Harpagide inhibits neuronal apoptosis and promotes axonal regeneration after spinal cord injury in rats by activating the Wnt/β-catenin signaling pathway

Rong, Yuluo; Liu, Wei; Zhou, Zheng; Gong, Fangyi; Bai, Jianling; Fan, Jin; Li, Linwei; Luo, Yi; Zhou, Zhimin; Cai, Wei

doi:10.1016/j.brainresbull.2019.03.014

Cited by 28 publications

(32 citation statements)

References 19 publications

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“…Secondary injury has a significant effect on SCI and is caused by various factors including apoptosis, oxidative stress, inflammation and autophagy. 1,15 This present work is the first demonstration that BMSC-Exos can suppress neuronal apoptosis enhancing autophagy and improving the behavioral function of rats. Briefly, the abundance of autophagy-related protein LC3IIB and Beclin-1 were found to be increased by BMSC-Exos, which also promoted the autophagosomes formation.…”

Section: Discussionmentioning

confidence: 66%

<p>Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Improves Spinal Cord Function After Injury in Rats by Activating Autophagy</p>

J¹,

Jin²,

Wang³

et al. 2020

DDDT

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Background: Spinal cord injury (SCI) is a global medical problem. The smallest membrane-bound nanovesicles, known as exosomes, have a role in complex intercellular communication systems and can be used directly as therapeutic agents by acting as important paracrine factors. Nevertheless, the use of exosomes derived from BMSCs (BMSC-Exos) to treat SCI has been less, and the specific mechanism has not yet been reported. Methods: BMSC-Exos were characterized by TEM, NTA and Western blot. The effects of BMSC-Exos treatment were compared by SCI in vivo model and a series of in vitro experiments. Results: BMSC-Exos were found to enhance the expression of autophagy-related proteins LC3IIB and Beclin-1 and enabled autophagosomes formation. After BMSC-Exos treatment, there was marked decline in the level of expression of proapoptotic protein cleaved caspase-3, while that of the antiapoptotic protein Bcl-2 was upregulated. Conclusion: BMSC-Exos can attenuate neuronal apoptosis by promoting autophagy and promote the potential efficacy of functional behavior recovery in SCI rats. In summary, these findings expand the theoretical knowledge and forms a realistic route for the future treatment of SCI by BMSC-Exos.

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Section: Discussionmentioning

confidence: 66%

<p>Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Improves Spinal Cord Function After Injury in Rats by Activating Autophagy</p>

J¹,

Jin²,

Wang³

et al. 2020

DDDT

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“…Multiple studies have revealed that activation of the Wnt/β-catenin signaling pathway could inhibit neuronal apoptosis [ 35 , 36 ]. Recent studies indicated that Pb exposure caused spatial memory deficits and apoptosis in the brain via the Wnt/β-catenin pathway [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

et al. 2020

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Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/β-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

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“…During the development of the nervous system, the Wnt protein family plays an important role in regulating axon regeneration and in the pathogenesis of neuropathic pain. Wnt5a plays an important role in central sensitization and neuronal plasticity in acute and chronic pain [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Wang

et al. 2020

Neural Plasticity

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At present, most of the drugs have little effect on the pathological process of rheumatoid arthritis (RA). Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease. Some studies have found that crocin, a kind of Chinese medicine, can effectively alleviate pain sensitization in pain model rats, but the mechanism is not clear. Emerging evidence indicates that crocin may inhibit the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/β-catenin and the Wnt signaling pathway is closely related to RA. Wnt5a belongs to the Wnt protein family and was previously thought to be involved only in nonclassical Wnt signaling pathways. Recent studies have shown that Wnt5a has both stimulatory and inhibitory effects on the classical Wnt signaling pathway, and so, Wnt5a has attracted increasing attention. This study demonstrated that crocin significantly increased the mechanical thresholds of adjuvant-induced arthritis (AIA) rats, suggesting that crocin can alleviate neuropathic pain. Crocin significantly decreased the levels of pain-related factors and glial activation. Foxy5, activator of Wnt5a, inhibited the above effects of crocin in AIA rats. In addition, intrathecal injection of a Wnt5a inhibitor significantly decreased hyperalgesia in AIA rats. This research shows that crocin may alleviate neuropathic pain in AIA rats by inhibiting the expression of pain-related molecules through the Wnt5a/β-catenin pathway, elucidating the mechanism by which crocin relieves neuropathic pain and provides a new way of thinking for the treatment of AIA pain.

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Harpagide inhibits neuronal apoptosis and promotes axonal regeneration after spinal cord injury in rats by activating the Wnt/β-catenin signaling pathway

Cited by 28 publications

References 19 publications

<p>Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Improves Spinal Cord Function After Injury in Rats by Activating Autophagy</p>

<p>Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Improves Spinal Cord Function After Injury in Rats by Activating Autophagy</p>

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

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