title: SHSST-cyclodextrin complex inhibits TGF-β/Smad3/CTGF to a greater extent than silymarin in a rat model of carbon tetrachloride-induced liver injury.
abstract: At present, cirrhosis is an incurable liver disease. Transforming growth factor β (TGF‑β) is important in myofibroblast induction during the cirrhosis initiation process. The current approach in the development of hepatoprotective drugs depends on TGF‑β inhibition. San Huang Shel Shin Tang (SHSST) is a traditional herbal decoction able to exert a protective effect on the liver, however, similar to silymarin, it is limited by its hydrophobicity. In the present study, SHSST was modified with β‑cyclodextrin to form a hydrophilic complex, which improved its bioavailability. In the carbon tetrachloride‑induced acute injury animal model, the effects of pretreatment with silymarin, baicalein, SHSST and the SHSST‑β‑CD‑complex (SHSSTc) at a low and high dose were assessed. The biopsy results revealed marked liver protection following treatment with silymarin, baicalein and SHSST and these effects were improved further following pretreatment with SHSSTc. Protein analysis demonstrated that the hepatoprotective effects of silymarin occurred through inhibition of the TGF‑β/Smad‑3/connective tissue growth factor (CTGF) signaling pathway. SHSSTc exerted the same protective mechanism, however, SHSSTc suppressed CTGF level to a greater extent compared with the groups treated with SHSST or silymarin. Only pretreatment with SHSST and SHSSTc exhibited partial enhancement in the expression of proteins involved in the regulation of liver regeneration, including extracellular‑signal‑regulated kinase 5, phospho‑nuclear factor of activated T cells 3 and phospho‑GATA4.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Ting
authors.affiliation: Department of Nursing, Meiho University, Pingtung 91202, Taiwan, R.O.C.
authors.forename: Chia-Yao
authors.initials: CY
authors.lastname: Shen
authors.affiliation: Division of Colorectal Surgery, Mackay Memorial Hospital, New Taipei 10449, Taiwan, R.O.C.
authors.forename: His-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C.
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Department of Laboratory, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou 54249, Taiwan, R.O.C.
authors.forename: Sheng-Huang
authors.initials: SH
authors.lastname: Chang
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore 641046, India.
authors.forename: Viswanadha Vijaya
authors.initials: VV
authors.lastname: Padma
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D012838:Silymarin / Q000494:pharmacology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; D003505:Cyclodextrins; D044950:Flavanones; D015850:Interleukin-6; D020011:Protective Agents; D012838:Silymarin; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C006680:baicalein; D002251:Carbon Tetrachloride