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Phenylethanol Glycosides from Cistanche tubulosa Suppress Hepatic Stellate Cell Activation and Block the Conduction of Signaling Pathways in TGF-?1/smad as Potential Anti-Hepatic Fibrosis Agents.

ABSTRACT: Cistanche tubulosa is a traditional Chinese herbal medicine widely used for regulating immunity and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. Previous studies have indicated the preventive and therapeutic effects of CPhGs on bovine serum albumin (BSA)-induced hepatic fibrosis in rats. The aim of the study was to evaluate the anti-hepatic fibrosis effect of CPhGs and the monomers echinacoside and acteoside by inhibiting hepatic stellate cell (HSC) activation, blocking the conduction of signaling pathways in transforming growth factor-?1 (TGF-?1)/smad, and determine their in vitro hepatoprotective activity. HSC proliferation was obviously inhibited after treatment with CPhGs (100, 50 ?g/mL)/echinacoside (500, 250, 125 ?g/mL)/acteoside (6, 3 ?g/mL), with IC50 values of 119.125, 520.345 and 6.999 ?g/mL, respectively, in the MTT assay. Different concentrations of CPhGs/echinacoside/acteoside did not affect the cellular toxicity on HSC according to lactate dehydrogenase (LDH) measurements. Different concentrations of CPhGs/echinacoside/acteoside increased the mRNA level and protein expression of smad7, and decreased the mRNA levels of smad2, smad3 and the protein expression of smad2, phospho-smad2 (p-smad2), smad3, phospho-smad3 (p-smad3) in HSC. In summary, these results demonstrate that CPhGs/echinacoside/acteoside can block the conduction of the signaling pathways in TGF-?1/smad, and inhibit the activation of HSC, suggesting that C. tubulosa may thus be a potential herbal medicine for the treatment of liver fibrosis.

SUBMITTER: You SP

PROVIDER: S-EPMC6273390 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Phenylethanol Glycosides from Cistanche tubulosa Suppress Hepatic Stellate Cell Activation and Block the Conduction of Signaling Pathways in TGF-β1/smad as Potential Anti-Hepatic Fibrosis Agents.

You Shu-Ping SP Ma Long L Zhao Jun J Zhang Shi-Lei SL Liu Tao T

Molecules (Basel, Switzerland) 20160118 1

Cistanche tubulosa is a traditional Chinese herbal medicine widely used for regulating immunity and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. Previous studies have indicated the preventive and therapeutic effects of CPhGs on bovine serum albumin (BSA)-induced hepatic fibrosis in rats. The aim of the study was to evaluate the anti-hepatic fibrosis effect of CPhGs and the monomers echinacoside and acteoside by inhibiting hepatic stellate cell ...[more]

PMID: 26797590

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Project description:BackgroundCistanche tubulosa is a traditional Chinese herbal medicine that is widely used for regulating immunity. Phenyl ethanol glycosides (CPhGs) from this plant are the primarily efficacious materials. This aim of this study was to evaluate the preventive and therapeutic effects of CPhGs on BSA-induced hepatic fibrosis in rats and related molecular mechanisms involving hepatic stellate cells. Biejiarangan (BJRG), another traditional Chinese herbal medicine, was used as a positive control.MethodsIn in vivo experiments, 75 SD rats were randomly divided into 6 groups: normal (distilled water-treated), model (BSA-treated), positive drug (BSA-treated?+?BJRG 600 mg/kg/day), and BSA-treated?+?CPhGs (125, 250, and 500 mg/kg/day) groups. The liver and spleen indices, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), type III procollagen (PCIII), type IV collagen (IV-C), hydroxyproline (Hyp), and transforming growth factor ? 1 (TGF-? 1) were measured in rat livers. Histopathological grades for liver fibrosis were assessed for each group using H&E and Masson's trichrome staining. The expression of TGF-? 1, collagen I (Col-I) and collagen III (Col-III) were determined by an immunohistochemical staining method. These effects were further evaluated in vitro by determining expression levels of NF-?B p65 and Col-I by quantitative real-time PCR analyses. Col-I protein expression was also examined by western blotting.ResultsAll dose groups (125, 250, and 500 mg/kg/day) of CPhGs significantly reduced the liver and spleen index, decreased ALT, AST, HA, LN, PCIII, IV-C serum levels, TGF-? 1 content (P?<?0.01, P?<?0.01, and P?<?0.01), and Hyp content. CPhGs also markedly alleviated the swelling of liver cells and effectively prevented hepatocyte necrosis and inflammatory cell infiltration. Immunohistochemical results showed that CPhGs significantly reduced the expression of TGF-? 1 (P?<?0.01, P?<?0.01, and P?<?0.01), Col- I, and Col-III. The in vitro effects of CPhGs (100, 75, 50, and 25 ug/ml) on HSC-T6 showed that CPhGs significantly reduced mRNA expression of NF-?B p65 and Col-I, and CPhGs also downregulated Col-I protein expression.ConclusionsCPhGs have a significant anti-hepatic fibrosis effect, and may be used as hepatoprotective agents for treatment of hepatic fibrosis.

Dataset Information

Phenylethanol Glycosides from Cistanche tubulosa Suppress Hepatic Stellate Cell Activation and Block the Conduction of Signaling Pathways in TGF-?1/smad as Potential Anti-Hepatic Fibrosis Agents.

Publications

Phenylethanol Glycosides from Cistanche tubulosa Suppress Hepatic Stellate Cell Activation and Block the Conduction of Signaling Pathways in TGF-β1/smad as Potential Anti-Hepatic Fibrosis Agents.

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