Lithium co-administration with rutin improves post-stroke neurological outcomes via suppressing Gsk-3β activity in a rat model

Rana, Anil; Kumar, Rajneesh; Shukla, Durgesh Nandan; Singh, Damanpreet

doi:10.1016/j.freeradbiomed.2023.07.004

Cited by 9 publications

(3 citation statements)

References 61 publications

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“…It seems that following perinatal asphyxia, amyloid protein precursor metabolism is dysregulated and may contribute to the development of Alzheimer's disease in the future by increasing overall amyloid production and reducing the amyloid peptide 1-40/1-42 ratio [23][24][25]. Amyloid can induce tau protein hyperphosphorylation through the activation after asphyxia tau protein kinase GSK-3β [26][27][28]. In addition, GSK-3β has been shown to catalyze the phosphorylation of tau protein through elevated α-synuclein as a result of ischemia, which is important for secondary brain damage after ischemia [27].…”

Section: Discussionmentioning

confidence: 99%

Preservation of Biomarkers Associated with Alzheimer’s Disease (Amyloid Peptides 1-38, 1-40, 1-42, Tau Protein, Beclin 1) in the Blood of Neonates after Perinatal Asphyxia

Tarkowska,

Furmaga-Jabłońska,

Bogucki

et al. 2023

IJMS

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Perinatal asphyxia is a complex disease involving massive death of brain cells in full-term newborns. The most impressive consequence of perinatal asphyxia is a neurodegenerative brain injury called hypoxic–ischemic encephalopathy. Management of newborns after perinatal asphyxia is very difficult due to the lack of measurable biomarkers that would be able to assess the severity of the brain injury in the future, help in the selection of therapy, assess the results of treatment and determine the prognosis for the future. Thus, these limitations make long-term neurodevelopmental outcomes unpredictable during life. Quantifying biomarkers that can detect subclinical changes at a stage where routine brain monitoring or imaging is still mute would be a major advance in the care of neonates with brain neurodegeneration after asphyxia. Understanding the effect of perinatal asphyxia on changes in blood neurodegenerative biomarkers over time, which would be commonly used to assess the severity of postpartum encephalopathy, would be an important step in developing precision in predicting the consequences of brain injuries. We urgently need more accurate early predictive markers to guide clinicians when to use neuroprotective therapy. The needed neurodegenerative biomarkers may represent neuronal pathological changes that can be recognized by new technologies such as genomic and proteomic. Nevertheless, the simultaneous blood tau protein and various amyloid changes with the addition of an autophagy marker beclin 1 after perinatal asphyxia have not been studied. We decided to evaluate serum biomarkers of neuronal injury characteristic for Alzheimer’s disease such as amyloid peptides (1-38, 1-40 and 1-42), tau protein and beclin 1, which can predict the progression of brain neurodegeneration in future. In this paper, we report for the first time the significant changes in the above molecules in the blood after asphyxia compared to healthy controls during the 1–7, 8–14 and 15+ days ELISA test.

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Section: Discussionmentioning

confidence: 99%

Preservation of Biomarkers Associated with Alzheimer’s Disease (Amyloid Peptides 1-38, 1-40, 1-42, Tau Protein, Beclin 1) in the Blood of Neonates after Perinatal Asphyxia

Tarkowska,

Furmaga-Jabłońska,

Bogucki

et al. 2023

IJMS

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“…Lithium activates the MAPK/ERK pathway, which inhibits MMP-9, leading to enhanced BBB stability and reduced leukocyte infiltration in the ischemic brain 197 . Co-administration of lithium and rutin reduces the expression of pro-inflammatory factors in a cerebral ischemia-reperfusion model 198 . Additionally, lithium inhibits the activation of NLRP3 inflammasome, mitigating cerebral ischemic injury 12 .…”

Section: Inflammatory Markersmentioning

confidence: 98%

Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review

Wang,

Lu,

Shi

et al. 2024

Int. J. Med. Sci.

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Ischemic stroke ranks among the foremost clinical causes of mortality and disability, instigating neuronal degeneration, fatalities, and various sequelae. While standard treatments, such as intravenous thrombolysis and endovascular thrombectomy, prove effective, they come with limitations. Hence, there is a compelling need to develop neuroprotective agents capable of improving the functional outcomes of the nervous system. Numerous preclinical studies have demonstrated that lithium can act in multiple molecular pathways, including glycogen synthase kinase 3(GSK-3), the Wnt signaling pathway, the mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling pathway, brain-derived neurotrophic factor (BDNF), mammalian target of rapamycin (mTOR), and glutamate receptors. Through these pathways, lithium has been shown to affect inflammation, autophagy, apoptosis, ferroptosis, excitotoxicity, and other pathological processes, thereby improving central nervous system (CNS) damage caused by ischemic stroke. Despite these promising preclinical findings, the number of clinical trials exploring lithium's efficacy remains limited. Additional trials are imperative to thoroughly ascertain the effectiveness and safety of lithium in clinical settings. This review delineates the mechanisms underpinning lithium's neuroprotective capabilities in the context of ischemic stroke. It elucidates the intricate interplay between these mechanisms and sheds light on the involvement of mitochondrial dysfunction and inflammatory markers in the pathophysiology of ischemic stroke. Furthermore, the review offers directions for future research, thereby advancing the understanding of the potential therapeutic utility of lithium and establishing a theoretical foundation for its clinical application.

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“…Buckwheat is one of the most important sources of rutin . Due to the chemical structure with polyphenolic hydroxyl, rutin has a variety of physiological activities such as antioxidant, − anti-inflammatory, , antivirus, anticancer, , neuroprotective, − cardioprotective, and antidiabetic. , …”

Section: Introductionmentioning

confidence: 99%

Rutin Cocrystals with Improved Solubility, Bioavailability, and Bioactivities

Zhang,

Tang,

Tian

et al. 2024

Crystal Growth & Design

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Rutin is a natural compound that is widely distributed in various plants. Increasing lines of evidence have proved that rutin has a beneficial effect on cardiovascular health, oxidative stress, and blood glucose control. However, the application of rutin is limited due to its poor solubility and low oral bioavailability. To improve the bioavailability of rutin, two cocrystals of rutin with L-proline and D-proline were prepared successfully, and multiple characterization methods were utilized to study the physicochemical properties of rutin and its cocrystals. The powder dissolution in vitro and the pharmacokinetic behavior in vivo were also evaluated. The results indicated that Rut-L-Pro exhibited a significantly improved solubility, and the oral bioavailability also had great improvement; the AUC 0−10h of Rut-L-Pro was 5.6-fold that of rutin, and C max was 3.8 times. As a result of the improvement of rutin bioavailability, Rut-L-Pro performed better blood glucose control and cardioprotective activities.

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Lithium co-administration with rutin improves post-stroke neurological outcomes via suppressing Gsk-3β activity in a rat model

Cited by 9 publications

References 61 publications

Preservation of Biomarkers Associated with Alzheimer’s Disease (Amyloid Peptides 1-38, 1-40, 1-42, Tau Protein, Beclin 1) in the Blood of Neonates after Perinatal Asphyxia

Preservation of Biomarkers Associated with Alzheimer’s Disease (Amyloid Peptides 1-38, 1-40, 1-42, Tau Protein, Beclin 1) in the Blood of Neonates after Perinatal Asphyxia

Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review

Rutin Cocrystals with Improved Solubility, Bioavailability, and Bioactivities

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