Puerarin protects rat brain against ischemia/reperfusion injury by suppressing autophagy via the AMPK-mTOR-ULK1 signaling pathway

Wang, Jinfeng; Mei, Zhigang; Fu, Yang; Yang, Songbai; Zhang, Shizhong; Huang, Weifeng; Xiong, Lize; Zhou, Hongbo; Wei, Tao; Feng, Zhaoyong

doi:10.4103/1673-5374.233441

Cited by 91 publications

(30 citation statements)

References 53 publications

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“…In an in vitro model of anoxia/reoxygenation injury in primary cardiomyocytes, puerarin attenuates injury by promoting autophagy and decreasing apoptosis (Ma et al, 2016). However, Wang et al (2018) showed that puerarin protects against ischemia/reperfusion injury in the brain by inhibiting autophagy through the activation of AMPK-mTOR-ULK1 signaling, which is not consistent with the present results. Therefore, the regulatory effect of puerarin on autophagy could be tissue or cell-specific.…”

Section: Discussioncontrasting

confidence: 95%

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Zhu

Zheng

et al. 2020

Front. Physiol.

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Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines to treat patients with diabetic nephropathy (DN). In the previous studies, we showed that puerarin exerts renoprotective effects in Streptozocin (STZ)induced diabetic mice through activation of Sirt1 and anti-oxidative effects. Here, we further investigated the underlying mechanism mediating the renal protective effects of puerarin in DN. We studied the effects and mechanism of puerarin in STZ-induced diabetic mice and in cultured immortalized mouse podocytes treated with high glucose. We confirmed that puerarin ameliorated urinary albumin creatinine ratio and kidney injury in STZ-induced DN mice. We found that expression of heme oxygenase 1 (HMOX-1) and Sirt1 was suppressed in diabetic glomeruli but restored by puerarin treatment at both mRNA and protein levels. Additionally, we found that puerarin induced autophagy in the kidney of DN mice. In conditionally immortalized mouse podocytes, puerarin inhibited HG-induced apoptosis and restored the mRNA and protein levels of HMOX-1 and Sirt1. Interestingly, we showed that puerarin decreased liver kinase B1 (LKB1) acetylation, thereby promoting adenosine 5-monophosphate-activated protein kinase-dependent autophagy. Knockdown of HMOX-1 and Sirt1 expression or treatment with the autophagy inhibitor 3-methyladenine abolished the protective effects of puerarin in HG-treated podocytes. Taken together, these results suggest that puerarin protects podocytes from diabetes-induced injury through HMOX1 and Sirt1-mediated upregulation of autophagy, a novel mechanism explaining its renal protective effects in DN.

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Section: Discussioncontrasting

confidence: 95%

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Zhu

Zheng

et al. 2020

Front. Physiol.

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“…Autophagy is a cellular degradation and recycling process that is highly conserved in all eukaryotes. Animal experimental studies have demonstrated that autophagy plays a double-edged sword role in the central nervous system following CIR injury, especially in neurons [ 13 , 59 – 61 ]. During the first few hours of reperfusion, autophagy played a protective role in CIR injury through degrading damaged organelles and misfolded proteins with the lysosomal system [ 61 – 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…Delays in achieving reperfusion, incomplete recanalization, hemorrhagic transformation, and secondary injury following reperfusion are some of the limitations of intravenous thrombolysis [ 7 ]. Blood reperfusion can result in a series of pathological reactions, including oxidative stress [ 8 ], inflammation [ 9 ], endoplasmic reticulum stress [ 10 ], apoptosis [ 11 , 12 ], and autophagy [ 13 ], leading to cerebral ischemia/reperfusion (CIR) injury, which has been defined as a biochemical cascade causing further worsening of ischemic brain tissue that concomitantly reverses the benefits of restoring circulation following stroke occurrence [ 14 ]. Therefore, it is essential to explore an alternative or complementary medicine including numerous types of pretreatment measurements to prevent or limit CIR injury.…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway

Mei

Huang

Feng

et al. 2020

Aging

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Cerebral ischemia/reperfusion (CIR) injury occurs when blood flow is restored in the brain, causing secondary damage to the ischemic tissues. Previous studies have shown that electroacupuncture (EA) treatment contributes to brain protection against CIR injury through modulating autophagy. Studies indicated that SIRT1-FOXO1 plays a crucial role in regulating autophagy. Here we investigated the mechanisms underlying the neuroprotective effect of EA and its role in modulating autophagy via the SIRT1-FOXO1 signaling pathway in rats with CIR injury. EA pretreatment at “ Baihui ”, “ Quchi ” and “ Zusanli ” acupoints (2/15Hz, 1mA, 30 min/day) was performed for 5 days before the rats were subjected to middle cerebral artery occlusion, and the results indicated that EA pretreatment substantially reduced the Longa score and infarct volume, increased the dendritic spine density and lessened autophagosomes in the peri-ischemic cortex of rats. Additionally, EA pretreatment also reduced the ratio of LC3-II/LC3-I, the levels of Ac-FOXO1 and Atg7, and the interaction of Ac-FOXO1 and Atg7, but increased the levels of p62, SIRT1, and FOXO1. The above effects were abrogated by the SIRT1 inhibitor EX527. Thus, we presume that EA pretreatment elicits a neuroprotective effect against CIR injury, potentially by suppressing autophagy via activating the SIRT1-FOXO1 signaling pathway.

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“…Autophagy is a biological process specific for eukaryotic cell and essential to maintain normal function of cells. A larger number of experiments have demonstrated that autophagy is involved in the pathogenesis of cerebral I/R injury (Luo et al 2017 ; Wang et al 2018 ). Interestingly, ATF-4 as a downstream effector of PERK, can induce the expression of autophagy-related genes, which links ER stress with autophagy (B'Chir et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Acupuncture protects against cerebral ischemia–reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

Sun

Líu

Sun

et al. 2020

Mol Med

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Background Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia–reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), and Qubin (GB7) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

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Puerarin protects rat brain against ischemia/reperfusion injury by suppressing autophagy via the AMPK-mTOR-ULK1 signaling pathway

Cited by 91 publications

References 53 publications

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway

Acupuncture protects against cerebral ischemia–reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

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