Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosis

Hsu, Yi‐Chao; Chiu, Yung-Tsung; Cheng, Ching-Chang; Wu, Ching-Fen; Lin, Yun‐Lian; Huang, Yi-Tsau

doi:10.1111/j.1440-1746.2006.04361.x

Cited by 77 publications

(80 citation statements)

References 67 publications

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“…Silymarin also inhibited TNF-α induced activation of MAPK and JNK, TNF-induced cytotoxicity and caspase activation. Silymarin in combination with tetrandrine attenuates NF-κB activated pathways and the induction of metallothionein gene transcription in the liver of dimethylnitrosamine (DMN) administered rats [20]. In human mesangial cells, silymarin showed dose dependent inhibition of TNF-α-and IL-1β-induced NF-κB activation, and TNF-α-induced intracellular calcium and MCP-1 expression [21].…”

Section: Anti-inflammatory Effects Of Silymarinmentioning

confidence: 99%

Multitargeted therapy of cancer by silymarin

2008

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Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to estabilished therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. This review focuses on the chemistry and analogues of silymarin, multiple possible molecular mechanisms, in vitro as well as in vivo anticancer activities, and studies on human clinical trials.

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Section: Anti-inflammatory Effects Of Silymarinmentioning

confidence: 99%

Multitargeted therapy of cancer by silymarin

2008

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“…The pictures of FITC images and those of rhodamine images were merged using Leica image analysis software. Double staining techniques of α-SMA and NFκB p65 were adapted from the report of Kitamura and Ninomiya (2003) and have been established in our laboratory (Chong et al, 2006;Hsu et al, 2007). The method for counting the numbers of α-smooth muscle actin (α-SMA) and NFκB-positive staining was adapted from Parsons et al (2004).…”

Section: Introductionmentioning

confidence: 99%

“…Quantitative PCR analysis was performed using an ABI prism 7900 HT Sequence Detection System (Applied Biosystems, Foster City, CA, USA). In the study, two different methods of quantitative PCR were used (Chong et al, 2006;Hsu et al, 2007): (I) SyBR Green method for the expression of G3PDH, ICAM-1, TGF-β1 and α-SMA genes. SyBR Green, a double-stranded DNA binding dye, was used for the fluorescent detection of DNA generated during the PCR.…”

Section: Introductionmentioning

confidence: 99%

Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats

Lin

Hsu²,

Chiu

et al. 2007

Phytotherapy Research

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Liver fibrosis has been characterized as chronic inflammatory processes involving multiple molecular pathogenetic pathways. This therapeutic study investigated whether a combination regimen of Salvia miltiorrhiza (S), Ligusticum chuanxiong (L) and Glycyrrhiza glabra (G) exerted in vivo antifibrotic effects on rats with hepatic fibrosis. Fibrosis was induced in rats by dimethylnitrosamine (DMN) administration for 4 weeks. Fibrotic rats were randomly assigned to one of the three groups: control, SLG (50 mg/kg) or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting 1 week after DMN injection. The results showed that fibrosis scores of livers from DMN-treated rats with SLG (1.13 ± ± ± ± ± 0.13) were significantly reduced in comparison with DMN-treated rats receiving vehicle (1.63 ± ± ± ± ± 0.18). Moreover, the hepatic collagen content of DMN rats was significantly reduced by either SLG or silymarin treatment. The double immunohistochemical staining results also showed that α α α α α-SMA positive cells with NFκ κ κ κ κB nuclear translocation were decreased in the fibrotic livers by SLG and silymarin treatments. The mRNA expression levels of TGF-β β β β β 1, α α α α α -SMA, collagen1α α α α α2, iNOS and ICAM-1 genes were attenuated by SLG and silymarin treatment. The results showed that SLG exerted antifibrotic effects in rats with DMN-induced hepatic fibrosis.

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“…Tetrandrine significantly reduced Iκα expression and TNF-α induced NF-κB activity, Iκα phosphorylation and NF-κB nuclear translocation in HSC-T6 cells, reduced the NF-κB activity stimulated by tumor necrosis factor-α (TNF-α) and hydrogen peroxide in HSC-T6 cells, and also reduced the mRNA expression of the NF-κB responsive gene, intra cellular adhesion molecule-1, induced by TNF-α, tetrandrine concentration dependently attenuated TGF-β1 stimulated α-SMA secretion and collagen deposition in HSC-T6 cells [43] . Along this line Lee et al reported tetrandrine treatment prevented liver fibrosis in bile duct ligated rats by suppressing the expression of TIMP-I mRNA of HSCs in fibrogenesis, resulting in reduced expression of collagen lead to promotion of matrix degradation [44] .…”

Section: Tetrandrinementioning

confidence: 99%