Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives

Viktorová, Jitka; Dobiasová, Simona; Řehořová, Kateřina; Biedermann, David; Káňová, Kristýna; Šeborová, Karolína; Václavíková, Radka; Valentová, Kateřina; Ruml, Tomáš; Křen, Vladimı́r; Macek, Tomáš

doi:10.3390/antiox8080303

Cited by 27 publications

(33 citation statements)

References 54 publications

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“…As described in our previous study [23], the resistance of the A2780/DOX cell line is connected to the over-expression of several ABC genes, especially ABCB1 (P-gp) and ABCC1 (MRP1). Therefore, the modulation of P-gp could be caused by inhibition of ATPase activity or by regulation of its expression.…”

Section: Discussionmentioning

confidence: 63%

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Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

et al. 2020

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Silybin is considered to be the main biologically active component of silymarin. Its oxidized derivative 2,3-dehydrosilybin typically occurs in silymarin in small, but non-negligible amounts (up to 3%). Here, we investigated in detail complex biological activities of silybin and 2,3-dehydrosilybin optical isomers. Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, as well as their racemic mixtures, were investigated by using oxygen radical absorption capacity (ORAC) and cellular antioxidant activity (CAA) assay. All substances efficiently reduced nitric oxide production and cytokines (TNF-α, IL-6) release in a dose-dependent manner. Multidrug resistance (MDR) modulating potential was evaluated as inhibition of P-glycoprotein (P-gp) ATPase activity and regulation of ATP-binding cassette (ABC) protein expression. All the tested compounds showed strong dose-dependent inhibition of P-gp pump. Moreover, 2,3-dehydrosilybin A (30 µM) displayed the strongest sensitization of doxorubicin-resistant ovarian carcinoma. Despite these significant effects, silybin B was the only compound acting directly upon P-gp in vitro and also downregulating the expression of respective MDR genes. This compound altered the expression of P-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). 2,3-Dehydrosilybin AB exhibited the most effective inhibition of acetylcholinesterase activity. We can clearly postulate that silybin derivatives could serve well as modulators of a cancer drug-resistant phenotype.

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Section: Discussionmentioning

confidence: 63%

“…Additionally, treatment of an ovarian carcinoma cell line (A2780/DPP) resistant to cisplatin and taxol with 50 µM silybin enhanced sensitivity of the cells to both drugs [22]. We have recently published modulation of P-gp expression by other flavonolignans, such as 2,3-dehydrosilychristin and anhydrosilychristin [23].…”

Section: Introductionmentioning

confidence: 99%

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

et al. 2020

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“…P-glycoprotein (P-gp), which is also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family member B 1 (ABCB1), is an ATP-dependent efflux pump transporting a wide range of hydrophobic compounds including drugs and other xenobiotics [79]. It limits the drug entry into the body, promotes drugs elimination into bile and urine, and decreases drug penetration into sensitive tissues [80].…”

Section: P-gp Substrate Probability Of Single Mycotoxinsmentioning

confidence: 99%

“…The in vitro P-gp activation was tested using the Pgp-Glo Assay System according to the standard procedure [79]. Briefly, the reaction mixture contained Pgp-Glo Assay buffer, P-gp containing membranes, and MgATP in a total volume of 50 µL.…”

Section: P-gp Substrate Determinationmentioning

confidence: 99%

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Tran

Viktorová

Augustynkova

et al. 2020

Toxins

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Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.

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“…Each inhibitory activity was measured in four replicates. The sensitization of drug-resistant bacteria was realized according to [36].…”

Section: Inhibition Of Multidrug-resistant Bacterial Strainsmentioning

confidence: 99%

Antimicrobial Activity of Extracts of Two Native Fruits of Chile: Arrayan (Luma apiculata) and Peumo (Cryptocarya alba)

et al. 2020

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Arrayan and peumo fruits are commonly used in the traditional medicine of Chile. In this study, the concentration of the extracts halving the bacterial viability and biofilms formation and disruption of the drug-sensitive and drug-resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa was determined. The chemical composition of extracts was analyzed by high-resolution liquid chromatography coupled with mass spectrometry (U-HPLC/MS). The arrayan extract (Inhibitory concentration IC50 0.35 ± 0.01 mg/mL) was more effective than peumo extract (IC50 0.53 ± 0.02 mg/mL) in the inhibition of S. aureus planktonic cells. Similarly, the arrayan extract was more effective in inhibiting the adhesion (S. aureus IC50 0.23 ± 0.02 mg/mL, P. aeruginosa IC50 0.29 ± 0.02 mg/mL) than peumo extracts (S. aureus IC50 0.47 ± 0.03 mg/mL, P. aeruginosa IC50 0.35 ± 0.01 mg/mL). Both extracts inhibited quorum sensing in a concentration-dependent manner, and the most significant was the autoinducer-2 type communication inhibition by arrayan extract. Both extracts also disrupted preformed biofilm of P. aeruginosa (arrayan IC50 0.56 ± 0.04 mg/mL, peumo IC50 0.59 ± 0.04 mg/mL). However, neither arrayan nor peumo extracts disrupted S. aureus mature biofilm. U-HPLC/MS showed that both fruit extracts mainly possessed quercetin compounds; the peumo fruit extract also contained phenolic acids and phenylpropanoids. Our results suggested that both extracts could be used as natural antimicrobials for some skin and nosocomial infections.

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Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives

Cited by 27 publications

References 54 publications

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Antimicrobial Activity of Extracts of Two Native Fruits of Chile: Arrayan (Luma apiculata) and Peumo (Cryptocarya alba)

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