Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via regulating TLR4/MyD88 signal pathway

Yao, Hong; Hu, Changsheng; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Qi, Yan; Han, Xu; Xu, Youwei; Zhao, Yanyan; Wang, Changyuan; Peng, Jinyong

doi:10.1016/j.intimp.2016.04.023

Cited by 78 publications

(52 citation statements)

References 45 publications

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“…Pharmacological studies have demonstrated that this natural product shows active effects against cancer (Hsieh et al, 2013), hyperlipidemic (Li et al, 2010) and fungus (Li et al, 2003). In previous works, we found that dioscin had good effects against liver fibrosis (Liu et al, 2015; Zhang et al, 2015), acute liver damages (Lu et al, 2012; Yao et al, 2016), obesity (Liu et al, 2015), osteoporosis (Tao et al, 2016), renal and hepatic ischemia/reperfusion injury (Tao et al, 2014; Qi et al, 2015). Importantly, dioscin has active effect against α- naphthylisothiocyanate (ANIT)-induced liver cholestasis (Zhang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Dioscin Protects ANIT-Induced Intrahepatic Cholestasis Through Regulating Transporters, Apoptosis and Oxidative Stress

Yao

Yin

et al. 2017

Front. Pharmacol.

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Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment. The results showed that dioscin markedly altered relative liver weights, restored ALT, AST, ALP, TBIL, GSH, GSH-Px, MDA, SOD levels, and rehabilitated ROS level and cell apoptosis. In mechanism study, dioscin not only significantly regulated the protein levels of Ntcp, OAT1, OCT1, Bsep and Mrp2 to accelerate bile acids excretion, but also regulated the expression levels of Bak, Bcl-xl, Bcl-2, Bax, Caspase 3 and Caspase 9 in vivo and in vitro to improve apoptosis. In addition, dioscin markedly inhibited PI3K/Akt pathway and up-regulated the levels of Nrf2, GCLc, GCLm, NQO1 and HO-1 against oxidative stress (OS) caused by bile acids. These results were further validated by inhibition of PI3K and Akt using the inhibitors of wortmannin and perifosine in SCHs. Our data showed that dioscin had good action against ANIT-caused intrahepatic cholestasis through regulating transporters, apoptosis and OS. This natural product can be considered as one active compound to treat intrahepatic cholestasis in the future.

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Section: Introductionmentioning

confidence: 99%

Dioscin Protects ANIT-Induced Intrahepatic Cholestasis Through Regulating Transporters, Apoptosis and Oxidative Stress

Yao

Yin

et al. 2017

Front. Pharmacol.

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“…In our previous study, we have reported that dioscin has significant effects on l LPS-induced liver injury (Yao et al, 2016), LPS-induced kidney injury (Qi et al, 2016), non-alcoholic fatty liver disease (NAFLD) (Xu et al, 2014), hepatic ischemia- reperfusion damage (Tao et al, 2014), and hepatic fibrosis (Zhang et al, 2015). In our knowledge, dioscin has played significant roles on liver (Zhang et al, 2015; Yao et al, 2016), kidney (Qi et al, 2016), bone (Tao et al, 2016), and brain (Tao X.F.…”

Section: Introductionmentioning

confidence: 99%

“…In our knowledge, dioscin has played significant roles on liver (Zhang et al, 2015; Yao et al, 2016), kidney (Qi et al, 2016), bone (Tao et al, 2016), and brain (Tao X.F. et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Dioscin against Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Oxidative Stress and Inflammation

et al. 2017

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The protective effects of dioscin, a natural steroidal saponin from some medicinal plants including Dioscorea nipponica Makino, against lipopolysaccharide (LPS)-induced acute liver and renal damages have been reported in our previous works. However, the actions of dioscin against LPS-induced acute lung injury (ALI) is still unknown. In the present study, we investigated the effects and mechanisms of dioscin against LPS-induced ALI in vitro and in vivo. The results showed that dioscin obviously inhibited cell proliferation and markedly decreased reactive oxidative species level in 16HBE cells treated by LPS. In addition, dioscin significantly protected LPS-induced histological changes, inhibited the infiltration of inflammatory cells, as well as decreased the levels of MDA, SOD, NO and iNOS in mice and rats (p < 0.05). Mechanistically, dioscin significantly decreased the protein levels of TLR4, MyD88, TRAF6, TKB1, TRAF3, phosphorylation levels of PI3K, Akt, IκBα, NF-κB, and the mRNA levels of IL-1β, IL-6, and TNF-α against oxidative stress and inflammation (p < 0.05). Dioscin significantly reduced the overexpression of TLR4, and obviously down-regulated the levels of MyD88, TRAF6, TKB1, TRAF3, p-PI3K, p-Akt, p-IκBα, and p-NF-κB. These findings provide new perspectives for the study of ALI. Dioscin has protective effects on LPS-induced ALI via adjusting TLR4/MyD88-mediated oxidative stress and inflammation, which should be a potent drug in the treatment of ALI.

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“…Once in the extracellular space, HMGB-1 exerts its biological functions via interaction with its receptors, including receptor for advanced glycation end products (RAGE) [21,22], TLR2 [23][24][25][26], TLR4 [27][28][29][30], and TLR9 [31]. The interaction between HMGB-1 and its receptors has been shown to induce cell adhesion [32], permeability [33,34], chemotaxis [35], inflammation [36][37][38], autophagy [39][40][41], apoptosis [42][43][44], thrombosis [16,45,46], angiogenesis [47,48], fibrosis [49,50], and epithelialmesenchymal transition (EMT) [51,52].…”

Section: Figmentioning

confidence: 99%

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

Pei

et al. 2018

Cell Physiol Biochem

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High mobility group box-1 (HMGB-1), a typical damage-associated molecular pattern protein released from various cells, was first identified in 1973. It is usually stored in the nuclei of cells. Several modifications of HMGB-1 promote its translocation to the cytosol, and it is actively or passively released from cells. When outside of the cells, HMGB-1is crucial in inflammation. It exerts its biological functions via interaction with its receptors, including receptor for advanced glycation end products (RAGE) and Toll-like receptor 4(TLR4). A large number of studies showed a close link between inflammation and thrombosis. This review demonstrated the increased expression of HMGB-1 in thrombosis-related diseases, including coronary artery disease, stroke, peripheral arterial disease, disseminated intravascular coagulation, and venous thrombosis. Besides, it summarized the current understanding of the emerging link between HMGB-1 and thrombosis from three aspects: platelet, NETs, and coagulation and fibrinolysis factors. Finally, it explored the possible therapeutic strategies targeting HMGB-1 for treating thrombosis-related diseases.

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Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via regulating TLR4/MyD88 signal pathway

Cited by 78 publications

References 45 publications

Dioscin Protects ANIT-Induced Intrahepatic Cholestasis Through Regulating Transporters, Apoptosis and Oxidative Stress

Dioscin Protects ANIT-Induced Intrahepatic Cholestasis Through Regulating Transporters, Apoptosis and Oxidative Stress

Protective Effects of Dioscin against Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Oxidative Stress and Inflammation

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

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