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

2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: in general, DHS appeared to be a more potent iron and copper chelator, and a copper reducing agent under acidic conditions, while DHSCH was a more potent copper reducing agent under neutral conditions. In the next step, both DHS and DHSCH were tested for metal-based Fenton chemistry in vitro using HPLC with coulometric detection. Neither of these compounds were able to block the iron-based Fenton reaction and, in addition, they mostly intensified hydroxyl radical production. In the copper-based Fenton reaction, the effect of DHSCH was again prooxidant or neutral, while the effect of DHS was profoundly condition-dependent. DHS was even able to attenuate the reaction under some conditions. Interestingly, both compounds were strongly protective against the copper-triggered lysis of red blood cells, with DHSCH being more potent. The results from this study indicated that, notwithstanding the prooxidative effects of both dehydroflavonolignans, their in vivo effect could be protective.

• Keywords
• copper, dehydroflavonolignans, dehydrosilybin, dehydrosilychristin, flavonolignans, hydroxyl radical, iron, milk thistle, prooxidation, silymarin,
• Publication type
• Journal Article MeSH

The consumption of herbal-based supplements, which are believed to have beneficial effects on human health with no side effects, has become popular around the world and this trend is still increasing. Silybum marianum (L.) Gaertn, commonly known as milk thistle (MT), is the most commonly studied herb associated with the treatment of liver diseases. The hepatoprotective effects of active substances in silymarin, with silybin being the main compound, have been demonstrated in many studies. However, MT can be affected by toxigenic micro-fungi and contaminated by mycotoxins with adverse effects. The beneficial effect of silymarin can thus be reduced or totally antagonized by mycotoxins. MT has proven to be affected by micro-fungi of the Fusarium and Alternaria genera, in particular, and their mycotoxins. Alternariol-methyl-ether (AME), alternariol (AOH), beauvericin (BEA), deoxynivalenol (DON), enniatin A (ENNA), enniatin A1 (ENNA1), enniatin B (ENNB), enniatin B1 (ENNB1), HT-2 toxin (HT-2), T-2 toxin (T-2), tentoxin (TEN), and zearalenone (ZEA) seem to be most significant in MT-based dietary supplements. This review focuses on summarizing cases of mycotoxins in MT to emphasize the need for strict monitoring and regulation, as mycotoxins in relation with MT-based dietary supplements are not covered by European Union legislation.

• Keywords
• food supplements, liver diseases, milk thistle, mycotoxins, silymarin,
• MeSH
• European Union MeSH
• Humans MeSH
• Mycotoxins adverse effects   analysis   MeSH
• Silybum marianum adverse effects   MeSH
• Dietary Supplements adverse effects   analysis   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Mycotoxins MeSH

Herbal preparations from Silybum marianum have been used since the fourth century BC in liver disease treatment and against numerous other pathologies. Consumption of silymarin containing drugs and food supplements continues to increase. Precise, fast, reliable, and complex determination of all components of silymarin preparations is paramount for assessing its pharmacological quality. We present here simple and fast HPLC-DAD and LC-MS analytical methods for the determination and quantification of all known silymarin components, including 2,3-dehydroflavonolignans that has not been achieved so far. The first method, using a common C18 column, allows baseline separation of previously inseparable silychristin A, B, isosilychristin, and silydianin. Moreover, this method allowed detection of three so far unknown silymarin components. In addition, the first analytical separation of enantiomers of 2,3-dehydrosilybin was achieved using a Lux 3μ Cellulose-4 chiral column, providing even more accurate description of silymarin composition. 2,3-Dehydroflavonolignans were isolated for the first time from silymarin using preparative chromatography on C18 and ASAHIPAK columns, and 2,3-dehydrosilychristin and 2,3-dehydrosilybin were for the first time conclusively confirmed by HPLC, MS, and NMR to be silymarin components. Using the optimized analytical methods, six various silymarin preparations were analyzed showing substantial differences in the composition.

• Keywords
• HPLC-MS separation, diastereoisomers, enantiomers, flavonolignans, milk thistle, quantification, silymarin,
• Publication type
• Journal Article MeSH

Silychristin A is the second most abundant compound of silymarin. Silymarin complex was previously described as an antioxidant with multidrug resistance modulation activity. Here, the results of a classical biochemical antioxidant assay (ORAC) were compared with a cellular assay evaluating the antioxidant capacity of pure silychristin A and its derivatives (anhydrosilychristin, isosilychristin and 2,3-dehydrosilychristin A). All the tested compounds acted as antioxidants within the cells, but 2,3-dehydro- and anhydro derivatives were almost twice as potent as the other tested compounds. Similar results were obtained in LPS-stimulated macrophages, where 2,3-dehydro- and anhydrosilychristin inhibited NO production nearly twice as efficiently as silychristin A. The inhibition of P-glycoprotein (P-gp) was determined in vitro, and the respective sensitization of doxorubicin-resistant ovarian carcinoma overproducing P-gp was detected. Despite the fact that the inhibition of P-gp was demonstrated in a concentration-dependent manner for each tested compound, the sensitization of the resistant cell line was observed predominantly for silychristin A and 2,3-dehydrosilychristin A. However, anhydrosilychristin and isosilychristin affected the expression of both the P-gp (ABCB1) and ABCG2 genes. This is the first report showing that silychristin A and its 2,3-dehydro-derivative modulate multidrug resistance by the direct inhibition of P-gp, in contrast to anhydrosilychristin and isosilychristin modulating multidrug resistance by downregulating the expression of the dominant transmembrane efflux pumps.

• Keywords
• ABC superfamily, Adriamycin, BCRP, P-glycoprotein, expression profile, immunomodulation, silychristin, silymarin,
• Publication type
• Journal Article MeSH