Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-inflammatory Potential.
P-glycoprotein
acetylcholinesterase inhibition
cytokines
dehydrosilybin
doxorubicin resistance
expression profile
immunomodulation
silybin
Journal
Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981
Informations de publication
Date de publication:
25 May 2020
25 May 2020
Historique:
received:
20
04
2020
revised:
18
05
2020
accepted:
21
05
2020
entrez:
30
5
2020
pubmed:
30
5
2020
medline:
30
5
2020
Statut:
epublish
Résumé
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,
Identifiants
pubmed: 32466263
pii: antiox9050455
doi: 10.3390/antiox9050455
pmc: PMC7278776
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Grantová Agentura České Republiky
ID : 18-00150S
Organisme : Czech National Program of Sustainability
ID : LO1601 (MSMT-43760/2015)
Organisme : Ministerstvo Školství, Mládeže a Tělovýchovy
ID : INTER-COST LTC19007 and LTC19020
Déclaration de conflit d'intérêts
small lung carcinoma resistant to etoposide, doxorubicin and vincristine
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