Asiaticoside Alleviates Cerebral Ischemia-Reperfusion Injury via NOD2/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Zhang, Chunhui; Chen, Suyan; Zhang, Zhenxiang; Xu, Hui; Zhang, Wei Hong; Xu, Dongqing; Lin, Beilei; Mei, Yongxia

doi:10.12659/msm.920325

Cited by 28 publications

(26 citation statements)

References 31 publications

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“…A key pathway of inflammation in central nervous system injury is the NF-κB pathway, which regulates the expression of pro-inflammatory and pro-apoptosis genes in its active form ( Howell and Bidwell, 2020 ). Neuroprotective effect may be achieved by regulating MAPK and NF-κB signaling pathways and thus regulating inflammatory responses ( Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The Alteration of M6A-Tagged Transcript Profiles in the Retina of Rats After Traumatic Optic Neuropathy

Zhu

et al. 2021

Front. Genet.

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Messager RNA (mRNA) can be modified in a variety of ways, among which the modification of N6-methyladenosine (m6A) is one of the most common ones. Recent studies have found that the m6A modification in mRNA could functionally regulate the splicing, localization, translation, and stability of mRNA, which might be closely related to multiple diseases. However, the roles of m6A modification in traumatic optic neuropathy (TON) are unknown. Herein, we detected the expression of m6A-related genes via quantitative real-time PCR (qRT-PCR) and performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) as well as RNA-sequencing to analyze the alteration profiles of m6A modification after TON. The results showed that the expression of m6A-related genes (METTL3, WTAP, FTO, and ALKBH5) were all upregulated after TON. In all, 2,810 m6A peaks were differentially upregulated and 689 m6A peaks were downregulated. In addition, the hypermethylated and hypomethylated profiles of mRNA transcripts were also identified. To sum up, our study revealed the differentially expressed m6A modification in the early stage of TON, which may provide novel insights into the mechanism and treatment of TON.

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Section: Discussionmentioning

confidence: 99%

The Alteration of M6A-Tagged Transcript Profiles in the Retina of Rats After Traumatic Optic Neuropathy

Zhu

et al. 2021

Front. Genet.

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“…In particular, the degradation pathways of the monoamine neurotransmitter precursors have been reported to be activated by inflammatory factors, which may lead to an increase in the levels of these neurotransmitters ( 10 ). A previous study also showed that asiaticoside exhibited a strong anti-inflammatory effect in animal models of cognitive deficits, spinal cord injury and cerebral ischemia-reperfusion injury ( 27 , 33 , 34 ). In the present study, it was demonstrated that CMS increased hippocampal IL-1β, IL-6 and TNF-α levels, which were alleviated by asiaticoside administration, thus indicating that the antidepressant effect of asiaticoside may be due to its anti-inflammatory properties.…”

Section: Discussionmentioning

confidence: 87%

“…Furthermore, it was demonstrated that asiaticoside inhibited the activation of pNF-κBp65, NLRP3 and caspase-1, leading to a reduction in the levels of inflammatory cytokines and subsequent inflammatory response. It has also been reported that asiaticoside may attenuate inflammation by downregulating pNF-κBp65 and the levels of inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, in a rat model of β-amyloid-induced Alzheimers disease ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…Asiaticoside has also been shown to exert a strong anti-inflammatory effect in animal models of osteoarthritis, spinal cord injury and peritonitis ( 26 ). Moreover, asiaticoside may exert beneficial effects in central nervous system (CNS) disorders, including Parkinsons disease and dementia ( 27 ). It has been reported that the antidepressant properties of asiaticoside are mediated via activation of the BDNF/tropomyosin receptor kinase B (TrkB) signaling pathway in the chronic unpredictable mild stress (CMS) mouse model ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

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Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway

Wang

Guo

et al. 2020

Mol Med Rep

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asiaticoside is one of the triterpenoid components found in Centella asiatica that has promising neuroprotective properties. The present study aimed to evaluate the antidepressant-like properties of asiaticoside and to investigate the possible mechanisms underlying its mode of action using a mouse model of chronic unpredictable mild stress (cMS). Behavioral tests, including sucrose preference test, forced swimming test and tail suspension test, were performed to evaluate symptoms of depression. The expression levels of neurotransmitters, 5-hydroxytryptamine (5-HT) and norepinephrine (ne), in the hippocampus were measured by high-performance liquid chromatography. eliSa and western blotting were used to detect protein expression. it was demonstrated that asiaticoside treatment (20 and 40 mg/kg; intragastric) significantly reversed the decrease in sucrose consumption, and reduced the immobility time in tail suspension tests and forced swimming tests in cMS mice. Furthermore, asiaticoside treatment upregulated the expression of 5-HT and ne in the cMS mouse model. asiaticoside administration also downregulated the levels of interleukin (il)-1β, il-6 and tumor necrosis factor-α in the hippocampus, and reduced the phosphorylation of nuclear factor (nF)-κBp65 and the expression of nod-like receptor protein 3 (nlrP3), thus decreasing the expression of mature caspase-1. Furthermore, asiaticoside significantly increased the levels of cAMP and protein kinase a (PKa), and enhanced phosphorylation of the cAMP-related specific marker vasodilator-stimulated phosphoprotein at serine 157. Therefore, asiaticoside may activate the caMP/PKa signaling pathway to inhibit nF-κB-and NLRP3-related inflammation. Moreover, phosphorylation of the caMP-responsive element-binding protein at serine 133 and the expression of brain-derived neurotrophic factor were increased after asiaticoside administration. collectively, the present results suggested that asiaticoside may play a vital role as an antidepressant and anti-inflammatory agent in the CMS mouse model by regulating the caMP/PKa signaling pathway.

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“…The prevention and treatment of CIRI have gained increased attention in the field of global IR research ( 24 , 25 ). Blocking neuronal apoptosis is the most important step in alleviating CIRI ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis

Kong

Cheng

et al. 2021

Mol Med Rep

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Orexin-A (OXA) protects neurons against cerebral ischemia-reperfusion injury (CIRI). Endoplasmic reticulum stress (ERS) induces apoptosis after CIRI by activating caspase-12 and the CHOP pathway. The present study aimed to determine whether OXA mitigates CIRI by inhibiting ERS-induced neuronal apoptosis. A model of CIRI was established, in which rats were subjected to middle cerebral artery occlusion with ischemic intervention for 2 h, followed by reperfusion for 24 h. Neurological deficit examination and 2,3,5-triphenyltetrazolium chloride staining were performed to assess the level of CIRI and neuroprotection by OXA. Expression levels of ERS-related proteins and cleaved caspase-3 were measured via western blotting, while the rate of neuronal apoptosis in the cortex was determined using a TUNEL assay. OXA treatment decreased the infarct volume of rats after CIRI and attenuated neuron apoptosis. Furthermore, administration of OXA decreased the expression levels of GRP78, phosphorylated (p)-PERK, p-eukaryotic initiation factor-2α, p-inositol requiring enzyme 1α, p-JNK, cleaved caspase-12, CHOP and cleaved caspase-3, all of which were induced by CIRI. Collectively, these findings suggested that OXA attenuated CIRI by inhibiting ERS-mediated apoptosis, thus clarifying the mechanism underlying its neuroprotective effect and providing a novel therapeutic direction for the treatment of CIRI.

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Asiaticoside Alleviates Cerebral Ischemia-Reperfusion Injury via NOD2/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Cited by 28 publications

References 31 publications

The Alteration of M6A-Tagged Transcript Profiles in the Retina of Rats After Traumatic Optic Neuropathy

The Alteration of M6A-Tagged Transcript Profiles in the Retina of Rats After Traumatic Optic Neuropathy

Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway

Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis

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