Tanshinol ameliorates CCl₄-induced liver fibrosis in rats through the regulation of Nrf2/HO-1 and NF-κB/IκBα signaling pathway

Abstract

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.

Tanshinol A Ameliorates Triton‐1339W‐Induced Hyperlipidemia and Liver Injury in C57BL/6J Mice by Regulating mRNA Expression of Lipemic‐Oxidative Injury Genes

“…Taken together of tanshinol A‐changing phenotype (pathological observation, reduced MDA, and improvement in liver injury) and genotype (restorement in Aft4 , Fgf21 , Angplt4 and Vldlr ), hepatic injury alleviation, and hopylipidemic effect of tanshinol A are possibly associated with scavenge of triton‐1339W‐lead cellular stress through simultaneously mediating Vldlr transcriptional promotion and Aft4 ‐involved pathways. Therefore, a major mechanism of tanshinol A alleviating liver injury is partially consensus with previous research in terms of regulating Aft4 ‐involved pathway (Wang et al, ) and enhancing capacity of antioxidation (Yang et al, ), and it is first time that hopylipidemic mechanisms of tanshinol A are found to be highly associated with upregulation of Atf4/Fgf21/Vldlr . Still, there are some tanshinol A‐leading mRNA expression alteration such as Angptl4 and Fgf21 , which are fasting‐induced adipose factor (Gonzalez‐Muniesa et al, ) and pathogenesis of hepatic steatosis (Zarei et al, ), respectively, do not show consensus to previous research, and this inconsistency may be characteristic pathogenesis for triton‐1339W‐induced hyperlipidemia and liver injury, and it is reversible after tanshinol A treatment.…”

“…Moreover, it possesses multiply pharmacological functions i.e. protecting hepatocyte toward CCl 4 ‐induced liver injury (Wang et al, ), protecting endothelial cells against homocysteine‐induced injury (Chen et al, ; Song et al, ), and lowering methionine‐induced hyperhomocysteinemia (Tian et al, ) in rats. An increasing body of evidence shows that tanshinol A can improve health by mediating endogenous metabolism such as lipid metabolism, and thereby therapeutic effect and regulative mechanism of tanshinol A treating hyperlipidemia is worth further exploring.…”

Retracted: Tanshinol relieves lipopolysaccharide‐induced inflammatory injury of HaCaT cells via down‐regulation of microRNA‐122

“…(Lamiaceae; Y. Yang et al, ). Previous studies demonstrated that TAN exerted anti‐inflammatory and protective effects on vascular dementia and liver fibrosis (Wang et al, ; Y. Yang et al, ). In consistent with the previous studies, we revealed that TAN treatment alleviated the LPS‐induced HaCaT cell viability loss, apoptosis, and up‐regulation of Cox‐2 and iNOS expression, which indicated that TAN also could exert anti‐inflammatory and protective effects on pressure ulcers.…”

“…In terms of anti‐inflammatory activity, Y. Yang et al () reported that TAN inhibited inflammatory response in a rat model of vascular dementia. Wang, Wang, Song, Li, and Yuan () pointed out that TAN ameliorated carbon tetrachloride (CCl 4 )‐induced up‐regulation of transforming growth factor‐β, tumor necrosis factor‐α, cyclooxygenase 2 (Cox‐2), interleukin‐1β (IL‐1β), and IL‐6 expression in the serum of rats. However, there is no any information available about the effects of TAN on skin keratinocytes inflammatory injury in pressure ulcers.…”

Tanshinol inhibits the growth, migration and invasion of hepatocellular carcinoma cells via regulating the PI3K-AKT signaling pathway

“…Currently, it is frequently used in herbal medicine for its anti-inflammatory activity, anti-arthritic properties, wound and burn healing capabilities, and anti-bacterial/anti-cancer properties 11–15. There are several biologically active constituents in S. miltiorrhiza , including tanshinol 16–18. Previous investigation has demonstrated that tanshinol regulates adhesion molecule expression of tumor necrosis factor alpha (TNF-α)-induced endothelial cells by blocking activation of nuclear factor kappa B (NF-κB) 19.…”