Exploring the Multitarget Activity of Wedelolactone against Alzheimer’s Disease: Insights from <i>In Silico</i> Study

Dự, Đặng Xuân; Khang, Nguyen Huu Duy; Tri, Nguyen Huu; Nam, Pham Cam; Thong, Nguyen Minh

doi:10.1021/acsomega.2c08014

Cited by 3 publications

(1 citation statement)

References 75 publications

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“…Both studies have demonstrated that such 4-hydroxycoumarins could be a leading class of novel multitarget-directed ligands for the potential treatment of AD. Du et al [ 154 ] have also attempted to elucidate the anti-AD potential of wedelolactone ( 109 ) by computational studies. Their results indicated that wedelolactone has exceptionally good affinity to both AChE and BChE, could scavenge hydroperoxyl radicals and act as a potent Cu(II) chelator.…”

Section: Coumarin Derivatives As Metal Chelatorsmentioning

confidence: 99%

Targeting Biometals in Alzheimer’s Disease with Metal Chelating Agents Including Coumarin Derivatives

Gucký,

Hamuľaková

2024

CNS Drugs

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Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer’s disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.

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Section: Coumarin Derivatives As Metal Chelatorsmentioning

confidence: 99%

Targeting Biometals in Alzheimer’s Disease with Metal Chelating Agents Including Coumarin Derivatives

Gucký,

Hamuľaková

2024

CNS Drugs

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Melatonin-Related Genes as Key Players in Alzheimer's Disease: Discovery of Promising Biomarkers for Treatment Targets for Alzheimer's Disease

Zhang,

Hamit,

et al. 2024

Preprint

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Background Melatonin can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer’s disease (AD) patients. Hence, our research focused on the potential value of melatonin-related genes (MRGs) in AD through bioinformatic analysis. Methods First, the key cells in the single-cell dataset GSE138852 were screened out based on the proportion of annotated cells and Fisher’s test between the AD and control groups. The differentially expressed genes (DEGs) in the key cell and GSE5281 datasets were identified, and the MRGs in GSE5281 were selected via weighted gene coexpression network analysis. After intersecting two sets of DEGs and MRGs, we performed Mendelian randomization analysis to identify the MRGs causally related to AD. The biomarkers GSE5281 and GSE48350 were identified through receiver operating characteristic (ROC) curve and expression analyses. Furthermore, gene set enrichment analysis, immune infiltration analysis and correlation analysis with metabolic pathways were conducted, as well as construction of a regulator network and molecular docking. Results According to the Fisher test, oligodendrocytes were regarded as key cells due to their excellent abundance in the GSE138852 dataset, in which there were 281 DEGs between the AD and control groups. After overlapping with 3,490 DEGs and 550 MRGs in GSE5281, four genes were found to be causally related to AD, namely,GPRC5B,METTL7A,NFKBIAandRASSF4. Moreover,GPRC5B,NFKBIAandRASSF4were deemed biomarkers, except forMETTL7A, because of their indistinctive expression between the AD and control groups. Biomarkers might be involved in oxidative phosphorylation, adipogenesis and heme metabolism. Moreover, T helper type 17 cells, natural killer cells and CD56dim natural killer cells were significantly correlated with biomarkers. Transcription factors (GATA2, POU2F2, NFKB1, etc.) can regulate the expression of biomarkers. Finally, we discovered that all biomarkers could bind to melatonin with a strong binding energy. Conclusion Our study identified three novel biomarkers related to melatonin for AD, namely,GPRC5B,NFKBIAandRASSF4, providing a novel approach for the investigation and treatment of AD patients.

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Wedelolactone from Eclipta prostrata (L) L. suppresses inflammation and improves insulin resistance

Cuong,

Thien,

Yen

et al. 2024

Asian Pacific Journal of Tropical Biomedicine

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Objective: To evaluate the effects of wedelolactone, a major flavonoid from Vietnamese Eclipta prostrata (L) L., on inflammation and insulin resistance. Methods: Wedelolactone was extracted from the leaves of Vietnamese Eclipta prostrata (L.) L. with methanol by Soxhlet. The effects of wedelolactone on lipopolysaccharide (LPS)-induced cytokine production, reactive oxygen species (ROS) generation, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activities in Raw 264.7 cells were measured by enzyme-linked immunosorbent assay (ELISA), specific immunofluorescent dyes and luminometric analysis, respectively. In addition, its effects on glucose uptake and the protein expression of insulin receptor substrate 1 (IRS1) and glucose transporter 4 (GLUT4) were examined in 3T3-L1 cells by immunofluorescent dyes and Western blot. Results: Wedelolactone at 30 μg/mL significantly inhibited LPS-induced production of tumor necrosis factor-α, interleukin (IL)-6, and IL-8 (P<0.01) with no noticeable effects on IL-10 level. It also reduced ROS generation and NADPH oxidase activities in LPS-stimulated Raw 264.7 cells (P<0.01). Furthermore, wedelolactone showed anti-insulin resistance activity, as evidenced by improved glucose uptake and the upregulated expression of IRS1 and GLUT4 in 3T3-L1 cells (P<0.01). Conclusions: Wedelolactone exhibits anti-inflammation and anti-insulin resistance effects, which may be used for the treatment of diabetes and inflammation-associated diseases.

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Exploring the Multitarget Activity of Wedelolactone against Alzheimer’s Disease: Insights from In Silico Study

Cited by 3 publications

References 75 publications

Targeting Biometals in Alzheimer’s Disease with Metal Chelating Agents Including Coumarin Derivatives

Targeting Biometals in Alzheimer’s Disease with Metal Chelating Agents Including Coumarin Derivatives

Melatonin-Related Genes as Key Players in Alzheimer's Disease: Discovery of Promising Biomarkers for Treatment Targets for Alzheimer's Disease

Wedelolactone from Eclipta prostrata (L) L. suppresses inflammation and improves insulin resistance

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