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 <i>Magnolia grandiflora<...
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13354 |
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| author | Seita Kataoka Atsushi Umemura Keiichiro Okuda Hiroyoshi Taketani Yuya Seko Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Yoshihiro Kanbara Jack L. Arbiser Toshihide Shima Takeshi Okanoue Yoshito Itoh |
| author_facet | Seita Kataoka Atsushi Umemura Keiichiro Okuda Hiroyoshi Taketani Yuya Seko Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Yoshihiro Kanbara Jack L. Arbiser Toshihide Shima Takeshi Okanoue Yoshito Itoh |
| author_sort | Seita Kataoka |
| collection | DOAJ |
| description | 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 <i>Magnolia grandiflora</i>, 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 (CCl<sub>4</sub>). 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 CCl<sub>4</sub>-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. |
| first_indexed | 2024-03-10T03:56:37Z |
| format | Article |
| id | doaj.art-6d1de62a58cf4b15a1d6e4a2f0dbe52e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:56:37Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6d1de62a58cf4b15a1d6e4a2f0dbe52e2023-11-23T08:45:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241335410.3390/ijms222413354Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate CellsSeita Kataoka0Atsushi Umemura1Keiichiro Okuda2Hiroyoshi Taketani3Yuya Seko4Taichiro Nishikawa5Kanji Yamaguchi6Michihisa Moriguchi7Yoshihiro Kanbara8Jack L. Arbiser9Toshihide Shima10Takeshi Okanoue11Yoshito Itoh12Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanDepartment of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 564-0013, JapanDepartment of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 564-0013, JapanDepartment of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita 564-0013, JapanMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, JapanChronic 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 <i>Magnolia grandiflora</i>, 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 (CCl<sub>4</sub>). 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 CCl<sub>4</sub>-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.https://www.mdpi.com/1422-0067/22/24/13354hepatic fibrosisstellate cellhonokiolautophagy |
| spellingShingle | Seita Kataoka Atsushi Umemura Keiichiro Okuda Hiroyoshi Taketani Yuya Seko Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Yoshihiro Kanbara Jack L. Arbiser Toshihide Shima Takeshi Okanoue Yoshito Itoh Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells International Journal of Molecular Sciences hepatic fibrosis stellate cell honokiol autophagy |
| title | Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells |
| title_full | Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells |
| title_fullStr | Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells |
| title_full_unstemmed | Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells |
| title_short | Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells |
| title_sort | honokiol acts as a potent anti fibrotic agent in the liver through inhibition of tgf β1 smad signaling and autophagy in hepatic stellate cells |
| topic | hepatic fibrosis stellate cell honokiol autophagy |
| url | https://www.mdpi.com/1422-0067/22/24/13354 |
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