Tanshinol ameliorates CCl4-induced liver fibrosis in rats through the regulation of Nrf2/HO-1 and NF-κB/IκBα signaling pathway
| Autor: | Fuxing Song, Yongfang Yuan, Jing Wang, Shengnan Li, Rong Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmacology chemistry.chemical_classification biology Glutathione peroxidase Pharmaceutical Science CCL4 Malondialdehyde medicine.disease_cause Salvia miltiorrhiza Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound IκBα 030104 developmental biology 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Drug Discovery biology.protein medicine Tumor necrosis factor alpha Oxidative stress |
| Zdroj: | Drug Design, Development and Therapy. 12:1281-1292 |
| ISSN: | 1177-8881 |
| Popis: | Tanshinol, a water-soluble component isolated from Salvia miltiorrhiza Bunge, has a variety of biological activities involving anti-fibrotic effect. However, the exact role and the underlying mechanisms remain largely unclear. This study mainly focused on the anti-hepatic fibrotic activities and mechanisms of tanshinol on carbon tetrachloride (CCl4)-induced liver fibrosis in rats via anti-oxidative and anti-inflammation pathways. The rats were divided into 4 groups as follows: control, model, tanshinol 20 mg/kg, and tanshinol 40 mg/kg. Except for the control group, CCl4 was used to induce liver fibrosis processing for 8 weeks, meanwhile rats in tanshinol groups were intraperitoneally injected with additional tanshinol. Control group simultaneously received the same volumes of olive oil and saline. The potentially protective effect and mechanisms of tanshinol on liver fibrosis in rats were evaluated. The serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were obviously lower in the tanshinol treatment groups related to model group. Compared with the model group, the levels of hyaluronic acid, type IV collagen, Laminin (LN), and procollagen III peptide (PIIIP) in serum were significantly decreased after tanshinol treatment. Furthermore, tanshinol could regulate Nrf2/HO-1 signaling pathway and increase the level of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and also decrease the level of malondialdehyde (MDA) to against damage induced by oxidative stress. Simultaneously tanshinol could regulate nuclear factor kappa B signaling pathway to inhibit expression of inflammation factors, including transforming growth factor-β, tumor necrosis factor-α, Cox-2, interleukin-1β, and interleukin-6. In summary, our research demonstrated that tanshinol has protective effect on CCl4-induced liver fibrosis via inhibiting oxidative stress and inflammation, which may be associated with the regulation of nuclear factor erythroid2-related factor 2/hemeoxygenase-a and nuclear factor kappa B/inhibitor of kappa B alpha signaling pathways. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|