Protective effects of dioscin against doxorubicin-induced nephrotoxicity via adjusting FXR-mediated oxidative stress and inflammation

Zhang, Yimeng; Xu, Youwei; Qi, Yan; Xu, Lina; Song, Shasha; Yin, Lianhong; Tao, Xufeng; Zhen, Yuhong; Han, Xu; Ma, Xiaodong; Liu, Kexin; Peng, Jinyong

doi:10.1016/j.tox.2017.01.007

Cited by 125 publications

(80 citation statements)

References 50 publications

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“…S6A to C ). Recent studies demonstrate the interactions between the FXR signaling pathway and Nrf2-mediated antioxidant effects 33 , 34 . Therefore, we examined whether the protective effects of FXR activation and the induction of antioxidant genes were mediated through Nrf2.…”

Section: Resultsmentioning

confidence: 99%

Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage

Gai

Chu

et al. 2017

Sci Rep

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Farnesoid X receptor (FXR) activation has been reported to reduce inflammation and oxidative stress. Because both inflammation and oxidative stress are critical for tissue destruction during kidney ischemia reperfusion (I/R) injury, we investigated the protective role of FXR against kidney damage induced by I/R in mice. Mice undergoing renal I/R developed the typical features of acute kidney injury (AKI): increased creatinine, albuminuria, tubular necrosis and apoptosis. Inflammatory cytokine production and oxidative stress were also markedly increased. In mice pretreated with 6-ethyl-chenodeoxycholic acid (6-ECDCA), a selective FXR agonist, I/R induced changes were prevented and renal function and structure were improved. Moreover, FXR activation also effectively prevented the subsequent progression of AKI to chronic kidney disease (CKD) by ameliorating glomerulosclerosis and interstitial fibrosis and by suppressing fibrogenic gene expression. FXR mRNA levels were inversely correlated with the progression to CKD in mice and with the degree of interstitial fibrosis in human biopsies. In further experiments administering 6-ECDCA to renal proximal tubular cells cultured under hypoxia, the renoprotective effects of FXR activation were associated with inhibition of oxidative and ER stress and with increased antioxidant activity. In conclusion, FXR agonists may have a therapeutic role in conditions associated with ischemic kidney damage.

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Section: Resultsmentioning

confidence: 99%

Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage

Gai

Chu

et al. 2017

Sci Rep

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“…It has previously been reported that activation of Sirt1 decreased the production of several pro-inflammatory cytokines, including TNF-a, IL-12, and IL-18 in EIC rats and protected syncytiotrophoblasts against TCA-induced inflammatory injury through the Sirt1-NF-kB signaling pathway (Liao et al, 2018). Moreover, NF-kB is a downstream gene of FXR, and upregulating Sirt1/FXR/NF-kB signaling had an efficient protective effect on rats from hemorrhagic shock induced liver injury by decreasing inflammatory responses (Zhang et al, 2017;Sun et al, 2019;Yu et al, 2019). Thus, we hypothesized that activation of FXR by baicalin through the Sirt1/HNF-1a signaling pathway might also play a key role in regulating the NF-kB pathway, which would need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, FXR is one of the most important BA sensors in maintaining BA homeostasis through regulating BA synthesis, metabolism, and transport (Kuipers et al, 2004). It has also been shown that activation of FXR exerts anti-inflammatory effects in liver diseases (Zhang et al, 2017). However, FXR does not work alone (Kemper et al, 2009;Li et al, 2017) and is regulated by multiple signaling pathways (Zhang et al, 2004;Li et al, 2016;Yang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

Yang

Xiang

et al. 2020

Front. Pharmacol.

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Estrogen-induced cholestasis (EIC) is characterized by impairment of bile flow and accumulated bile acids (BAs) in the liver, always along with the liver damage. Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in EIC remains to be elucidated. In this study, we demonstrated that baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum biomarkers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic BAs. In addition, baicalin protected against estrogen-induced liver injury by up-regulation of the expression of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat, Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-a, IL-1b, IL-6, and NF-kB. Finally, we confirmed that baicalin maintains hepatic BA homeostasis and alleviates inflammation through sirtuin 1 (Sirt1)/hepatic nuclear receptor-1a (HNF-1a)/ farnesoid X receptor (FXR) signaling pathway. Thus, baicalin protects against estrogeninduced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1a/FXR signaling pathway.

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“…Otherwise, FXR activation occurred in high-fat diet (HFD) fed mice with increased proinflammatory leukotrienes B4 (LTB4) and lower (3-fold) anti-inflammatory epoxyeicosatrienoic acids (EETs) [223]. FXR induced inflammation can be suppressed by the novel FXR-agonist, dioscin, with consequent suppression of NF-jB and High mobility group box 1 protein (HMGB-1), and subsequently decreased the mRNA levels of IL-b1, IL-6, and TNFa [224].…”

Section: Barrett's Reflux and Bile Acidmentioning

confidence: 99%

NF-κB signaling and crosstalk during carcinogenesis

Brücher

Läng

Jamall

2019

4open

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Transcription factors (TFs) are proteins that control the transcription of genetic information from DNA to mRNA by binding to specific DNA sequences either on their own or with other proteins as a complex. TFs thus support or suppress the recruitment of the corresponding RNA polymerase. In general, TFs are classified by structure or function. The TF, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), is expressed in all cell types and tissues. NF-κB signaling and crosstalk are involved in several steps of carcinogenesis including in sequences involving pathogenic stimulus, chronic inflammation, fibrosis, establishment of its remodeling to the precancerous niche (PCN) and transition of a normal cell to a cancer cell. Triggered by various inflammatory cytokines, NF-κB is activated along with other TFs with subsequent stimulation of cell proliferation and inhibition of apoptosis. The involvement of NF-κB in carcinogenesis provides an opportunity to develop anti-NF-κB therapies. The complexity of these interactions requires that we elucidate those aspects of NF-κB interactions that play a role in carcinogenesis, the sequence of events leading to cancer.

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Protective effects of dioscin against doxorubicin-induced nephrotoxicity via adjusting FXR-mediated oxidative stress and inflammation

Cited by 125 publications

References 50 publications

Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage

Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage

Baicalin Protects Against 17α-Ethinylestradiol-Induced Cholestasis via the Sirtuin 1/Hepatic Nuclear Receptor-1α/Farnesoid X Receptor Pathway

NF-κB signaling and crosstalk during carcinogenesis

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