Silybin A

Silybin regulates P450s activity by attenuating endoplasmic reticulum stress in mouse nonalcoholic fatty liver disease.[Pubmed:35705686]

Acta Pharmacol Sin. 2022 Jun 15. pii: 10.1038/s41401-022-00924-4.

Cytochrome P450s are important phase I metabolic enzymes located on endoplasmic reticulum (ER) involved in the metabolism of endogenous and exogenous substances. Our previous study showed that a hepatoprotective agent silybin restored CYP3A expression in mouse nonalcoholic fatty liver disease (NAFLD). In this study we investigated how silybin regulated P450s activity during NAFLD. C57BL/6 mice were fed a high-fat-diet (HFD) for 8 weeks to induce NAFLD, and were administered silybin (50, 100 mg .kg(-1) .d(-1), i.g.) in the last 4 weeks. We showed that HFD intake induced hepatic steatosis and ER stress, leading to significant inhibition on the activity of five primary P450s including CYP1A2, CYP2B6, CYP2C19, CYP2D6, and CYP3A in liver microsomes. These changes were dose-dependently reversed by Silybin Administration. The beneficial effects of silybin were also observed in TG-stimulated HepG2 cells in vitro. To clarify the underlying mechanism, we examined the components involved in the P450 catalytic system, membrane phospholipids and ER membrane fluidity, and found that cytochrome b5 (cyt b5) was significantly downregulated during ER stress, and ER membrane fluidity was also reduced evidenced by DPH polarization and lower polyunsaturated phospholipids levels. The increased ratios of NADP(+)/NADPH and PC/PE implied Ca(2+) release and disruption of cellular Ca(2+) homeostasis resulted from mitochondria dysfunction and cytochrome c (cyt c) release. The interaction between cyt c and cyt b5 under ER stress was an important reason for P450s activity inhibition. The effect of silybin throughout the whole course suggested that it regulated P450s activity through its anti-ER stress effect in NAFLD. Our results suggest that ER stress may be crucial for the inhibition of P450s activity in mouse NAFLD and silybin regulates P450s activity by attenuating ER stress.

The Effects of Hydro-Priming and Colonization with Piriformospora indica and Azotobacter chroococcum on Physio-Biochemical Traits, Flavonolignans and Fatty Acids Composition of Milk Thistle (Silybum marianum) under Saline Conditions.[Pubmed:35631705]

Plants (Basel). 2022 May 10;11(10). pii: plants11101281.

Salinity is an important challenge around the world, effecting all physiological and biochemical processes of plants. It seems that seed priming can diminish the negative impacts of salinity. To study the effects of hydro-priming and inoculation with Piriformospora indica (Pi) and Azotobacter chroococcum (Az) on physio-biochemical traits, flavonolignans and fatty acids composition of milk thistle under saline conditions, a greenhouse experiment was carried out. Our results indicated that under salinity, seed priming, especially Pi, improved physio-biochemical properties in milk thistle. Under 120 mM NaCl, inoculation with Pi increased membrane stability index (MSI) and relative water content (RWC) (by 21.86 and 33.43%, respectively). However, peroxidase (POX) (5.57- and 5.68-fold in roots and leaves, respectively), superoxide dismutase (SOD) (4.74- and 4.44-fold in roots and leaves, respectively), catalase (CAT) (6.90- and 8.50-fold in roots and leaves, respectively) and ascorbate peroxidase (APX) (5.61- and 5.68-fold in roots and leaves, respectively) activities increased with increasing salinity. Contrary to salinity, hydro-priming with Az and Pi positively altered all these traits. The highest content of the osmolytes, adenosine triphosphate (ATP) content and rubisco activity were recorded in Pi treatments under 120 mM NaCl. Stearic acid (20.24%), oleic acid (21.06%) and palmitic acid (10.48%) increased, but oil content (3.81%), linolenic and linoleic acid content (22.21 and 15.07%, respectively) decreased under saline conditions. Inoculations of Pi positively altered all these traits. The present study indicated that seed priming with Pi under 120 mM NaCl resulted in maximum silychristin, taxidolin, silydianin, isosilybin, Silybin And silymarin of milk thistle seeds.

Potential antimicrobial, antidiabetic, catalytic, antioxidant and ROS/RNS inhibitory activities of Silybum marianum mediated biosynthesized copper oxide nanoparticles.[Pubmed:35558860]

RSC Adv. 2022 May 11;12(22):14069-14083.

Use of medicinal plants for the biosynthesis of nanoparticles offers several advantages over other synthesis approaches. Plants contain a variety of bioactive compounds that can participate in reduction and capping of nanoparticles. Plant mediated synthesis has the leverage of cost effectiveness, eco-friendly approach and sustained availability. In the current study Silybum marianum, a medicinally valuable plant rich in silymarin content, is used as a reducing and stabilizing agent for the fabrication of nanoparticles. Biosynthesized CuO-NPs were characterized using High Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS) techniques. Characterization revealed that CuO-NPs having a crystalline structure showed spherical morphology with an average size of 15 nm. HPLC analysis demonstrated conjugation of various silymarin components, especially the presence of Silybin A (705.06 +/- 1.59 mg g(-1) DW). CuO-NPs exhibited strong bactericidal potency against clinically important pathogenic bacterial strains e.g. Enterobacter aerogenes and Salmonella typhi with an inhibition zone of 18 +/- 1.3 mm and 17 +/- 1.2 mm, respectively. Synthesized nanoparticles indicated a dose dependent cytotoxic effect against fibroblast cells exhibiting a percentage cell viability of 83.60 +/- 1.505% and 55.1 +/- 1.80% at 25 mug mL(-1) and 100 mug mL(-1) concentration, respectively. Moreover, CuO-NPs displayed higher antioxidant potential in terms of (TAC: 96.9 +/- 0.26 mug AAE/mg), (TRP: 68.8 +/- 0.35 mug AAE/mg), (DPPH: 55.5 +/- 0.62%), (ABTS: 332.34 muM) and a significant value for (FRAP: 215.40 muM). Furthermore, enzyme inhibition assays also exhibited excellent enzyme inhibition potential against alpha-amylase (35.5 +/- 1.54%), urease (78.4 +/- 1.26%) and lipase (80.50.91%), respectively. Overall findings indicated that biosynthesized CuO-NPs possess immense in vitro biological and biomedical properties and could be used as a broad-spectrum agent for a wider range of biomedical applications.

Silybin and its congeners: from traditional medicine to molecular effects.[Pubmed:35510639]

Nat Prod Rep. 2022 Jun 22;39(6):1264-1281.

Covering: 2015 up to 2022 (Feb)Silymarin, an extract of milk thistle (Silybum marianum) fruits, has been used in various medicinal applications since ancient times. A major component of silymarin is the flavonolignan Silybin And its relatives isosilybin, silychristin, silydianin, 2,3-dehydrosilybin, and some others. Except for silydianin, they occur in nature as two stereomers. This review focuses on recent developments in chemistry, biosynthesis, modern advanced analytical methods, and transformations of flavonolignans specifically reflecting their chirality. Recently described chemotypes of S. marianum, but also the newest findings regarding the pharmacokinetics, hepatoprotective, antiviral, neuroprotective, and cardioprotective activity, modulation of endocrine functions, modulation of multidrug resistance, and safety of flavonolignans are discussed. A growing number of studies show that the respective diastereomers of flavonolignans have significantly different activities in anisotropic biological systems. Moreover, it is now clear that flavonolignans do not act as antioxidants in vivo, but as specific ligands of biological targets and therefore their chirality is crucial. Many controversies often arise, mainly due to the non-standard composition of this phytopreparation, the use of various undefined mixtures, the misattribution of silymarin vs. silybin, and also the failure to consider the chemistry of the respective components of silymarin.