flavanones pharmacology   chemistry   MeSH
• Liver Cirrhosis * drug therapy   metabolism   pathology   MeSH
• Hepatic Stellate Cells * metabolism   cytology   drug effects   MeSH
• Collagen Type I metabolism   MeSH
• Ascorbic Acid * pharmacology   metabolism   chemistry   MeSH
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Flavanones MeSH
• Collagen Type I MeSH
• Ascorbic Acid * MeSH

BACKGROUND: Venotonics are a class of therapeutically active molecules that have vaso-protective effects. They are used to alleviate venous diseases and disorders, particularly venous insufficiency. We compared the composition of prescription versus over-the-counter (OTC) venotonics using high-performance liquid chromatography with UV detection (HPLC-DAD) and simulating their digestion using a static digestive model. METHODS: From each drug, five tablets were weighed. A homogenate was prepared, and 25 mg of crushed homogenized tablets were weighed into 25 ml volumetric flasks. Dissolved in MeOH and added two drops of saturated NaOH solution. The samples were filtered into vials (Teflon, 0.45 μm) and used for analysis. An Ultimate 3000 HPLC system (Thermo Fisher Scientific, Waltham, MA, USA) consisting of a quaternization pump, autosampler, column thermostat and DAD (UV/VIS detector) was used. The composition of the mobile phase proceeded in a linear gradient from 30% methanol and 70% phosphoric acid (0.15%) in water at time t=0 min. to 80% methanol and 20% phosphoric acid (0.15%) at time t=15 min., at a constant mobile phase flow rate of 1.2 mL/min. Detection was performed using a DAD detector in the 190-450 nm wavelength range. The content of monitored flavonoids was calculated from peaks at a wavelength of 277 nm, in which both flavonoids have their absorption maxima. The static digestive model was used to simulate the digestive phase from the oral cavity to the corresponding intestinal phase. RESULTS: The content of diosmin and hesperidin (mg per table) for a prescription drug: Detralex: 480 mg, 26 mg. The content of diosmin and hesperidin (mg per tablet) for OTC drugs: Venostop: 502 mg, 48 mg, Diosminol: 520 mg, 50 mg, Devenal: 496 mg, 49 mg, Diohes: 493 mg, 46 mg. Digestion did not affect the solubility of all tested drugs. The active substances could not be determined in the non-alkalized sample. After alkalization, part of the insoluble matter was visibly dissolved and converted to a yellow flavonoid complex. Neither diosmin nor hesperidin could be identified afterwards. CONCLUSIONS: Our experimental results show that the contents of both listed active substances, diosmin and hesperidin, met the declared amounts in all tested medicaments. Digestion simulation showed identical behaviour in prescription and OTC venotonics. The active substances could not be determined in the non-alkalized sample. Digestion did not affect the solubility of the tested drugs.

• MeSH
• Models, Biological MeSH
• Diosmin analysis   MeSH
• Hesperidin analysis   MeSH
• Nonprescription Drugs * chemistry   MeSH
• Prescription Drugs analysis   chemistry   MeSH
• Humans MeSH
• Tablets MeSH
• Chromatography, High Pressure Liquid MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Diosmin MeSH
• Hesperidin MeSH
• Nonprescription Drugs * MeSH
• Prescription Drugs MeSH
• Tablets MeSH

Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.

• Keywords
• Anti-cancer, Cellular effects, Copper(II), Diplacone, In vitro cytotoxicity, Inflammation,
• MeSH
• Anti-Inflammatory Agents pharmacology   chemistry   MeSH
• Autophagy drug effects   MeSH
• Flavanones * pharmacology   chemistry   MeSH
• Coordination Complexes * pharmacology   chemical synthesis   chemistry   MeSH
• Humans MeSH
• Copper * chemistry   pharmacology   MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation * drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemistry   chemical synthesis   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Inflammatory Agents MeSH
• Flavanones * MeSH
• Coordination Complexes * MeSH
• Copper * MeSH
• Antineoplastic Agents * MeSH
• Reactive Oxygen Species MeSH

Onosma riedliana Binzet & Orcan, a traditionally used plant species, has been explored for its therapeutic potential in this study. The work presented here is the first report on the phenolic profile and biological activity of this species. Three extracts of varying polarity were prepared, with the methanolic extract containing the highest phenolic content (97.62 ± 0.20 mgGAE/g). Key phenolic compounds identified included pinoresinol, hesperidin, 4-hydroxybenzoic acid, and p-coumaric acid. The methanolic extract exhibited exceptional antioxidant properties, rivaling Trolox as a positive control, primarily attributed to hesperidin and luteolin. Moreover, the ethyl acetate extract demonstrated remarkable inhibition of cholinesterase and tyrosinase enzymes, while the methanolic extract displayed potent activity against carbohydrate hydrolytic enzymes, α-amylase and α-glucosidase. Again, phenolic compounds were shown to be responsible for the inhibition of cholinesterases and tyrosinase, but not for α-amylase and α-glucosidase. These findings underscore Onosma riedliana's potential for incorporation into diverse pharmaceutical formulations, given its multifaceted bioactivity.

• Keywords
• Antioxidant Activity, Enzyme Inhibitory Activity, Onosma Riedliana, Phenolic Compounds,
• MeSH
• alpha-Amylases MeSH
• alpha-Glucosidases MeSH
• Antioxidants pharmacology   MeSH
• Phenols pharmacology   MeSH
• Hesperidin * MeSH
• Enzyme Inhibitors * pharmacology   MeSH
• Methanol MeSH
• Plant Extracts pharmacology   MeSH
• Monophenol Monooxygenase metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• alpha-Amylases MeSH
• alpha-Glucosidases MeSH
• Antioxidants MeSH
• Phenols MeSH
• Hesperidin * MeSH
• Enzyme Inhibitors * MeSH
• Methanol MeSH
• Plant Extracts MeSH
• Monophenol Monooxygenase MeSH

Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.

• Keywords
• hesperetin, hesperidin, normal human dermal fibroblast, rhamnose, rutinose, skin aging,
• MeSH
• Hesperidin * pharmacology   MeSH
• Hyaluronoglucosaminidase MeSH
• Collagenases metabolism   MeSH
• Humans MeSH
• Pancreatic Elastase MeSH
• Rhamnose * pharmacology   MeSH
• Skin Aging * drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• hesperetin MeSH Browser
• Hesperidin * MeSH
• Hyaluronoglucosaminidase MeSH
• Collagenases MeSH
• Pancreatic Elastase MeSH
• Rhamnose * MeSH
• rutinose MeSH Browser

Metabolic syndrome is diagnosed mainly in people of economically developed parts of the world and it affects 20-25% of the adult population worldwide. Nowadays, it is also more frequently diagnosed in children and adolescents. In addition to standard treatment that often involves polypharmacotherapy, and thus increases risk of side effects caused by drugdrug interactions, it is appropriate to look for alternative tools to support the treatment of metabolic syndrome components. Natural polyphenolic compounds, usually present in the so-called functional foods, are suitable candidates for that matter, due to the bioactivity and beneficial effects on the human body. Quercetin, troxerutin, diosmin, hesperidin or silybin are among the currently studied and used natural polyphenolic compounds with a positive effect on aspects of the metabolic syndrome. In addition to their antioxidant and anti-inflammatory effects, these compounds have other positive properties that very often outweigh their side effects whilst their usage in the pharmacotherapy.

• Keywords
• NAFLD, diosmin, metabolic syndrome, polyphenolic compounds, quercetin, silymarin, troxerutin,
• MeSH
• Anti-Inflammatory Agents MeSH
• Antioxidants adverse effects   MeSH
• Diosmin * therapeutic use   MeSH
• Child MeSH
• Adult MeSH
• Hesperidin * therapeutic use   MeSH
• Humans MeSH
• Metabolic Syndrome * drug therapy   MeSH
• Adolescent MeSH
• Quercetin MeSH
• Silybin therapeutic use   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Inflammatory Agents MeSH
• Antioxidants MeSH
• Diosmin * MeSH
• Hesperidin * MeSH
• Quercetin MeSH
• Silybin MeSH

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

• Keywords
• 8-prenylnaringenin, desmethylxanthohumol, estrogenic activity, hop, phytoestrogens, prenylflavonoids,
• MeSH
• Flavanones chemistry   metabolism   MeSH
• Flavonoids chemistry   metabolism   MeSH
• Phytoestrogens chemistry   metabolism   MeSH
• Humulus chemistry   MeSH
• Catalysis MeSH
• Humans MeSH
• Magnesium Oxide chemistry   metabolism   MeSH
• Beer analysis   MeSH
• Dietary Supplements analysis   MeSH
• Propiophenones chemistry   metabolism   MeSH
• Plant Extracts metabolism   MeSH
• Plant Preparations chemistry   metabolism   MeSH
• Temperature MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 8-prenylnaringenin MeSH Browser
• Flavanones MeSH
• Flavonoids MeSH
• Phytoestrogens MeSH
• Magnesium Oxide MeSH
• Propiophenones MeSH
• Plant Extracts MeSH
• Plant Preparations MeSH
• xanthohumol MeSH Browser

Geranylated flavanone diplacone is a flavanone iso- lated from Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) with anti-inflammatory and antioxidant properties, nevertheless showing high lipophilicity and low solubility in water. Diplacone was therefore used as a model molecule for incorporation into glucan particles (GPs). GPs are prepared by intensive washing of yeast (Saccharomyces cerevisiae) leading to hollow shells consisting of β-(13)/β-(16) glucan mainly. The aim of this study was to compare anti-inflammatory potential of GPs-diplacone composites with the compound itself, GPs themselves and the physical mixture of GPs and diplacone. The cell line THP1-XBlueTM-MD2-CD14 derived from human leukemic monocytes was stimulated with lipopolysaccharide (LPS) from Escherichia coli to trigger inflammatory reaction. The composites of GPs with diplacone significantly decreased the activity of pro-inflammatory transcription factors nuclear factor κB (NF-κB) and activator protein 1 (AP-1).

• Keywords
• AP-1, NF-κB, diplacone, encapsulation, glucan particles, inflammation,
• MeSH
• Anti-Inflammatory Agents pharmacology   MeSH
• Flavanones pharmacology   MeSH
• Glucans chemistry   MeSH
• Humans MeSH
• NF-kappa B metabolism   MeSH
• Saccharomyces cerevisiae chemistry   MeSH
• THP-1 Cells MeSH
• Transcription Factor AP-1 metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Inflammatory Agents MeSH
• diplacone MeSH Browser
• Flavanones MeSH
• Glucans MeSH
• NF-kappa B MeSH
• Transcription Factor AP-1 MeSH

The intake of flavanones, the predominant flavonoid in the Citrus genus in human diets is variable but considerable. It is thus unsurprising that they have attracted interest for their claimed positive effects on health. However, to substantiate any purported impact on health and decipher the underlying mechanism(s), knowledge of pharmacokinetics is crucial. The aim of this article is to review currently known aspects of the fate of flavanones in the organism including absorption, metabolism, distribution, and excretion as well as possible kinetic interactions with clinically used drugs. There are three principal keynotes: (1) The level of parent flavanones in plasma is negligible. The major reason for this is that although flavanones are absorbed into enterocytes after oral intake, they are rapidly metabolized, in particular, into conjugates, sulfates and glucuronides, which are the major forms circulating in plasma. (2) A large fraction reaches the colon where it is efficiently metabolized into small absorbable phenolics. (3) The form (aglycone vs. glycoside) and species (e.g. human vs. rat) have important impact. In conclusion, knowledge of the pharmacokinetics of flavanones, in particular of metabolites, their achievable plasma concentration and half-lives, should be borne in mind when their biological effects are investigated.

• Keywords
• Absorption, hesperetin, hesperidin, metabolites, naringenin, naringin,
• MeSH
• Citrus * MeSH
• Diet MeSH
• Flavanones * MeSH
• Flavonoids MeSH
• Hesperidin * MeSH
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Flavanones * MeSH
• Flavonoids MeSH
• Hesperidin * MeSH