Maslinic acid promotes synaptogenesis and axon growth via Akt/GSK-3β activation in cerebral ischemia model

Qian, Yisong; Huang, Minda; Guan, Teng; Chen, Lan; Cao, Liangxun; Han, Xiao‐Jian; Huang, Longfei; Tang, Xuzhen; Li, Yunman; Sun, Hongbin

doi:10.1016/j.ejphar.2015.07.028

Cited by 35 publications

(14 citation statements)

References 41 publications

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“…44 Maslinic acid facilitated axonal regeneration by regulating the Akt/GSK3β signaling pathway to provide neuroprotection in an animal model of middle cerebral artery occlusion. 45 What is more, the PI3K–GSK3β signaling pathway was involved in sensory axon regeneration, as shown by the increased level of GSK3β phosphorylation that was validated by an acute depletion of Smad1. 46 Since many microtubule-associated proteins (MAPs) including MAP1B are regarded as GSK3β substrates, GSK3β is an important regulator of neuronal microtubules.…”

Section: Discussionmentioning

confidence: 99%

Taurine attenuates acrylamide-induced axonal and myelinated damage through the Akt/GSK3β-dependent pathway

Sun

Wang

et al. 2018

Int J Immunopathol Pharmacol

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Acrylamide (ACR), formed during the Maillard reaction induced by high temperature in food processing, is one of the main causes of neurodegenerative diseases. Taurine, a free intracellular β-amino acid, is characterized by many functions, including antioxidation, anti-inflammatory, and neuroprotective properties. This promotes its application in the treatment of neurodegenerative diseases. In this study, the neuroprotective effects of taurine against ACR-induced neurotoxicity and the potential underlying mechanisms were explored. Rats were intoxicated with ACR and injected with taurine in different groups for totally 2 weeks between January and July 2017. Electron microscopic analysis was used to observe the changes in tissues of the rats. Meanwhile, the levels of proteins including p-Akt, p-GSK3β, SIM312, and MBP were detected by Western blot. Furthermore, the GSK3β phosphorylation in taurine-treated dorsal root ganglion (DRG) with ACR was examined in the presence of the Akt inhibitor, MK-2206. The analysis of behavioral performances and electron micrographs indicated that taurine treatment significantly attenuated the toxic manifestations induced by ACR and stimulated the growth of axons and the medullary sheath, which was associated with the activation of the Akt/GSK3β signaling pathway. Mechanistically, it was found that taurine activated GSK3β, leading to significant recovery of the damage in ACR-induced sciatic nerves. Furthermore, MK-2206, an inhibitor of Akt, was applied in DRG cells, suggesting that taurine-induced GSK3β phosphorylation was Akt dependent. Our findings demonstrated that taurine attenuated ACR-induced neuropathy in vivo, in an Akt/GSK3β-dependent manner. This confirmed the treatment with taurine to be a novel strategy against ACR-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Taurine attenuates acrylamide-induced axonal and myelinated damage through the Akt/GSK3β-dependent pathway

Sun

Wang

et al. 2018

Int J Immunopathol Pharmacol

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“…The outgrowth length in combotherapy group was 172.78 ± 14.47 µm/cell, and it was significantly higher than the group with NaB or Nico solo treatment (84.72 ± 16.29 µm/cell and 116.75 ± 26.27 µm/cell, respectively) ( Figure 5E). It has been reported that increasing PI3k activity could improve neurite outgrowth of the neurons in stroke rodent model 41 and by considering more activity of PI3k after combo small molecule treatment, we could see this increase in our transplanted neurons.…”

Section: Increasing the Length Of Neurite Outgrowth By Treating Witmentioning

confidence: 54%

Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy

Hosseini

Ziaee

Haider³

et al. 2018

J of Cellular Biochemistry

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Poor survival of stem cells in the harsh microenvironment at the site of stroke, especially during acute phase of injury, remains a serious obstacle to achieve the desired prognosis. We hypothesized that combined treatment of neural stem cells (NSCs) with small molecules would precondition them to become robust and survive better as compared with the native nonpreconditioned cells. Mouse ganglionic NSCs were isolated, cultured, and characterized. The cells were preconditioned by treatment with sodium butyrate (NaB) and nicorandil (Nico) and transplanted in an experimentally induced stroke model. Sham-operated animals without treatment or animals with experimental stroke treated with basal medium, native NSCs, NSCs preconditioned with NaB or Nico alone were used as controls. The tissue samples and cells with different treatments were used to measure brain-tissue-derived neurotrophic factor (BDNF) level and the activity of phosphatidylinositol-3 kinase (PI3K), apurinic/apyrimidinic endonuclease 1 (APE1), and nuclear factor-κB (NF-κB) p50 both in vitro and in vivo, respectively. Additionally, survival of the cells and recovery indices for stroke were studied. The combined treatment with NaB + Nico resulted in increased BDNF level and higher PI3K, APE1, and the downstream NF-κB activation, which were blocked by pretreatment with their respective inhibitors. Donor cell survival increased postengraftment as assessed by 5-bromo-2'-deoxyuridine immunostaining and reduced Terminal deoxynucleotide transferase dUTP Nick End Labeling positivity at the site of engraftment. There was reduction in proinflammatory cytokines and infiltration of both GFAP and CD68 at the injury site. There was reduction in the infarct size and neurological function was preserved in the preconditioned cell treatment group. Our preconditioning approach with small molecules effectively improved the survival as well as functionality of NSCs.

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“…For example, maslinic acid from the Olea europaea plant promotes synaptogenesis and axonal regeneration by regulating the Akt/GSK-3β signaling pathway. 89 Asiatic acid from Centella asiatica decreases glutamate-induced cognitive deficits, blood-brain barrier permeability, and mitochondrial injury during cerebral ischemia. 90 , 91 Our results suggest that betulin is a new pentacyclic triterpene with antiparkinsonian properties.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Betulin in Pharmacological and Transgenic Caenorhabditis elegans Models of Parkinson’s Disease

Tsai

Liu

et al. 2017

Cell Transplant

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Parkinson’s disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Current therapeutics for PD provides satisfactory symptom relief but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process. Betulin is derived from the bark of birch trees and possesses anticancer, antimicrobial, and anti-inflammatory properties. The aim of the present study was to evaluate the potential for betulin to ameliorate PD features in Caenorhabditis elegans (C. elegans) models. We demonstrated that betulin diminished α-syn accumulation in the transgenic C. elegans model. Betulin also reduced 6-hydroxydopamine-induced dopaminergic neuron degeneration, reduced food-sensing behavioral abnormalities, and reversed life-span decreases in a pharmacological C. elegans model. Moreover, we found that the enhancement of proteasomes activity by promoting rpn1 expression and downregulation of the apoptosis pathway gene, egl-1, may be the molecular mechanism for betulin-mediated protection against PD pathology. Together, these findings support betulin as a possible treatment for PD and encourage further investigations of betulin as an antineurodegenerative agent.

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Maslinic acid promotes synaptogenesis and axon growth via Akt/GSK-3β activation in cerebral ischemia model

Cited by 35 publications

References 41 publications

Taurine attenuates acrylamide-induced axonal and myelinated damage through the Akt/GSK3β-dependent pathway

Taurine attenuates acrylamide-induced axonal and myelinated damage through the Akt/GSK3β-dependent pathway

Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy

Neuroprotective Effects of Betulin in Pharmacological and Transgenic Caenorhabditis elegans Models of Parkinson’s Disease

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