DPP‐4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high‐glucose conditions, potentially through the SIRT1/HIF‐1/VEGF pathway

Mi, Donghua; Fang, Hongjuan; Zheng, Guanghui; Liang, Xiaohu; Ding, Yu; Liu, Xin; Liu, Liping

doi:10.1111/cns.13042

Cited by 26 publications

(25 citation statements)

References 49 publications

(103 reference statements)

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“…However, additional cellular mechanisms may be involved. Indeed, Mi et al (65) showed that linagliptin increases the in vitro proliferation of rat brain microvascular endothelial cells via the SIRT1/HIF-1α/VEGF pathway. Furthermore, recent works have shown that linagliptin improves cerebrovascular dysfunction and remodeling in a rat model of T2D, independent of glycemic control (66, 67).…”

Section: Linagliptin Provides Acute Neuroprotection After Stroke In Ementioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibitors for the Potential Treatment of Brain Disorders; A Mini-Review With Special Focus on Linagliptin and Stroke

et al. 2019

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Cerebral stroke is a leading cause of death and persistent disability of elderly in the world. Although stroke prevention by targeting several risk factors such as diabetes and hypertension has decreased the stroke incidence, the total number of strokes is increasing due to the population aging and new preventive therapies are needed. Moreover, post-stroke acute pharmacological strategies aimed to reduce stroke-induced brain injury have failed in clinical trials despite being effective in animal models. Finally, approximately 30% of surviving stroke patients do not recover from stroke and remain permanently dependent on supportive care in activities of daily living. Therefore, strategies to improve stroke recovery in the post-acute phase are highly needed. Linagliptin is a dipeptidyl peptidase-4 inhibitor which is clinically approved to reduce hyperglycemia in type 2 diabetes. The regulation of glycemia by dipeptidyl peptidase-4 inhibition is mainly achieved by preventing endogenous glucagon-like peptide-1 (GLP-1) degradation. Interestingly, linagliptin has also shown glycaemia-independent beneficial effects in animal models of stroke, Parkinson's disease and Alzheimer's disease. In some case the preclinical data have been supported with some clinical data. Although potentially very interesting for the development of new strategies against stroke and neurodegenerative disorders, the mode of action of linagliptin in the brain is still largely unknown and seems to occur in a GLP-1R-independent manner. The purpose of this mini-review is to summarize and discuss the recent experimental and clinical work regarding the effects of linagliptin in the central nervous system, with special emphasis on acute neuroprotection, stroke prevention and post-stroke recovery. We also highlight the main questions in this research field that need to be addressed in clinical perspective.

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Section: Linagliptin Provides Acute Neuroprotection After Stroke In Ementioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibitors for the Potential Treatment of Brain Disorders; A Mini-Review With Special Focus on Linagliptin and Stroke

et al. 2019

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“…On the basis of our data from Western blotting and RT‐PCR in ICR mice, leonurine upregulated VEGF at the levels of both protein and mRNA. VEGF is widely expressed in the brain tissue, mainly through choroid plexus, neurons, astrocytes, and vascular endothelium . However, investigations on VEGF localization during the acute phase of ischemic stroke are limited.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of leonurine against ischemic stroke in mice by activating nuclear factor erythroid 2‐related factor 2 pathway

Xie

Zhang

et al. 2019

CNS Neurosci Ther

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Aims Leonurine has been shown to trigger antioxidant responses during ischemic stroke, and nuclear factor erythroid 2‐related factor 2 (Nrf‐2) imparts protective effects against oxidative injury. The present study has determined that leonurine prevents ischemic injury of brain tissues via Nrf‐2 pathway activation. Methods Male ICR mice and Nrf‐2−/− mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and received leonurine treatment at 2 hours after pMCAO by intraperitoneal injection. Neurological deficit scores as well as infarct volume were assessed to determine the neuroprotective role of leonurine. Nrf‐2 was investigated using Western blotting and real‐time polymerase chain reaction (RT‐PCR) analysis to elucidate the neuroprotective mechanism of leonurine. Commercial kits were employed to determine reactive oxygen species (ROS), superoxide (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px), malonaldehyde (MDA), and glutathione (GSH). Vascular endothelial growth factor (VEGF) was evaluated by Western blotting and RT‐PCR analysis, and VEGF was localized using immunofluorescence. Results The application of leonurine on ICR mice resulted in an improvement in neurological deficit scores and a reduction in infarct volume. Leonurine upregulated nuclear Nrf‐2 protein and increased total Nrf‐2 protein expression and mRNA levels. Leonurine regulated SOD, MDA, CAT, GSH, and GSH‐Px, and it significantly inhibited ROS production in ICR mice. Leonurine improved VEGF expression and increased VEGF expression in neurons, astrocytes, and endothelial cells. However, leonurine had no obvious beneficial effects on Nrf‐2−/− mice. Conclusions Leonurine exerted neuroprotective effects, promoted antioxidant responses, and upregulated VEGF expression by activating the Nrf‐2 pathway.

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“…Altogether, these findings suggest that the activation of AMPK is necessary for berberine to regulate endothelium-dependent vasodilation. In rat brain, berberine protected microvascular endothelial cells from hypoxia/high-glucose-induced impairment through the SIRT1/HIF-1α/VEGF pathway (Mi et al, 2019).…”

Section: Anti-diabetes Activities Of Rhizoma Coptidismentioning

confidence: 99%

Rhizoma coptidis as a Potential Treatment Agent for Type 2 Diabetes Mellitus and the Underlying Mechanisms: A Review

Ran

Wang

et al. 2019

Front. Pharmacol.

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Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), has become a significant public health burden. Rhizoma coptidis (RC), known as Huang Lian , is widely used for treating diabetes in China. The bioactive compounds of RC, especially alkaloids, have the potential to suppress T2DM-induced lesions, including diabetic vascular dysfunction, diabetic heart disease, diabetic hyperlipidemia, diabetic nephropathy, diabetic encephalopathy, diabetic osteopathy, diabetic enteropathy, and diabetic retinopathy. This review summarizes the effects of RC and its bioactive compounds on T2DM and T2DM complications. Less research has been conducted on non-alkaloid fractions of RC, which may exert synergistic action with alkaloids. Moreover, we summarized the pharmacokinetic properties and structure-activity relationships of RC on T2DM with reference to extant literature and showed clearly that RC has potential therapeutic effect on T2DM.

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DPP‐4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high‐glucose conditions, potentially through the SIRT1/HIF‐1/VEGF pathway

Abstract: The protection of rBMVECs from hypoxia/high-glucose induced impairment by DPP-4 inhibitors may be mediated by the SIRT1/HIF-1α/VEGF pathway.

Cited by 26 publications

References 49 publications

Dipeptidyl Peptidase-4 Inhibitors for the Potential Treatment of Brain Disorders; A Mini-Review With Special Focus on Linagliptin and Stroke

Dipeptidyl Peptidase-4 Inhibitors for the Potential Treatment of Brain Disorders; A Mini-Review With Special Focus on Linagliptin and Stroke

Protective effects of leonurine against ischemic stroke in mice by activating nuclear factor erythroid 2‐related factor 2 pathway

Rhizoma coptidis as a Potential Treatment Agent for Type 2 Diabetes Mellitus and the Underlying Mechanisms: A Review

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