Dataset Information

Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.

ABSTRACT:

Background

Anti-inflammation via inhibition of NF-?B pathways in hepatic stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA) is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.

Materials and methods

The cell line of rat hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100 ng/ml). Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM), then induced by LPS (100 ng/ml). NF-?B activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-?B-p65, and phosphorylations of MAPKs (ERK, JNK, p38). Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.

Results

All concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-?B luciferase activities, nuclear translocation of NF-?B-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1?, TNF-?, IL-6, ICAM-1, iNOS, and ?-SMA in HSC-T6 cells.

Conclusion

Our results demonstrated that Tan IIA decreased LPS-induced HSC activation.

SUBMITTER: Liu YW

PROVIDER: S-EPMC4116159 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.

Liu Ya-Wei YW Huang Yi-Tsau YT

PloS one 20140730 7

<h4>Background</h4>Anti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs) is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA) is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.<h4>Materials and methods</h4>The cell line of rat hepatic stellate cells (HSC-T6) was stimulated with lipopolysaccharide (LPS) (100 ng/ml). Cytotoxi ...[more]

PMID: 25076488

Similar Datasets

Project description:Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut-brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation.

Dataset Information

Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.

Background

Materials and methods

Results

Conclusion

Publications

Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets