Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus

Zu, Guoxiu; Sun, Keyun; Li, Ling; Zu, Xiuli; Han, Tao; Huang, Hailiang

doi:10.1038/s41598-021-02248-5

Cited by 46 publications

(26 citation statements)

References 45 publications

(43 reference statements)

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“…Quercetin reduces the concentration of blood glucose levels, preserves the function of islets cells, number of β cell numbers in model rats and mice with diabetes. Experiments show that quercetin intake has a positive impact to prevent and treat the occurrence of diabetes mellitus [62,69].…”

Section: Diabetesmentioning

confidence: 99%

Health Benefits of Quercetin in Age-Related Diseases

2022

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Polyphenols are the known group of phytochemicals that essentially consists of phenolic rings. These are the plant product present in varied fruits and vegetables. These secondary metabolites perform a protective function in plants from environmental and biological stress. When consumed as a human diet these are also known to prevent various age-associated diseases. Polyphenols are known to possess antioxidant properties and protect against oxidative stress. The literature survey was carried out using databases such as PubMed, Science direct and Springer. The research articles from last 10–12 years were selected for this review based on its relevancy with the topic. The articles selected was mainly focused on quercetin and its health benefits. The present review highlights the main functions of a flavonoid, quercetin. Quercetin is among the widely occurring polyphenol, found abundantly in nature. It is commonly present in different plant products. Onion is known to have the highest quantity of quercetin. This plant compound is possessed antioxidant properties and is considered to have a protective function against aging. It is known to be present in both free and conjugated forms. Quercetin has anti-oxidative, anti-inflammatory, anti-proliferative, anti-carcinogenic, anti-diabetic, and anti-viral properties. The molecule is lipophilic and can easily cross the BBB (Blood-Brain Barrier) and hence protects from neurodegenerative diseases. Various in vivo and in vitro studies have demonstrated the role of quercetin and here a detailed review of quercetin as a curative agent in neurodegeneration, diabetes, cancer, and inflammation has been carried out. Studies have proved that quercetin plays a crucial role in the prevention of age-related disorders. Quercetin is a potent antioxidant which is currently being used in various pharmaceuticals. Properties of quercetin can be further explored in various other disorders. Nanoformulations and liposomal formulations of quercetin can be made to treat other age associated diseases.

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Section: Diabetesmentioning

confidence: 99%

Health Benefits of Quercetin in Age-Related Diseases

2022

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“…( Deshpande et al, 2008 ; Prasad et al, 2016 ). VEGFA and JUN were identified as the central players in diabetic nephropathy ( Oltean et al, 2015 ; Wang et al, 2021 ) and Alzheimer’s disease ( Zu et al, 2021 ) whereas, VEGFA was associated with diabetic retinopathy ( Bucolo et al, 2021 ), cardiac autonomic neuropathy ( Ravichandran et al, 2019 ), and non-alcoholic fatty liver disease-hepatocellular carcinoma ( Shen et al, 2022 ). Each hub gene plays a vital and diverse role in the pathways and biological processes.…”

Section: Discussionmentioning

confidence: 99%

Coexpression network analysis of human candida infection reveals key modules and hub genes responsible for host-pathogen interactions

Naik

Mohammed

2022

Front. Genet.

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Invasive fungal infections are a significant reason for morbidity and mortality among organ transplant recipients. Therefore, it is critical to investigate the host and candida niches to understand the epidemiology of fungal infections in transplantation. Candida albicans is an opportunistic fungal pathogen that causes fatal invasive mucosal infections, particularly in solid organ transplant patients. Therefore, identifying and characterizing these genes would play a vital role in understanding the complex regulation of host-pathogen interactions. Using 32 RNA-sequencing samples of human cells infected with C. albicans, we developed WGCNA coexpression networks and performed DESeq2 differential gene expression analysis to identify the genes that positively correlate with human candida infection. Using hierarchical clustering, we identified 5 distinct modules. We studied the inter- and intramodular gene network properties in the context of sample status traits and identified the highly enriched genes in the correlated modules. We identified 52 genes that were common in the most significant WGCNA turquoise module and differentially expressed genes in human endothelial cells (HUVEC) infection vs. control samples. As a validation step, we identified the differentially expressed genes from the independent Candida-infected human oral keratinocytes (OKF6) samples and validated 30 of the 52 common genes. We then performed the functional enrichment analysis using KEGG and GO. Finally, we performed protein-protein interaction (PPI) analysis using STRING and CytoHubba from 30 validated genes. We identified 8 hub genes (JUN, ATF3, VEGFA, SLC2A1, HK2, PTGS2, PFKFB3, and KLF6) that were enriched in response to hypoxia, angiogenesis, vasculogenesis, hypoxia-induced signaling, cancer, diabetes, and transplant-related disease pathways. The discovery of genes and functional pathways related to the immune system and gene coexpression and differential gene expression analyses may serve as novel diagnostic markers and potential therapeutic targets.

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“…What's more, quercetin increased the expression of brain-derived BDNF and SIRT1 protein, which indicated a neuroprotective role of quercetin (Hu et al, 2020). A recent study aimed to identify the potential target of quercetin suggested that quercetin may have a synergic effect on DM and AD by targeting MAPK pathways (Zu et al, 2021).…”

Section: Quercetinmentioning

confidence: 99%

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Wang

Liu

et al. 2023

Front. Pharmacol.

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Alzheimer’s Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although the exact etiology of AD is still not fully elucidated, aberrant metabolism including insulin signaling and mitochondria dysfunction plays an important role in the development of AD. Binding to insulin receptor substrates, insulin can transport through the blood-brain barrier (BBB), thus mediating insulin signaling pathways to regulate physiological functions. Impaired insulin signaling pathways, including PI3K/Akt/GSK3β and MAPK pathways, could cause damage to the brain in the pathogenesis of AD. Mitochondrial dysfunction and overexpression of TXNIP could also be causative links between AD and DM. Some antidiabetic medicines may have benefits in the treatment of AD. Metformin can be beneficial for cognition improvement in AD patients, although results from clinical trials were inconsistent. Exendin-4 may affect AD in animal models but there is a lack of clinical trials. Liraglutide and dulaglutide could also benefit AD patients in adequate clinical studies but not semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such as saxagliptin, vildagliptin, linagliptin, and sitagliptin could boost cognitive function in animal models. And SGLT2 inhibitors such as empagliflozin and dapagliflozin were also considerably protective against new-onset dementia in T2DM patients. Insulin therapy is a promising therapy but some studies indicated that it may increase the risk of AD. Herbal medicines are helpful for cognitive function and neuroprotection in the brain. For example, polyphenols, alkaloids, glycosides, and flavonoids have protective benefits in cognition function and glucose metabolism. Focusing on glucose metabolism, we summarized the pharmacological mechanism of hypoglycemic drugs and herbal medicines. New treatment approaches including antidiabetic synthesized drugs and herbal medicines would be provided to patients with AD. More clinical trials are needed to produce definite evidence for the effectiveness of hypoglycemic medications.

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Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus

Cited by 46 publications

References 45 publications

Health Benefits of Quercetin in Age-Related Diseases

Health Benefits of Quercetin in Age-Related Diseases

Coexpression network analysis of human candida infection reveals key modules and hub genes responsible for host-pathogen interactions

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

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