PMID- 33668543
OWN - NLM
STAT- MEDLINE
DCOM- 20210415
LR  - 20210415
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 13
TI  - Complexation with Random Methyl-beta-Cyclodextrin and 
      (2-Hidroxypropyl)-beta-Cyclodextrin Enhances In Vivo Anti-Fibrotic and 
      Anti-Inflammatory Effects of Chrysin via the Inhibition of NF-kappaB and TGF-beta1/Smad 
      Signaling Pathways and Modulation of Hepatic Pro/Anti-Fibrotic miRNA.
LID - 10.3390/ijms22041869 [doi]
LID - 1869
AB  - Chrysin (CHR) is a natural flavonoid with a wide range of pharmacological 
      activities, including hepatoprotection, but poor water solubility. By including 
      water-soluble hydroxypropyl (HPBCD) and randomly methylated (RAMEB) 
      beta-cyclodextrin, we aimed to increase its biodisponibility and the effectiveness 
      of the antifibrotic effects of chrysin at oral administration. Liver fibrosis in 
      mice was induced in 7 weeks by CCl(4) i.p. administration, and afterwards treated 
      with 50 mg/kg of CHR-HPBCD, CHR-RAMEB, and free chrysin. CCl(4) administration 
      increased hepatic inflammation (which was augmented by the upregulation of 
      nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumor 
      necrosis factor (TNF)-alpha, and interleukin 6 (IL-6) and induced fibrosis, as 
      determined using histopathology and electron microscopy. These results were also 
      confirmed by the upregulation of Collagen I (Col I) and matrix metalloproteinase 
      (MMP) expression, which led to extracellular fibrotic matrix proliferation. 
      Moreover, the immunopositivity of alpha-smooth muscle actin (a-SMA) in the CCl(4) 
      group was evidence of hepatic stellate cell (HSC) activation. The main 
      profibrotic pathway was activated, as confirmed by an increase in the 
      transforming growth factor- beta1 (TGF-beta1) and Smad 2/3 expression, while Smad 7 
      expression was decreased. Treatment with CHR-HPBCD and CHR-RAMEB considerably 
      reduced liver injury, attenuated inflammation, and decreased extracellular liver 
      collagen deposits. CHR-RAMEB was determined to be the most active antifibrotic 
      complex. We conclude that both nanocomplexes exert anti-inflammatory effects and 
      antifibrotic effects in a considerably stronger manner than for free chrysin 
      administration.
FAU - Ciceu, Alina
AU  - Ciceu A
AUID- ORCID: 0000-0001-6502-2655
AD  - "Aurel Ardelean" Institute of Life Sciences, "Vasile Goldis" Western University 
      of Arad, 86 Revolution Str., 310048 Arad, Romania.
AD  - Department of Biochemistry and Molecular Biology, Faculty of Biology, University 
      of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.
FAU - Balta, Cornel
AU  - Balta C
AD  - "Aurel Ardelean" Institute of Life Sciences, "Vasile Goldis" Western University 
      of Arad, 86 Revolution Str., 310048 Arad, Romania.
FAU - Herman, Hidegard
AU  - Herman H
AUID- ORCID: 0000-0002-6741-0245
AD  - "Aurel Ardelean" Institute of Life Sciences, "Vasile Goldis" Western University 
      of Arad, 86 Revolution Str., 310048 Arad, Romania.
FAU - Gharbia, Sami
AU  - Gharbia S
AD  - "Aurel Ardelean" Institute of Life Sciences, "Vasile Goldis" Western University 
      of Arad, 86 Revolution Str., 310048 Arad, Romania.
FAU - Ignat, Simona-Rebeca
AU  - Ignat SR
AUID- ORCID: 0000-0002-9752-6927
AD  - Department of Biochemistry and Molecular Biology, Faculty of Biology, University 
      of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.
FAU - Dinescu, Sorina
AU  - Dinescu S
AUID- ORCID: 0000-0001-7196-1712
AD  - Department of Biochemistry and Molecular Biology, Faculty of Biology, University 
      of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.
AD  - Research Institute of the University of Bucharest, Splaiul Independentei 91-95, 
      050095 Bucharest, Romania.
FAU - Varadi, Judit
AU  - Varadi J
AD  - Department of Pharmaceutical Technology, Faculty of Pharmacy, University of 
      Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
FAU - Fenyvesi, Ferenc
AU  - Fenyvesi F
AUID- ORCID: 0000-0003-2890-0783
AD  - Department of Pharmaceutical Technology, Faculty of Pharmacy, University of 
      Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
FAU - Gyongyosi, Szilvia
AU  - Gyongyosi S
AD  - Department of Solid State Physics, University of Debrecen, P.O. Box 400, H-4002 
      Debrecen, Hungary.
FAU - Hermenean, Anca
AU  - Hermenean A
AUID- ORCID: 0000-0001-8510-6653
AD  - "Aurel Ardelean" Institute of Life Sciences, "Vasile Goldis" Western University 
      of Arad, 86 Revolution Str., 310048 Arad, Romania.
AD  - Department of Histology, Faculty of Medicine, Vasile Goldis Western University of 
      Arad, 86 Revolution Str., 310414 Arad, Romania.
FAU - Costache, Marieta
AU  - Costache M
AUID- ORCID: 0000-0002-8103-3693
AD  - Department of Biochemistry and Molecular Biology, Faculty of Biology, University 
      of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.
LA  - eng
GR  - PN-III-P2-2.1-PED2019-3609 (262PED/2020)/Romanian Ministry of Research and 
      Innovation/
PT  - Journal Article
DEP - 20210213
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Flavonoids)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (Smad Proteins)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (beta-Cyclodextrins)
RN  - 0 (methyl-beta-cyclodextrin)
RN  - 3CN01F5ZJ5 (chrysin)
SB  - IM
MH  - Animals
MH  - Flavonoids/*pharmacology
MH  - *Liver Cirrhosis/drug therapy/genetics/metabolism/pathology
MH  - Male
MH  - Mice
MH  - MicroRNAs/*biosynthesis/genetics
MH  - NF-kappa B/genetics/*metabolism
MH  - Signal Transduction/*drug effects/genetics
MH  - Smad Proteins/genetics/*metabolism
MH  - Transforming Growth Factor beta1/genetics/*metabolism
MH  - beta-Cyclodextrins/*pharmacology
PMC - PMC7917810
OTO - NOTNLM
OT  - HPBCD
OT  - RAMEB
OT  - chrysin
OT  - fibrosis
OT  - inflammation
OT  - liver
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/16 06:00
PMCR- 2021/02/13
CRDT- 2021/03/06 01:02
PHST- 2021/01/02 00:00 [received]
PHST- 2021/01/24 00:00 [revised]
PHST- 2021/02/08 00:00 [accepted]
PHST- 2021/03/06 01:02 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/16 06:00 [medline]
PHST- 2021/02/13 00:00 [pmc-release]
AID - ijms22041869 [pii]
AID - ijms-22-01869 [pii]
AID - 10.3390/ijms22041869 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 13;22(4):1869. doi: 10.3390/ijms22041869.