Shenzhiling Oral Liquid Protects STZ‐Injured Oligodendrocyte through PI3K/Akt‐mTOR Pathway

Liu, Zhenhong; Qin, Gaofeng; Mana, Lulu; Huang, Songming; Wang, Yahan; Wang, Pengwen

doi:10.1155/2020/4527283

Cited by 7 publications

(4 citation statements)

References 39 publications

(36 reference statements)

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“…As a vital cell signal transduction pathway, the PI3K/AKT signaling pathway has attracted great attention in neurodegenerative diseases due to its inhibition of apoptosis, promotion of cell proliferation, and maintenance of cell cycle regulation. It was reported that the response of the PI3K/Akt signaling pathway was significantly weakened in the hippocampus of AD patients [ 43 ]. AD's pathogenesis involves A β interactions with the PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Mechanism of Shen Huang Chong Ji for Treating Alzheimer’s Disease Based on Network Pharmacology and Experimental Validation

Tang

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The traditional Chinese medicine (TCM) formula, Sheng Huang Chong Ji (SHCJ) is largely applied for treating Alzheimer’s disease (AD), but not much is known regarding its active compounds, molecular targets, and mechanism of action. The current study aimed to predict the potential molecular mechanism of SHCJ against AD based on network pharmacology combined with in vitro validation. Using public databases, SHCJ’s active compounds, their potential targets, and AD-related genes were screened, while Cytoscape Version 3.7.2 was used to build protein–protein interaction (PPI) and compound-disease-target (C-D-T) networks. Analysis of enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms was then carried out in R 4.0.2, including associated packages. Subsequently, molecular docking analysis was performed with AutoDock Vina 1.1.2, with intro experiments involving SH-SY5Y cells used to further investigate the mechanism of SHCJ against AD. Finally, a total of 56 active compounds of SHCJ and 192 SHCJ-AD-related targets were identified. Quercetin was identified as the top potential candidate agent. HSP90AA1, AKT1, and MAPK1 represent potential therapeutic targets. The PI3K-Akt signaling pathway potentially represents a core one mediating the effects of SHCJ against AD. Additionally, molecular docking analysis indicated that quercetin could combine well with AKT1 and multiple apoptosis-related target genes. During cell experiments, a significant increase in cell viability along with a decrease in Aβ25-35-induced apoptosis was observed after treatment with SHCJ. Furthermore, SHCJ significantly increased the phosphorylation of PI3K and Akt while reversing Aβ25-35-induced apoptosis-related protein expression downregulation.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Mechanism of Shen Huang Chong Ji for Treating Alzheimer’s Disease Based on Network Pharmacology and Experimental Validation

Tang

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…In pre-symptomatic and middle-aged APPSwe/PS1ΔE9 (APP/PS1) mice, generation of reactive oxygen species was found to lead to oxidative modification of Akt1 in the synapse resulting in reduction of Akt1-mTOR signaling and deficiency in activity-dependent protein translation; moreover, a similar attenuation of synaptoneurosomal protein translation was found in postmortem AD brains ( Ahmad et al, 2017 ). In cell cultures, STZ-injured oligodendrocytes showed significantly lower expression of PI3K, Akt, p-Akt, mTOR, and p-mTOR proteins than the control group ( Liu et al, 2020 ).…”

Section: Wnt/mtor Pathways Evidence In Alzheimer’s Disease and Attent...mentioning

confidence: 98%

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

et al. 2023

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder with the majority of patients classified as sporadic AD (sAD), in which etiopathogenesis remains unresolved. Though sAD is argued to be a polygenic disorder, apolipoprotein E (APOE) ε4, was found three decades ago to pose the strongest genetic risk for sAD. Currently, the only clinically approved disease-modifying drugs for AD are aducanumab (Aduhelm) and lecanemab (Leqembi). All other AD treatment options are purely symptomatic with modest benefits. Similarly, attention-deficit hyperactivity disorder (ADHD), is one of the most common neurodevelopmental mental disorders in children and adolescents, acknowledged to persist in adulthood in over 60% of the patients. Moreover, for ADHD whose etiopathogenesis is not completely understood, a large proportion of patients respond well to treatment (first-line psychostimulants, e.g., methylphenidate/MPH), however, no disease-modifying therapy exists. Interestingly, cognitive impairments, executive, and memory deficits seem to be common in ADHD, but also in early stages of mild cognitive impairment (MCI), and dementia, including sAD. Therefore, one of many hypotheses is that ADHD and sAD might have similar origins or that they intercalate with one another, as shown recently that ADHD may be considered a risk factor for sAD. Intriguingly, several overlaps have been shown between the two disorders, e.g., inflammatory activation, oxidative stress, glucose and insulin pathways, wingless-INT/mammalian target of rapamycin (Wnt/mTOR) signaling, and altered lipid metabolism. Indeed, Wnt/mTOR activities were found to be modified by MPH in several ADHD studies. Wnt/mTOR was also found to play a role in sAD and in animal models of the disorder. Moreover, MPH treatment in the MCI phase was shown to be successful for apathy including some improvement in cognition, according to a recent meta-analysis. In several AD animal models, ADHD-like behavioral phenotypes have been observed indicating a possible interconnection between ADHD and AD. In this concept paper, we will discuss the various evidence in human and animal models supporting the hypothesis in which ADHD might increase the risk for sAD, with common involvement of the Wnt/mTOR-pathway leading to lifespan alteration at the neuronal levels.

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“…The third aspect is to search for marketed drugs with therapeutic effects on myelin sheath injury, such as clobetasol ( Su et al, 2020 ), trifluoperazine ( Khaledi et al, 2021 ), sildenafil ( Nunes et al, 2016 ), adrenomedullin ( Maki et al, 2015 ), omega-3 polyunsaturated fatty acids ( Pu et al, 2013 ), ascorbic acid ( Nam et al, 2019 ), fluoxetine ( Li et al, 2020a ), melatonin ( Abo Taleb and Alghamdi, 2020 ) and a mixture containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin ( Hauser et al, 2020 ). The fourth facet is to investigate Chinese herbal medicine and its extract that can treat myelin sheath injury, such as Honokiol ( Tan et al, 2022a ), Astaxanthin ( Lotfi et al, 2021 ), Shenling oral liquid ( Liu et al, 2020b ; Zheng et al, 2021 ), Rosmarinic acid ( Li et al, 2020b ), Naringenin ( Rong et al, 2017 ), Salvianolic acid B (78), Tanshinone IIA (79), Bushen Yisui capsule ( Rabinovich and Kacen, 2012 ; Zhao et al, 2018 ), the herbal medicine Ninjin ‘yoeito ( Seiwa et al, 2007 ) and Quercetin ( Naeimi et al, 2018 ; Tan et al, 2022b ), among other medicines.…”

Section: Deficiencies In the Study Of Myelin Sheath Injury And Treatm...mentioning

confidence: 99%

Myelin sheath injury and repairment after subarachnoid hemorrhage

Chen

Guo

et al. 2023

Front. Pharmacol.

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Subarachnoid hemorrhage (SAH) can lead to damage to the myelin sheath in white matter. Through classification and analysis of relevant research results, the discussion in this paper provides a deeper understanding of the spatiotemporal change characteristics, pathophysiological mechanisms and treatment strategies of myelin sheath injury after SAH. The research progress for this condition was also systematically reviewed and compared related to myelin sheath in other fields. Serious deficiencies were identified in the research on myelin sheath injury and treatment after SAH. It is necessary to focus on the overall situation and actively explore different treatment methods based on the spatiotemporal changes in the characteristics of the myelin sheath, as well as the initiation, intersection and common action point of the pathophysiological mechanism, to finally achieve accurate treatment. We hope that this article can help researchers in this field to further clarify the challenges and opportunities in the current research on myelin sheath injury and treatment after SAH.

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Shenzhiling Oral Liquid Protects STZ‐Injured Oligodendrocyte through PI3K/Akt‐mTOR Pathway

Cited by 7 publications

References 39 publications

Pharmacological Mechanism of Shen Huang Chong Ji for Treating Alzheimer’s Disease Based on Network Pharmacology and Experimental Validation

Pharmacological Mechanism of Shen Huang Chong Ji for Treating Alzheimer’s Disease Based on Network Pharmacology and Experimental Validation

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

Myelin sheath injury and repairment after subarachnoid hemorrhage

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