Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition

Tao, Xufeng; Sun, Xiance; Yin, Lianhong; Han, Xu; Xu, Lina; Qi, Yan; Xu, Youwei; Li, Hua; Lin, Yuan; Liu, Kexin; Peng, Jinyong

doi:10.1016/j.freeradbiomed.2015.03.003

Cited by 128 publications

(86 citation statements)

References 44 publications

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“…Thus, after administration of CCl 4 , it was firstly catalyzed by CYP2E1 to generate reactive oxygen species CCl 3 * and CCl 3 OO*, which triggered TLR4/MyD88, and further activated key transcription factor NF-κB by degrading cytosolic IκB-α, leading to the transcription of the pro-inflammatory mediators such as TNF-α and IL-1β. Tao25 reported that Dioscin exerted its anti-inflammatory properties via the reduction of the expression levels TLR4 level and downstream proteins including MyD88, MAPKs, NF-κB, and AP-1 in dose dependent test, which meant that both MAPKs and TLR4/NF-κB pathways contributed to the development of the inflammation in this system25. Nevertheless, in our system, MAPKs-mediated pathway mainly participated in caspase-9 phosphorylation to induce hepato-protective autophagy.…”

Section: Discussionmentioning

confidence: 63%

Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

Guo

Lin

Pan

et al. 2016

Sci Rep

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Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.

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Section: Discussionmentioning

confidence: 63%

Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

Guo

Lin

Pan

et al. 2016

Sci Rep

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“…Suppression the release of HMGB-1 directly inhibited the activation of TLR4/MyD88/NFkB signalling pathway in neuron, suggesting that HMGB-1 could induce proinflammatory cytokines via the TLR4-dependent pathway [41]. TLR4 knockout (KO) or pharmacologic inhibition of TLR4 can attenuate the inflammatory response and neuronal apoptosis in response to cerebral I/RI [42,43].…”

Section: Discussionmentioning

confidence: 99%

Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

Zhang

Fan

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: A combination of alpha-lipoic acid preconditioning (ALAP) and ischaemic preconditioning (IPC) has not been tested in an in vivo rat cerebral ischaemia/reperfusion injury (I/RI) model, and the potential protective mechanisms have not been well elucidated. The aim of this study was to investigate the role of the TLR4/ MyD88/ NF-κB signaling pathway in the synergistically neuroprotective and anti-inflammatory effects of ALAP and IPC. Methods: One hundred and fifty male Sprague-Dawley rats, weighing 180-230 g, were randomly divided into the following 5 groups: 1) sham-operated control; 2) I/R; 3) I/R+ALAP; 4) I/R+IPC; 5) I/R+IPC+ALAP. After 2 h of reperfusion, the infarct size, neurological deficit scores, brain oedema, oxidative stress, and inflammatory and apoptotic biomarkers were assessed. In addition, reactive oxygen species (ROS) and cell apoptosis were detected by DHE staining and TUNEL staining, respectively. Results: Both ALAP and IPC treatment attenuated the I/RI-induced neuronal injury, reflected by reductions in the infarct size, neurological deficit scores, brain oedema, lactate dehydrogenase (LDH) release and the inflammatory response, as well as decreased HMGB1, TLR4, MyD88, p65, C-Caspase 3 and Bax expression and increased IKB-α, HO-1, SOD-2 and Bcl-2 expression compared to that in the I/R group. Furthermore, the combination of the two strategies had synergistic anti-inflammatory effects and antioxidant benefits, ultimately limiting neuronal apoptosis. Conclusion: The ‘cocktail’ strategy exhibited a significant neuroprotection against I/RI by attenuating neuroinflammation via inhibition of the TLR4/MyD88/NF-κB signaling pathway.

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“…More and more evidence revealed the important role of TLR4-mediated signaling pathway in inflammation. Recently, it was shown that HMGB 1/TLR4 signaling contributed to inflammation in hepatic ischemia/reperfusion injury [44]. However, Mudaliar et al suggested TLR4 as an important mediator for inflammation in high glucose-induced endothelial cells [45].…”

Section: Discussionmentioning

confidence: 99%

Reduced HMGB 1‐Mediated Pathway and Oxidative Stress in Resveratrol‐Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus

Sheng

Xie

et al. 2016

Oxidative Medicine and Cellular Longevity

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Myocardial fibrosis and inflammation are intricately linked in diabetic cardiomyopathy (DCM), and resveratrol has been shown to attenuate oxidative stress, inflammation, and fibrosis in several cell types or animal models. High mobility group box 1 (HMGB 1), a proinflammatory cytokine, has been reported to regulate fibrosis and inflammation in various organs. Then the present study aimed to reveal the expression of HMGB 1-mediated signaling pathway and oxidative stress in resveratrol-treated diabetic mice. The significant increase in serum HMGB 1 concentration in diabetic mice was attenuated by treatment with resveratrol. Similarly, western blot analysis revealed a significant increase of HMGB 1 protein in monocytes and heart tissues of diabetic mice, and resveratrol partly normalized the changes. In addition, resveratrol abrogated the increased expression of HMGB 1-mediated signaling pathway, oxidative stress, fibrosis, and inflammation in diabetic hearts. In conclusion, inhibition of HMGB 1-mediated signaling pathway and oxidative stress may contribute to resveratrol-induced anti-inflammatory and antifibrotic effects in DCM.

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Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition

Cited by 128 publications

References 44 publications

Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

Alpha-Lipoic Acid Preconditioning and Ischaemic Postconditioning Synergistically Protect Rats from Cerebral Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/ NF-κB Signaling Pathway

Reduced HMGB 1‐Mediated Pathway and Oxidative Stress in Resveratrol‐Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus

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