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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F20%3A43921269" target="_blank" >RIV/60461373:22330/20:43921269 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/20:00532776 RIV/75010330:_____/20:00012995 RIV/00216208:11140/20:10411186

Result on the web

<a href="https://www.mdpi.com/2076-3921/9/5/455" target="_blank" >https://www.mdpi.com/2076-3921/9/5/455</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/antiox9050455" target="_blank" >10.3390/antiox9050455</a>

Result language

angličtina

Original language name

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

Original language description

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-alpha, 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 mu M) 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Antioxidants

ISSN

2076-3921

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

5

Country of publishing house

CH - SWITZERLAND

Number of pages

22

Pages from-to

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UT code for WoS article

000539284200098

EID of the result in the Scopus database

2-s2.0-85086412954