Leonurine ameliorates cognitive dysfunction via antagonizing excitotoxic glutamate insults and inhibiting autophagy

Liu, Chunhua; Yin, Hongqiang; Gao, Jing; Xu, Xinfang; Zhang, Tao; Yang, Zhuo

doi:10.1016/j.phymed.2016.10.005

Cited by 20 publications

(10 citation statements)

References 30 publications

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“…In China, Herba leonuri is widely used to treat dysmenorrheal, menoxenia, and gynecological disorders. Studies have indicated that leonurine can ameliorate cognitive dysfunction by inhibiting autophagy [ 8 ], improving the antioxidant capacity of myocardium, promoting angiogenesis in ischemic myocardium, and ameliorating endothelial dysfunction caused by hyperlipidemia [ 9 , 10 ]. Pretreatment with leonurine inhibits ischemic stroke [ 11 ] through antioxidant effects [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of leonurine against oxygen–glucose deprivation by targeting Cx36/CaMKII in PC12 cells

Zhang

Liu

et al. 2018

PLoS ONE

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Leonurine has been reported to play an important role in ameliorating cognitive dysfunction, inhibiting ischemic stroke, and attenuating perihematomal edema and neuroinflammation in intracerebral hemorrhage. However, the exact mechanism and potential molecular targets of this effect remain unclear. Thus, in this study we investigated the neuroprotective effects of leonurine on hypoxia ischemia injury and explored the underlying mechanisms. An in vitro model of oxygen–glucose deprivation (OGD)-induced PC12 cells was established to mimic ischemic-like conditions. Cell viability, apoptosis, Cx36 and pCaMKII/CaMKII expression levels were evaluated after treatment with leonurine. The Cx36-selective antagonist mefloquine and CaMKII Inhibitor KN-93 were used to investigate the neuroprotective effect of leonurine on and the involvement of Cx36/CaMKII in this process. The results revealed that cell viability decreased and cell apoptosis and the protein expression of Cx36 and pCaMKII/CaMKII increased in the OGD-induced PC12 cells. Leonurine significantly increased cell viability and decreased cell apoptosis and the protein expression of Cx36 and pCaMKII/CaMKII in the OGD-induced PC12 cells. The specific inhibitor of Cx36 and CaMKII displayed similar protective effects. Moreover, the inhibition of Cx36 reduced pCaMKII levels and the ratio of pCaMKII/CaMKII in the OGD-induced PC12 cells, and vice versa. Taken together, these results suggest that leonurine might have a protective effect on OGD-induced PC12 cells through targeting the Cx36/CaMKII pathway. Thus, leonurine appears to have potential as a preventive or therapeutic drug against ischemic-induced neuronal injury.

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Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of leonurine against oxygen–glucose deprivation by targeting Cx36/CaMKII in PC12 cells

Zhang

Liu

et al. 2018

PLoS ONE

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“…Ferrucci et al (2018) critically indicated that there was not a unique beneficial role of autophagy in the hypoxic brain and that may be better to inhibit autophagy to alleviate chronic ischemia. For this reason, nutraceuticals like Leonurine, an active extract from Leonorus cardiaca, inhibited ATG pathways and autophagy, so reducing neuronal damage (Liu et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Natural Compounds and Autophagy: Allies Against Neurodegeneration

Stacchiotti

Corsetti

2020

Front. Cell Dev. Biol.

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Prolonging the healthy life span and limiting neurological illness are imperative goals in gerontology. Age-related neurodegeneration is progressive and leads to severe diseases affecting motility, memory, cognitive function, and social life. To date, no effective treatments are available for neurodegeneration and irreversible neuronal loss. Bioactive phytochemicals could represent a natural alternative to ensure active aging and slow onset of neurodegenerative diseases in elderly patients. Autophagy or macroautophagy is an evolutionarily conserved clearing process that is needed to remove aggregateprone proteins and organelles in neurons and glia. It also is crucial in synaptic plasticity. Aberrant autophagy has a key role in aging and neurodegeneration. Recent evidence indicates that polyphenols like resveratrol and curcumin, flavonoids, like quercetin, polyamine, like spermidine and sugars, like trehalose, limit brain damage in vitro and in vivo. Their common mechanism of action leads to restoration of efficient autophagy by dismantling misfolded proteins and dysfunctional mitochondria. This review focuses on the role of dietary phytochemicals as modulators of autophagy to fight Alzheimer's and Parkinson's diseases, fronto-temporal dementia, amyotrophic lateral sclerosis, and psychiatric disorders. Currently, most studies have involved in vitro or preclinical animal models, and the therapeutic use of phytochemicals in patients remains limited.

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“…However, the specific mechanisms of the GABA effect remain unclear. Recently, it has been reported that leonurine exerts neuroprotection by reducing the damage caused by excitatory toxicity [26] . The increased expression levels of GABA and GAD67 in cerebral ischemia after Leo-H pretreatment suggested that increased GABA expression is one of the mechanisms underlying the neuroprotection of leonurine.…”

Section: Discussionmentioning

confidence: 99%

Leonurine protects ischemia-induced brain injury via modulating SOD, MDA and GABA levels

Zheng

Zhu

et al. 2019

Front. Agr. Sci. Eng.

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The present study was designed to investigate the protective effects of leonurine, a compound purified from Herba Leonuri that is active on ischemic rat behavior and cortical neurons, and explore the underlying mechanism. The general rat activity, cortical neuron morphology, superoxide dismutase (SOD), malondialdehyde (MDA), gaminobutyric acid (GABA) and glutamate decarboxylase 67 (GAD67) levels were measured. We found leonurine significantly improve the general activity of rats in an open-field test, which was associated with attenuated neuronal damage induced by ischemia. Moreover, serum SOD activity was significantly greater, MDA level lower in the leonurine group as compared with ischemia group. In addition, GABA content in the cerebral cortex was significantly greater in high-dose leonurine group. Correspondingly, GAD67 protein level coincided with the GABA level. Taken together, our results demonstrated that leonurine attenuated brain injury during ischemia via antioxidative and anti-excitotoxicity effects by targeting GABA and leonurine might become a useful adjuvant neuroprotective agent.

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Leonurine ameliorates cognitive dysfunction via antagonizing excitotoxic glutamate insults and inhibiting autophagy

Cited by 20 publications

References 30 publications

Neuroprotective effects of leonurine against oxygen–glucose deprivation by targeting Cx36/CaMKII in PC12 cells

Neuroprotective effects of leonurine against oxygen–glucose deprivation by targeting Cx36/CaMKII in PC12 cells

Natural Compounds and Autophagy: Allies Against Neurodegeneration

Leonurine protects ischemia-induced brain injury via modulating SOD, MDA and GABA levels

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