Aconiti lateralis Radix Praeparata
 inhibits Alzheimer’s disease by regulating the complex regulation network with the core of
 GRIN1
 and
 MAPK1

Wang, Yutao; Zhang, Huixiang; Wang, Jing; Yu, Ming; Zhang, Qianqian; Yan, Shanchun; You, Dingyun; Shi, Lan-Lan; Zhang, Lihuan; Wang, Limei; Wu, Hong-Xiang; Cao, Xue

doi:10.1080/13880209.2021.1900879

Cited by 6 publications

(3 citation statements)

References 62 publications

(121 reference statements)

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“…The DEGs obtained were remarkably enriched in GO terms and pathway under defense response, whole membrane, molecular transducer activity, neutrophil degranulation, ion transport, integral component of plasma membrane, transporter activity and neuronal system. [76], BTK (Bruton tyrosine kinase) [77], C7 [78], PLA2G7 [79], SOCS3 [80], OLR1 [81], LIPA (lipase A, lysosomal acid type) [82], CD86 [83], TLR5 [ [100], AGRN (agrin) [101] and GP6 [102] have been shown as a promising biomarkers in Alzheimer's disease. Field et al [103], Lincoln et al [104], Ziliotto et al [105], El Sharkawi et al [106], Cossins et al [107], Mirowska-Guzel et al [108], Asouri et al [109], Cardamone et al [110], Begovich et al [111], Bennetts et al [112], Iparraguirre et al [113] and Oldoni et al [114] reported that HLA-DPB1, HLA-DQA1, CCL18, CCL20, MMP7, IL1A, IL2RA, CYBB (cytochrome b-245 beta chain), PTPN22, HLA-DMB, ANXA2 and CHIT1expression were associated with progression of multiple sclerosis, but these genes might be liable for advancement of dementia.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein protein interaction (PPI) network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis and RT PCR. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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“…Fuzi considerably induced growth of cell projection and cell proliferation in 0.4–0.8 mg/mL and 1.6–100 mg/mL, respectively, in the AD cell model. In addition, the involvement of GRIN1 and MAPK1 genes contributed to the antiAD mechanism of action [ 125 ].…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Neuropharmacological Potential of Diterpenoid Alkaloids

et al. 2023

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This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the β-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity.

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“…Among the four botanical drugs, Artemisia capillaris Thunb. [Asteraceae; Artemisiae scopariae herba] and Aconitum carmichaelii Debeaux [Ranunculaceae, Aconiti lateralis radix praeparata] possess antioxidant, anti-inflammatory, and anti-apoptotic effects; Zingiber officinale Roscoe [Zingiberaceae, Zingiberis rhizoma] and honey-fried Glycyrrhiza glabra L. [Fabaceae, Glycyrrhizae radix et rhizoma praeparata cum melle] mainly play harmonic roles in detoxifying Aconitum carmichaelii Debeaux [Ranunculaceae, Aconiti lateralis radix praeparata], and these metabolites of YCSND synergistically exert positive effects in the body ( Wang M. F. et al, 2021 ; Wang Y. et al, 2021 ; Huang et al, 2021 ). Recent pharmacological studies have shown that YCSND has hepatoprotective properties, and some metabolites occurring in YCSND, including scoparone ( Hsueh et al, 2021 ), glycyrrhizic acid ( Huo et al, 2020 ), and chlorogenic acid ( Merzouk et al, 2017 ) have been reported to exert hepatoprotective effects.…”

Section: Introductionmentioning

confidence: 99%

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Zheng,

Shi,

Meng

et al. 2023

Front. Pharmacol.

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Objective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics.Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI.Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI.Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM.

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Aconiti lateralis Radix Praeparata inhibits Alzheimer’s disease by regulating the complex regulation network with the core of GRIN1 and MAPK1

Cited by 6 publications

References 62 publications

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Neuropharmacological Potential of Diterpenoid Alkaloids

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

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