Protective effects of dendropanoxide isolated from Dendropanax morbifera against cisplatin-induced acute kidney injury via the AMPK/mTOR signaling pathway

Ischemic stroke is one of the major causes of disability; widely use of endovascular thrombectomy or intravenous thrombolysis leads to more attention on ischemia-reperfusion injury (I/R injury). Aescin, a natural compound isolated from the seed of the horse chestnut, has been demonstrated anti-inflammatory and antiedematous effects previously. This study was aimed at determining whether aescin could induce protective effects against ischemia-reperfusion injury and exploring the underlying mechanisms in vitro. Primary cultured neurons were subjected to 2 hours of oxygen-glucose deprivation (OGD) followed by 24 hours of simulated reperfusion. Aescin, which worked in a dose-dependent manner, could significantly attenuate neuronal death and reduce lactate dehydrogenase (LDH) release after OGD and simulated reperfusion. Aescin treatment at a concentration of 50 μg/ml provided protection with fewer side effects. Results showed that aescin upregulated the phosphorylation level of PRAS40 and proteins in the mTOR signaling pathway, including S6K and 4E-BP1. However, PRAS40 knockdown or rapamycin treatment was able to undermine and even abolish the protective effects of aescin; meanwhile, the levels of phosphorylation PRAS40 and proteins in the mTOR signaling pathway were obviously decreased. Hence, our study demonstrated that aescin provided neuronal protective effects against I/R injury through the PRAS40/mTOR signaling pathway in vitro. These results might contribute to the potential clinical application of aescin and provide a therapeutic target on subsequent cerebral I/R injury.

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Pancreas protective effects of Urolithin A on type 2 diabetic mice induced by high fat and streptozotocin via regulating autophagy and AKT/mTOR signaling pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2019.112479 ◽

2020 ◽

Vol 250 ◽

pp. 112479 ◽

Cited By ~ 1

Author(s):

Bahetibieke Tuohetaerbaike ◽

Yan Zhang ◽

Yali Tian ◽

Nan nan Zhang ◽

Jinsen Kang ◽

...

Keyword(s):

Signaling Pathway ◽

Mtor Signaling ◽

Protective Effects ◽

Diabetic Mice ◽

Mtor Signaling Pathway ◽

High Fat ◽

Urolithin A ◽

Type 2 Diabetic

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Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signaling pathway

10.22541/au.163546444.48023459/v1 ◽

2021 ◽

Author(s):

Jianqiang HU ◽

Wenjing Gu ◽

Ning Ma ◽

Xiaoye Fan ◽

Xinxin Ci

Keyword(s):

Lipid Peroxidation ◽

Acute Kidney Injury ◽

Signaling Pathway ◽

Lipid Peroxide ◽

Kidney Injury ◽

Iron Accumulation ◽

Protective Effects ◽

Nrf2 Signaling Pathway

Background and purpose: Increasing evidence suggests that ferroptosis plays a key role in the pathophysiology of acute kidney injury induced by cisplatin. The Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation and positively regulates cisplatin-induced AKI (CI-AKI). However, Nrf2 and its activator leonurine on ferroptosis after CI-AKI remain unclear. Experimental Approach: The anti-ferroptotic effects of Nrf2 and its activator leonurine were assessed using a mouse model of cisplatin-induced AKI. In vitro, the potential effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined. Key Results: As expected, Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, further aggravating CI-AKI. The Nrf2 activator leonurine prevented iron accumulation and lipid peroxidation and inhibited ferroptosis in vitro, while these effects were abolished in siNrf2-treated cells. Moreover, leonurine potently ameliorated cisplatin-induced renal damage, as indicated by the assessment of SCr, BUN, KIM-1, and NGAL. Importantly, leonurine activated the Nrf2 antioxidative signaling pathway and prohibited changes in ferroptosis-related morphological and biochemical indicators, such as the MDA level, SOD and GSH depletion and GPX4 and xCT downregulation, in CI-AKI. Moreover, Nrf2 KO mice were more susceptible to ferroptosis after CI-AKI than control mice, and the protective effects of leonurine on AKI and ferroptosis were largely abolished in Nrf2 KO mice. Conclusion and Implications: These data suggest that the renal protective effects of Nrf2 and its activator leonurine on CI-AKI are achieved at least partially by inhibiting lipid peroxide-mediated ferroptosis and highlight the potential of leonurine as a CI-AKI treatment.

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Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.706251 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhen Qi ◽

Renrong Wang ◽

Rongheng Liao ◽

Song Xue ◽

Yongyi Wang

Keyword(s):

Signaling Pathway ◽

Cardiac Dysfunction ◽

Myocardial Dysfunction ◽

Heart Tissue ◽

Mtor Signaling ◽

Mouse Heart ◽

Septic Cardiomyopathy ◽

Protective Effects ◽

H9c2 Cells ◽

Mtor Signaling Pathway

Septic cardiomyopathy is a common complication of severe sepsis, which is one of the leading causes of death in intensive care units. Therefore, finding an effective therapy target is urgent. Neferine is an alkaloid extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., which has been reported to exhibit various biological activities and pharmacological properties. This study aims to explore the protective effects of neferine against lipopolysaccharide (LPS)-induced myocardial dysfunction and its mechanisms. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of neferine. In this study, we demonstrated that neferine remarkably improved cardiac function and survival rate and ameliorated morphological damage to heart tissue in LPS-induced mice. Neferine also improved cell viability and mitochondrial function and reduced cell apoptosis and the production of reactive oxygen species in LPS-treated H9c2 cells. In addition, neferine significantly upregulated Bcl-2 expression and suppressed cleaved caspase 3 activity in LPS-induced mouse heart tissue and H9c2 cells. Furthermore, neferine also upregulated the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway in vivo and in vitro. Conversely, LY294002 (a PI3K inhibitor) reversed the protective effect of neferine in LPS-induced H9c2 cells. Our findings thus demonstrate that neferine ameliorates LPS-induced cardiac dysfunction by activating the PI3K/AKT/mTOR signaling pathway and presents a promising therapeutic agent for the treatment of LPS-induced cardiac dysfunction.

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