Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells

Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl4). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl4-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

International journal of molecular sciences - 22(2021), 24 vom: 12. Dez.

Sprache:

Englisch

Beteiligte Personen:

Kataoka, Seita [VerfasserIn]
Umemura, Atsushi [VerfasserIn]
Okuda, Keiichiro [VerfasserIn]
Taketani, Hiroyoshi [VerfasserIn]
Seko, Yuya [VerfasserIn]
Nishikawa, Taichiro [VerfasserIn]
Yamaguchi, Kanji [VerfasserIn]
Moriguchi, Michihisa [VerfasserIn]
Kanbara, Yoshihiro [VerfasserIn]
Arbiser, Jack L [VerfasserIn]
Shima, Toshihide [VerfasserIn]
Okanoue, Takeshi [VerfasserIn]
Itoh, Yoshito [VerfasserIn]

Links:

Volltext

Themen:

11513CCO0N
Autophagy
Biphenyl Compounds
Hepatic fibrosis
Honokiol
Journal Article
Lignans
Smad Proteins
Stellate cell
Tgfb1 protein, mouse
Transforming Growth Factor beta1

Anmerkungen:

Date Completed 10.01.2022

Date Revised 10.01.2022

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms222413354

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334840589