Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

Tang, Chaoliang; Hong, Junmou; Hu, Chengyun; Huang, Chunxia; Gao, Jie; Huang, Jun; Wang, Di; Geng, Qingwei; Dong, Yongfei

doi:10.1155/2021/6660193

Cited by 43 publications

(25 citation statements)

References 43 publications

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“…AMPK, as a cellular energy sensor, can resist cerebral ischemic injury by switching on catabolic ATP-producing pathways and switching off anabolic ATP-consuming pathways (Marinangeli et al, 2016;Jiang et al, 2018). Palmatine exerts its neuroprotective effect via the activation of the AMPK/Nrf2 pathway (Tang et al, 2021). The AMPK pathway is also involved in the effects of tPA on neuronal apoptosis and mitophagy following stroke (Cai et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

Zhao

Lin

et al. 2021

Front. Pharmacol.

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Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mouse model of T2D stroke. Angiogenesis plays an important role in neuronal survival and functional recovery post-stroke. NmFGF1 promoted angiogenesis in the mouse model of T2D stroke. Furthermore, nmFGF1 reversed the reduction of tube formation and migration in human brain microvascular endothelial cells (HBMECs) cultured in high glucose conditions and treated with oxygen glucose deprivation/re-oxygenation (OGD). Amp-activated protein kinase (AMPK) plays a critical role in the regulation of angiogenesis. Interestingly, we found that nmFGF1 increased the protein expression of phosphorylated AMPK (p-AMPK) both in vivo and in vitro. We found that nmFGF1 promoted tube formation and migration and that this effect was further enhanced by an AMPK agonist (A-769662). In contrast, these processes were inhibited by the application of an AMPK inhibitor (compound C) or siRNA targeting AMPK. Furthermore, nmFGF1 ameliorated neuronal loss in diabetic stroke mice via AMPK-mediated angiogenesis. In addition, nmFGF1 ameliorated glucose and lipid metabolic disorders in our mouse model of T2D stroke without causing significant changes in body weight. These results revealed that nmFGF1-regulated glucolipid metabolism and angiogenesis play a key role in the improvement of functional recovery in a mouse model of T2D stroke and that these effects are mediated by the AMPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

Zhao

Lin

et al. 2021

Front. Pharmacol.

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“…The early intervention strategy of IS refers to restoring the blood supply of infarcted and ischemic areas. Nevertheless, reperfusion is likely to further aggravate ischemic brain injury, i.e., cerebral ischemia/reperfusion (I/R) injury [ 3 , 4 ]. According to related studies and reports, CIRI displays a relationship with energy metabolism disorder [ 5 , 6 ], oxidative stress [ 7 , 8 ], Ca 2+ overload, excitatory neurotransmitters, apoptosis, and necrosis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia-Reperfusion by Regulating Glycolysis through PDK2-PDH-Nrf2 Axis

Zhao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Cerebral ischemic stroke (IS) is still a difficult problem to be solved; energy metabolism failure is one of the main factors causing mitochondrion dysfunction and oxidation stress damage within the pathogenesis of cerebral ischemia, which produces considerable reactive oxygen species (ROS) and opens the blood-brain barrier. Dichloroacetic acid (DCA) can inhibit pyruvate dehydrogenase kinase (PDK). Moreover, DCA has been indicated with the capability of increasing mitochondrial pyruvate uptake and promoting oxidation of glucose in the course of glycolysis, thereby improving the activity of pyruvate dehydrogenase (PDH). As a result, pyruvate flow is promoted into the tricarboxylic acid cycle to expedite ATP production. DCA has a protective effect on IS and brain ischemia/reperfusion (I/R) injury, but the specific mechanism remains unclear. This study adopted a transient middle cerebral artery occlusion (MCAO) mouse model for simulating IS and I/R injury in mice. We investigated the mechanism by which DCA regulates glycolysis and protects the oxidative damage induced by I/R injury through the PDK2-PDH-Nrf2 axis. As indicated from the results of this study, DCA may improve glycolysis, reduce oxidative stress and neuronal death, damage the blood-brain barrier, and promote the recovery of oxidative metabolism through inhibiting PDK2 and activating PDH. Additionally, DCA noticeably elevated the neurological score and reduced the infarct volume, brain water content, and necrotic neurons. Moreover, as suggested from the results, DCA elevated the content of Nrf2 as well as HO-1, i.e., the downstream antioxidant proteins pertaining to Nrf2, while decreasing the damage of BBB and the degradation of tight junction proteins. To simulate the condition of hypoxia and ischemia in vitro, HBMEC cells received exposure to transient oxygen and glucose deprivation (OGD). The DCA treatment is capable of reducing the oxidative stress and blood-brain barrier of HBMEC cells after in vitro hypoxia and reperfusion (H/R). Furthermore, this study evidenced that HBMEC cells could exhibit higher susceptibility to H/R-induced oxidative stress after ML385 application, the specific inhibitor of Nrf2. Besides, the protection mediated by DCA disappeared after ML385 application. To sum up, as revealed from the mentioned results, DCA could exert the neuroprotective effect on oxidative stress and blood-brain barrier after brain I/R injury via PDK2-PDH-Nrf2 pathway activation. Accordingly, the PDK2-PDH-Nrf2 pathway may play a key role and provide a new pharmacology target in cerebral IS and I/R protection by DCA.

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“…It is reported that palmatine activated the Nfr2 knockdown and AMPK pathway [ 168 ]. It is reported for having anti-inflammatory, antioxidative and antiproliferative effects [ 169 ]. Another study reported the combined impact of palmatine and berberine on the inhibition of AChE [ 169 , 170 ].…”

Section: Role Of Antioxidants In Alzheimer’s Diseasementioning

confidence: 99%

“…It is reported for having anti-inflammatory, antioxidative and antiproliferative effects [ 169 ]. Another study reported the combined impact of palmatine and berberine on the inhibition of AChE [ 169 , 170 ]. Though it is reported in several in-silico and in-vivo studies, there is still a massive absence of its proper application in AD.…”

Section: Role Of Antioxidants In Alzheimer’s Diseasementioning

confidence: 99%

Antioxidants in Alzheimer’s Disease: Current Therapeutic Significance and Future Prospects

Pritam

Deka

Bhardwaj

et al. 2022

Biology

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Alzheimer’s disease (AD) rate is accelerating with the increasing aging of the world’s population. The World Health Organization (WHO) stated AD as a global health priority. According to the WHO report, around 82 million people in 2030 and 152 million in 2050 will develop dementia (AD contributes 60% to 70% of cases), considering the current scenario. AD is the most common neurodegenerative disease, intensifying impairments in cognition, behavior, and memory. Histopathological AD variations include extracellular senile plaques’ formation, tangling of intracellular neurofibrils, and synaptic and neuronal loss in the brain. Multiple evidence directly indicates that oxidative stress participates in an early phase of AD before cytopathology. Moreover, oxidative stress is induced by almost all misfolded protein lumps like α-synuclein, amyloid-β, and others. Oxidative stress plays a crucial role in activating and causing various cell signaling pathways that result in lesion formations of toxic substances, which foster the development of the disease. Antioxidants are widely preferred to combat oxidative stress, and those derived from natural sources, which are often incorporated into dietary habits, can play an important role in delaying the onset as well as reducing the progression of AD. However, this approach has not been extensively explored yet. Moreover, there has been growing evidence that a combination of antioxidants in conjugation with a nutrient-rich diet might be more effective in tackling AD pathogenesis. Thus, considering the above-stated fact, this comprehensive review aims to elaborate the basics of AD and antioxidants, including the vitality of antioxidants in AD. Moreover, this review may help researchers to develop effectively and potentially improved antioxidant therapeutic strategies for this disease as it also deals with the clinical trials in the stated field.

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Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

Cited by 43 publications

References 43 publications

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway

DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia-Reperfusion by Regulating Glycolysis through PDK2-PDH-Nrf2 Axis

Antioxidants in Alzheimer’s Disease: Current Therapeutic Significance and Future Prospects

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