Puerarin provides a neuroprotection against transient cerebral ischemia by attenuating autophagy at the ischemic penumbra in neurons but not in astrocytes

He, Huang; Guo, Tao; Zhang, Pengyue; Yang, Liqiang; Deng, Yong

doi:10.1016/j.neulet.2017.02.009

Cited by 44 publications

(24 citation statements)

References 28 publications

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“…Interestingly, in an adult model of stroke using middle cerebral artery occlusion, a small dose of Tat-Beclin1 (1.5 mg/kg) given i.p. at 6 and 13 days after injury worsened the neurological deficit and increased infarct volumes [36]. Therefore, it was not clear a priori that administering Tat-Beclin1 in this neonatal model of HI injury would be beneficial.…”

Section: Ofmentioning

confidence: 97%

Moderately Inducing Autophagy Reduces Tertiary Brain Injury After Perinatal Hypoxia-Ischemia

Kim

Jeziorek

Kanal

et al. 2020

Preprint

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Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5) – SB505124 – 3 days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated LC3 (light chain 3), a key protein known to mediate autophagy. However, those studies did not determine whether 1) SB was acting directly on the CNS and 2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist 3 days after HI reduced actively apoptotic cells by ∼90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting 3 days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.

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Section: Ofmentioning

confidence: 97%

Moderately Inducing Autophagy Reduces Tertiary Brain Injury After Perinatal Hypoxia-Ischemia

Kim

Jeziorek

Kanal

et al. 2020

Preprint

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“…In addition, a considerable number of studies suggested that Puerarin could regulate the autophagic activity. Some reports have shown that Puerarin upregulates autophagy [11–13], but some studies showed that it inhibits autophagy [14–16]. He et al [14] suggested that Puerarin had neuroprotective effect against cerebral ischemia, which was related to the decrease of autophagic activity in neurons after its intervention.…”

Section: Introductionmentioning

confidence: 99%

“…Some reports have shown that Puerarin upregulates autophagy [11–13], but some studies showed that it inhibits autophagy [14–16]. He et al [14] suggested that Puerarin had neuroprotective effect against cerebral ischemia, which was related to the decrease of autophagic activity in neurons after its intervention. It was also reported that Puerarin could prevent rat brain from ischemia/reperfusion injury through repressing the autophagic response [15].…”

Section: Introductionmentioning

confidence: 99%

Puerarin inhibits the osteoclastogenesis by inhibiting RANKL-dependent and –independent autophagic responses

Zhang

Wang

Tang

et al. 2019

BMC Complement Altern Med

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Background Puerarin exerts therapeutic effect on osteoporosis due to its inhibitory effect on the formation of osteoclasts. Puerarin is also widely established as an autophagy inhibitor. The study aimed to investigate the significance of autophagy in Puerarin-treated osteoclast formation. Methods Osteoclast precursors (OCPs) derived from bone marrow-derived macrophages (BMMs) were treated with Puerarin along with RANKL or without RANKL, and then the autophagic parameters of OCPs (including autophagic proteins, LC3 transformation, autophagosome or LC3-puncta) were observed through Western Blotting, Transmission Electron Microscopy and Immunofluorescence assays. Next, after using overexpression vectors of autophagic genes (Atg7, Atg5 and BECN1) to alter autophagy activity, OCP proliferation was measured by Ethynyl deoxyuridine (EdU) assays and Cell Counting Kit-8 (CCK-8) kit, and osteoclast differentiation was assessed by Tartrate-resistant acid phosphatase (TRAP) staining. Results The results showed that Puerarin could directly inhibit the autophagy and proliferation of OCPs. Importantly, overexpression of autophagic genes Atg5, Atg7 and BECN1 reversed Puerarin-inhibited OCP autophagy and proliferation. What’s more, RANKL could promote the autography of OCPs, which was recovered by Puerarin treatment. Interestingly, different from single-Puerarin treatment, we found that in the presence of RANKL, only BECN1 overexpression significantly reversed Puerarin-inhibited osteoclast differentiation and OCP autophagy. Conclusion In conclusion, Puerarin could inhibit the OCP autophagy in the presence or absence of RANKL, which blocked the OCP proliferation and osteoclast differentiation respectively. Moreover, BECN1 plays an essential role in Puerarin-inhibited osteoclastogenesis. Our study provides potential clue to further complete the intrinsic mechanism of Puerarin in treating osteoporosis.

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“…It has been proved that both of them have significant therapeutic effect against IS. Pue protects against ischemic brain injury in a rat model of transient focal ischemia [ 10 ] and confers a neuroprotection by attenuating autophagy in neurons but not in astrocytes [ 11 ]. Sal-B has been proved having anti-inflammatory and neuroprotective effects against IS insults in vitro and in vivo, which is associated with the inhibition of TLR4 signaling [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Salvianolic Acid B and Puerarin on Cerebral Ischemia Reperfusion Injury

et al. 2018

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Ischemic stroke (IS) is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. It has been a worldwide critical disease threatening to the health and life of human beings. Despite significant progresses achieved, effective treatment still remains a formidable challenge due to the complexity of the disease. Salvianolic acid B (Sal-B) and Puerarin (Pue) are two active neuroprotectants isolated from traditional Chinese herbs, Salvia miltiorrhiza and Kudzu root respectively, which have been used for the prevention and treatment of IS for thousands of years in China. The activities of two compounds against cerebral ischemia reperfusion injury have been confirmed via various pathways. However, the therapeutic efficacy of any of the two components is still unsatisfied. In the present study, the effect of the combination of Sal-B and Pue on IS was evaluated and validated in vitro and in vivo. The ratio of two compounds was firstly optimized based on the results of CoCl2 damaged PC12 cells model. The co-administration exhibited significantly protective effect in CoCl2 induced PC12 cells injury model by reducing ROS, inhibiting apoptosis and improving mitochondrial membrane potential in vitro. Moreover, Sal-B + Pue significantly relieved neurological deficit scores and infarct area than Sal-B or Pue alone in vivo. The results indicated that neuroprotection mechanism of Sal-B + Pue was related to TLR4/MyD88 and SIRT1 activation signaling pathway to achieve synergistic effect, due to the inhibition of NF-κB transcriptional activity and expression of pro-inflammatory cytokine (TNF-α, IL-1β, IL-6). In conclusion, the combination of Sal-B and Pue exerted much stronger neuroprotective effect than Sal-B or Pue alone, which provides a potential new drug and has great significance for the treatment of IS.

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Puerarin provides a neuroprotection against transient cerebral ischemia by attenuating autophagy at the ischemic penumbra in neurons but not in astrocytes

Cited by 44 publications

References 28 publications

Moderately Inducing Autophagy Reduces Tertiary Brain Injury After Perinatal Hypoxia-Ischemia

Moderately Inducing Autophagy Reduces Tertiary Brain Injury After Perinatal Hypoxia-Ischemia

Puerarin inhibits the osteoclastogenesis by inhibiting RANKL-dependent and –independent autophagic responses

Synergistic Effects of Salvianolic Acid B and Puerarin on Cerebral Ischemia Reperfusion Injury

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