SHSST cyclodextrin complex prevents the fibrosis effect on CCl₄-induced cirrhotic cardiomyopathy in rats through TGF-β pathway inhibition effects

SHSST环糊精复合物通过TGF-β通路抑制作用预防CCl₄诱发的大鼠肝硬化性心肌病的纤维化作用

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作者:Cheng-Hsun Yang, Wei-Jen Ting, Cecilia Hsuan Day, Da-Tong Ju, Yu-Lan Yeh, Li-Chin Chung, Fu-Jenn Tsai, Chang-Hai Tsai, Yuhsin Tsai, Chih-Yang Huang

Abstract

Patients with liver cirrhosis also have subtle cardiac structure or function abnormalities. This cardiac dysfunction commonly occurs in 56% of waiting orthotopic liver transplantation (OLT) patients and is defined as cirrhotic cardiomyopathy (CCM). Up to now, there is no standard treatment because CCM does not have a solidly established diagnosis and is based on high clinical suspicion. The liver function of CCM is particularly limited, making patients vulnerable to more drug treatments. Here, we use silymarin (100 mg/kg/day), baicalein (30 mg/kg/day), San Huang Shel Shin Tang (SHSST, 30 mg/kg/day) and β-cyclodextrin modified SHSST (SHSSTc, 30 and 300 mg/kg/day) treatments for a CCl4-induced CCM rat model. The results show that silymarin, baicalein and SHSST treatments can only slightly reduce the collagen accumulation in CCM rat hearts. However, SHSSTc treatment protects the heart in CCM and significantly inhibits collagen acumination and the fibrosis regulating transforming growth factor-β (TGF-β) pathway expression. SHSSTc treatments further reduced the heart weight and the ratio between left ventricular weight (LVW) and tibia length (TL). This experimental data show that water solubility improved β-cyclodextrin modified Chinese herbal medicine formula (SHSSTc) can provide an excellent heart protection effect through TGF-β pathway inhibition.

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