Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor

Abstract

Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility.

Tanshinone IIA Protects Endothelial Cells from H2O2-Induced Injuries via PXR Activation

“…Tan IIA, a pharmacologically active component of the Chinese herb Danshen, has been shown to possess various effects on cardiovascular diseases, and some of these actions are due to its anti-oxidative stress, anti-apoptotic, and anti-inflammatory properties ( Shu et al ., 2016 ). Among these, in our previous studies we have demonstrated that Tan IIA exerts protective effects in cholestatic liver and inflammatory bowel disease that are associated with the activation of the pregnane X receptor in vivo and vitro , these studies indicated that as an agonist of PXR, Tan IIA can have a variety of pharmacological effects via the activation of PXR ( Zhang et al ., 2015a , 2015b ). In the present study, we examined the effects of Tan IIA on cultured HUVECs injured by H 2 O 2 ( Fig.…”

“…Tanshinone IIA (Tan IIA), the major component extracted from Radix Salvia miltiorrhiza, is also known as the Chinese herb danshen ( Su et al ., 2016 ), and is widely used for treating cerebral and cardiovascular diseases such as atherosclerosis, stroke, coronary heart disease, and hyperlipidemia ( Zhang et al ., 2015b ). In our previous studies show Tan IIA exerts protective effects in cholestatic liver model and inflammatory bowel disease that are associated with the participation of the PXR in vivo and vitro .…”

Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating CYP2J3/EETs in Rats

“…Pregnane X receptor (PXR) is an important transcriptional regulator of CYP2 enzymes and transporters in cardiovascular therapy [47,48]. Previously, we have found that many Chinese medicine monomers mediate protection against several diseases via activating PXR [49][50][51], and that OP-D induces PXR nuclear translocation. Therefore, we hypothesize that OP-D has an effect on CYP2J2/3 through PXR activation.…”

Activation of PXR by Alpinetin Contributes to Abrogate Chemically Induced Inflammatory Bowel Disease

“…Induction of Cyp3a4 and Mdr1 contributes to the metabolism of approximately 50% of clinically used drugs and a large amount of xenobiotics (Mani et al, 2013). Gene expression analysis has indicated significant downregulation of PXR and its target genes in the colon of IBD patients (Zhang X. et al, 2015). Downregulation of Cyp3a and Mdr1 was also observed in the intestine of DSS-treated mice (Kawauchi et al, 2014).…”