Ginsenoside Rb1 Promotes Motor Functional Recovery and Axonal Regeneration in Post-stroke Mice through cAMP/PKA/CREB Signaling Pathway

Gao, Xuan; Zhang, Xiangjian; Cui, Lili; Chen, Rong; Zhang, Cong; Xue, Jing; Zhang, Lan; He, Weiliang; Li, Jiamin; Wei, Shanshan; Wei, Mengmeng; Cui, Hemei

doi:10.1016/j.brainresbull.2019.10.006

Cited by 49 publications

(29 citation statements)

References 71 publications

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“…Interestingly, patients without apparent improvement still exhibited complex changes over time due to motor network connectivity [ 91 ]. Investigated mechanisms of motor functional recovery include axonal sprouting [ 92 , 93 ], white matter repair [ 94 ], neurogenesis [ 95 ], and ipsilesional/contralesional network reorganization [ 96 ]. Just as consequences of stroke disability maladaptively alter cortical mapping and hinder recovery [ 97 ], interventions targeting beneficial neuroplastic reorganization can strengthen tracts and improve recovery [ 98 , 99 ].…”

Section: Motor Pathway Disruptionmentioning

confidence: 99%

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

et al. 2020

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Stroke research has traditionally focused on the cerebral processes following ischemic brain injury, where oxygen and glucose deprivation incite prolonged activation of excitatory neurotransmitter receptors, intracellular calcium accumulation, inflammation, reactive oxygen species proliferation, and ultimately neuronal death. A recent growing body of evidence, however, points to far-reaching pathophysiological consequences of acute ischemic stroke. Shortly after stroke onset, peripheral immunodepression in conjunction with hyperstimulation of autonomic and neuroendocrine pathways and motor pathway impairment result in dysfunction of the respiratory, urinary, cardiovascular, gastrointestinal, musculoskeletal, and endocrine systems. These end organ abnormalities play a major role in the morbidity and mortality of acute ischemic stroke. Using a pathophysiology-based approach, this current review discusses the pathophysiological mechanisms following ischemic brain insult that result in end organ dysfunction. By characterizing stroke as a systemic disease, future research must consider bidirectional interactions between the brain and peripheral organs to inform treatment paradigms and develop effective, comprehensive therapeutics for acute ischemic stroke.

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Section: Motor Pathway Disruptionmentioning

confidence: 99%

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

et al. 2020

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“…Interestingly, folic acid has been reported to improve endothelial function [ 45 ] and alleviate various microglia-mediated neuroinflammation via the Notch1/nuclear factor kappa B p65 pathway in the hippocampus following brain I/R injury in rats [ 46 ]. Ginsenoside Rb1, an active component extracted from Ginseng Radix et Rhizoma , was found to bind to three GPCR targets and has been reported to promote poststroke axonal regeneration by activating the cAMP/PKA/CREB signaling pathway [ 47 ]. Few studies have investigated the vasorelaxant and anti-ischemic stroke effects of the three compounds of XXMD, namely, gallotannin, liquiritin apioside, and narirutin, which bound to all the five vascular GPCR targets.…”

Section: Discussionmentioning

confidence: 99%

Xiaoxuming Decoction Regulates Vascular Function by Modulating G Protein-Coupled Receptors: A Molecular Docking Study

Shen

Yang

Zhou

et al. 2021

BioMed Research International

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Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (β2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.

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“…Thus, H89 confers protection from brain damage in many aspects of nervous system function. Conversely, several reports have shown that the effects of some neuroprotective agents are eliminated by H89 intervention [30][31][32]. One explanation for these ndings is that these neuroprotective agents protect neurons against ischemia through the cAMP/PKA/CREB signaling pathways, promote the phosphorylation of p-CREB, and play important anti-apoptotic roles.…”

Section: Discussionmentioning

confidence: 99%

Stargazin Interaction With Serine Racemase Mediates Cerebral Ischemia/Reperfusion Injury in Rats

Yuan

Diao

Chen

et al. 2021

Preprint

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D-Serine is thought to be involved in N-methyl-D-aspartate (NMDA)-type glutamate receptor-mediated neurotoxicity and plays a pathophysiologic role in stroke. D-Serine is synthesized by serine racemase (SR), which directly converts L-serine into D-serine. The deletion of SR has been reported to protect against cerebral ischemia damage. Additionally, SR catalytic activity is physiologically regulated by its binding to stargazin. However, whether the stargazin-SR interaction affects the level of stroke damage remains elusive. We showed that cerebral ischemia increased the interaction of stargazin and SR and decreased the levels of D-serine. Disrupting the stargazin-SR interaction by knocking down stargazin aggravated cerebral ischemic insults. We found that cerebral ischemia decreased the phosphorylation of stargazin at the Thr-321 residue, which was phosphorylated by cAMP-dependent protein kinase A (PKA). Treatment with the PKA inhibitor H89 blocked stargazin T321 phosphorylation, augmented the stargazin-SR interaction, decreased D-serine levels, and alleviated focal cerebral ischemic damage in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Thus, the stargazin-SR interaction is a promising strategy in the treatment of stroke.

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Ginsenoside Rb1 Promotes Motor Functional Recovery and Axonal Regeneration in Post-stroke Mice through cAMP/PKA/CREB Signaling Pathway

Cited by 49 publications

References 71 publications

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

Xiaoxuming Decoction Regulates Vascular Function by Modulating G Protein-Coupled Receptors: A Molecular Docking Study

Stargazin Interaction With Serine Racemase Mediates Cerebral Ischemia/Reperfusion Injury in Rats

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