PMID- 32193805 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20200727 IS - 1861-0293 (Electronic) IS - 1340-3443 (Linking) VI - 74 IP - 3 DP - 2020 Jun TI - The effects of inhibiting the activation of hepatic stellate cells by lignan components from the fruits of Schisandra chinensis and the mechanism of schisanhenol. PG - 513-524 LID - 10.1007/s11418-020-01394-w [doi] AB - Liver fibrosis is a pathological manifestation induced by chronic liver injury and may cause cirrhosis and liver cancer with the chronic progression of fibrosis. During the onset and progression of liver fibrosis, the activation of hepatic stellate cells (HSCs) is the core mechanism for the secretion of many extracellular matrices to induce fibrosis. Lignans are reportedly the main effective components of Schisandra chinensis with good anti-fibrosis effects. In this study, we compared the inhibiting effects of the seven lignan components from S. chinensis on HSC activation. We found that the seven lignans inhibited the activation of human HSCs (LX-2) in various degrees. Among all lignans, schisanhenol showed the best effect in inhibiting the activation of LX-2 with a dose-effect relationship. Sal also inhibited the phosphorylations of Smad1, Smad2, Smad3, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and nuclear transcription factor-kappaB (NF-kappaB), as well as downregulated Smad4. All these findings suggested that schisanhenol may ameliorate liver fibrosis by inhibiting the transforming growth factor beta (TGF-beta)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. Remarkably, schisanhenol may be a potential anti-liver fibrosis drug and warrants further research. FAU - He, Xiaoli AU - He X AUID- ORCID: 0000-0002-4519-3550 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. AD - TCM Department, Ningbo Huamei Hospital Affiliated to Chinese Academy of Sciences, 41 Xibei Road, Ningbo, 315010, China. FAU - Chen, Jiamei AU - Chen J AUID- ORCID: 0000-0001-9808-9610 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. FAU - Mu, Yongping AU - Mu Y AUID- ORCID: 0000-0002-4533-5563 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. FAU - Zhang, Hua AU - Zhang H AUID- ORCID: 0000-0001-5926-0999 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. FAU - Chen, Gaofeng AU - Chen G AUID- ORCID: 0000-0001-9617-8003 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. FAU - Liu, Ping AU - Liu P AUID- ORCID: 0000-0002-6152-4508 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. liuliver@vip.sina.com. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. liuliver@vip.sina.com. FAU - Liu, Wei AU - Liu W AUID- ORCID: 0000-0002-7284-0936 AD - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China. lwhzayl@163.com. AD - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai, 201203, China. lwhzayl@163.com. LA - eng GR - 81530101/National Natural Science Foundation of China/ GR - 81703681/National Natural Science Foundation of China/ PT - Journal Article DEP - 20200319 PL - Japan TA - J Nat Med JT - Journal of natural medicines JID - 101518405 RN - 0 (Cyclooctanes) RN - 0 (Lignans) RN - 0 (NF-kappa B) RN - 0 (Polycyclic Compounds) RN - 0 (SMAD1 protein, human) RN - 0 (SMAD2 protein, human) RN - 0 (SMAD3 protein, human) RN - 0 (Smad1 Protein) RN - 0 (Smad2 Protein) RN - 0 (Smad3 Protein) RN - 0 (Transforming Growth Factor beta) RN - 80Y5907NIW (schisanhenol) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cell Line MH - Cyclooctanes/*pharmacology MH - Fruit/chemistry MH - Hepatic Stellate Cells/drug effects/*metabolism MH - Humans MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Lignans/*pharmacology MH - Liver Cirrhosis/pathology/*prevention & control MH - NF-kappa B/metabolism MH - Polycyclic Compounds/*pharmacology MH - Schisandra/*chemistry MH - Signal Transduction/drug effects MH - Smad1 Protein/metabolism MH - Smad2 Protein/metabolism MH - Smad3 Protein/metabolism MH - Transforming Growth Factor beta/antagonists & inhibitors MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - Human hepatic stellate cell (LX-2) OT - Lignans OT - MAPK signaling pathway OT - Schisandra chinensis OT - Schisanhenol OT - TGF-beta/Smad signaling pathway EDAT- 2020/03/21 06:00 MHDA- 2020/07/28 06:00 CRDT- 2020/03/21 06:00 PHST- 2019/10/04 00:00 [received] PHST- 2020/03/06 00:00 [accepted] PHST- 2020/03/21 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2020/03/21 06:00 [entrez] AID - 10.1007/s11418-020-01394-w [pii] AID - 10.1007/s11418-020-01394-w [doi] PST - ppublish SO - J Nat Med. 2020 Jun;74(3):513-524. doi: 10.1007/s11418-020-01394-w. Epub 2020 Mar 19.