Tanshinone IIA attenuates acetaminophen-induced hepatotoxicity through HOTAIR-Nrf2-MRP2/4 signaling pathway

Tanshinone IIA Prevents Acetaminophen-Induced Nephrotoxicity by Stimulating the Efflux of its Toxic Intermediate Metabolite From Kidney

“…Similar ndings were reported in our previous study indicating that Nrf2-MRPs pathway play a vital role in preventing APAPinduced hepatotoxicity (Zhang et al, 2020). Furthermore, we have performed the luciferase reporter assays and chromatin immunoprecipitation assays to investigate how Nrf2 acts on MRP2 and MRP4, and the results of two assays indicated that Nrf2 could increase MRP2 and MRP4 promoter activity by binding to the certain AREs in MRP2 and MRP4 promoter, thus forming the Nrf2-MRPs signaling pathway (Zhang et al, 2020). The ndings of RNA interference experiment and mRNA/protein expression research on Nrf2-MRPs in this study were in agreement with the previous claim.…”

“…Tan IIA performed a protective effect against liver injury caused by APAP through increasing Nrf2 and its target detoxi cation enzyme genes (Wang et al, 2016). Similar ndings were reported in our previous study indicating that Nrf2-MRPs pathway play a vital role in preventing APAPinduced hepatotoxicity (Zhang et al, 2020). Furthermore, we have performed the luciferase reporter assays and chromatin immunoprecipitation assays to investigate how Nrf2 acts on MRP2 and MRP4, and the results of two assays indicated that Nrf2 could increase MRP2 and MRP4 promoter activity by binding to the certain AREs in MRP2 and MRP4 promoter, thus forming the Nrf2-MRPs signaling pathway (Zhang et al, 2020).…”

“…Therefore, we performed a pharmacokinetic study to investigate the effects of Tan IIA on the pharmacokinetic pro les of APAP and its metabolites in mice. As reported in our previous study, after pretreatment of Tan IIA, t 1/2 and V z of APAP in mice were signi cantly lower than those in control group, indicating that Tan IIA enhanced the elimination and affected the distribution of APAP in vivo (Zhang et al, 2020). As illustrated in Fig.…”

“…Recent studies have reported that Tan IIA alleviates APAP-induced hepatotoxicity and contrast-induced nephropathy by enhancing the expression of anti-oxidative proteins, such as GCLC, NQO1 and HO-1 (Liang et al, 2018;Wang et al, 2016), which is largely in uenced by the regulation of nuclear factor E2-related factor 2 (Nrf2). Our previous study has demonstrated that Tan IIA could protect against APAP-induced hepatotoxicity through the HOTAIR-Nrf2-MRPs pathway (Zhang et al, 2020). However, the effects of Tan IIA in APAP-induced nephrotoxicity have not been investigated, and if Nrf2 plays a role in this pharmacodynamic effect remains unknown.…”

Hypoxia-Inducible Factor-1: A Potential Target to Treat Acute Lung Injury

“…Danshen is a common herbal medicine that has been used clinically in China and many other Asian countries to prevent or control cardiovascular diseases [153]. Tanshinone IIA (TIIA), a derivative of phenanthrenequinone and one of the key components of Danshen, has been reported to have immunoregulatory, anti-inflammatory, and antioxidative properties [154,155]. TIIA can alleviate lipopolysaccharide-induced ALI by inhibiting HIF-1α [156].…”