Tangeretin Inhibits BACE1 Activity and Attenuates Cognitive Impairments in AD Model Mice

Bao, Jing; Zheng, Liang; Gong, Xiaokang; Zhao, Youcai; Wu, Mengjuan; Liu, Wei; Tu, Chenyu; Wang, Xiaochuan; Shu, Xin

doi:10.1021/acs.jafc.1c07241

Cited by 11 publications

(6 citation statements)

References 50 publications

(93 reference statements)

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“…[ 42 ] Thus, once the loaded nanoparticle is internalized, IRW could prevent NFκB translocation into the nuclei, both in cancer and endothelial cells. [ 17,43 ]…”

Section: Resultsmentioning

confidence: 99%

Dermatan Sulfate/Chitosan Nanoparticles Loaded with an Anti‐Inflammatory Peptide Increase the Response of Human Colorectal Cancer Cells to 5‐Fluorouracil

Blachman,

Birocco,

Curcio

et al. 2023

Macromolecular Bioscience

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The gold standard drug for colorectal cancer (CRC) treatment, 5‐Fluorouracil (5‐FU), induces pharmacological tolerance in long‐term management. The transcriptional factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NFκB) plays a key role in 5‐FU resistance. The aim of this work is to study the capability of polyelectrolytes complex nanoparticles of dermatan sulfate (DS) and chitosan (CS), loaded with the anti‐inflammatory tripeptide IRW, to sensitize colorectal cancer cells to 5‐FU. Fluorescence and flow cytometry studies confirmed the recognition by the nanoformulation, of the cluster of differentiation 44 (CD44) receptor, involved in the initiation and progression of colorectal tumors. Dynamic light scattering (DLS) and flow cytometry reinforced the importance of DS and CD44 receptor in the interaction, as the addition of DS or anti‐CD44 antibody blocked the binding. Moreover, the nanoformulation also interacts with 3D colon cancer cultures, namely colonospheres, enriched in cancer stem cells (CSC), subpopulation responsible for drug resistance and metastasis. To evaluate the consequences of this interaction, the subcellular distribution of the transcriptional factor NFκB, is determined by immunofluorescence analysis. Internalization and the intracellular release of IRW inhibited nuclear translocation of NFκB and increased cellular sensitivity to 5‐FU. Altogether, the nanoformulation could provide a selective delivery platform for IRW distribution to colorectal tumors, being an innovative strategy toward overcoming 5‐FU resistance in CRC therapy.

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“…[ 42 ] Thus, once the loaded nanoparticle is internalized, IRW could prevent NFκB translocation into the nuclei, both in cancer and endothelial cells. [ 17,43 ]…”

Section: Resultsmentioning

confidence: 99%

Dermatan Sulfate/Chitosan Nanoparticles Loaded with an Anti‐Inflammatory Peptide Increase the Response of Human Colorectal Cancer Cells to 5‐Fluorouracil

Blachman,

Birocco,

Curcio

et al. 2023

Macromolecular Bioscience

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“…The authors found that TAN treatment (100 mg/kg body weight/day) significantly ameliorated the cognitive dysfunction and reduced amyloid beta (Aβ) aggregation and synaptic loss in an APPswe/PSEN1dE9 transgenic (Tg) mice AD model. A mechanistic study revealed that TAN could inhibit β-secretase in both in vitro and in vivo studies, proving TAN's potential role in the management of AD pathogenesis [22].…”

Section: Effect Of Tan In Ad Modelsmentioning

confidence: 99%

“…Although research on the beneficial effects of TAN in relation to AD and AD pathology are limited, some of the published data indicate that it can play a positive role in the management of AD pathology. In recent study by Shu et al at the Institutes of Biomedical Sciences, School of Medicine, Jianghan University, China, the effects of TAN in an AD model of mice were evaluated [22]. The authors found that TAN treatment (100 mg/kg body weight/day) significantly ameliorated the cognitive dysfunction and reduced amyloid beta (Aβ) aggregation and synaptic loss in an APPswe/PSEN1dE9 transgenic (Tg) mice AD model.…”

Section: Effect Of Tan In Ad Modelsmentioning

confidence: 99%

“…Ethnopharmacological studies on TAN have revealed numerous biological and functional properties, including antioxidant, anti-carcinogenic, anti-inflammatory, anti-atherogenic, and hepatoprotective properties, as well as actions on the neurological and proliferative fronts [19,20]. Pre-clinical studies have also indicated that TAN possesses neuroprotective and cognitive-enhancing benefits in cellular and in vivo experimental models including AD and PD [21][22][23][24]. Mechanistic-based studies indicated that TAN is involved in the regulation of multiple oxidative and inflammatory-related signaling pathways such as the inhibition of ROS, pro-inflammatory mediators, the regulation of NF-κB, MAPKs and JNK, and AKT activation [25].…”

Section: Introductionmentioning

confidence: 99%

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An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders

Wani,

Koppula,

Balda

et al. 2024

Life

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Neuroinflammation is the major cause of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Currently available drugs present relatively low efficacy and are not capable of modifying the course of the disease or delaying its progression. Identifying well-tolerated and brain-penetrant agents of plant origin could fulfil the pressing need for novel treatment techniques for neuroinflammation. Attention has been drawn to a large family of flavonoids in citrus fruits, which may function as strong nutraceuticals in slowing down the development and progression of neuroinflammation. This review is aimed at elucidating and summarizing the effects of the flavonoid tangeretin (TAN) in the management of neuroinflammation-mediated neurodegenerative disorders. A literature survey was performed using various resources, including ScienceDirect, PubMed, Google Scholar, Springer, and Web of Science. The data revealed that TAN exhibited immense neuroprotective effects in addition to its anti-oxidant, anti-diabetic, and peroxisome proliferator-activated receptor-γ agonistic effects. The effects of TAN are mainly mediated through the inhibition of oxidative and inflammatory pathways via regulating multiple signaling pathways, including c-Jun N-terminal kinase, phosphoinositide 3-kinase, mitogen-activated protein kinase, nuclear factor erythroid-2-related factor 2, extracellular-signal-regulated kinase, and CRE-dependent transcription. In conclusion, the citrus flavonoid TAN has the potential to prevent neuronal death mediated by neuroinflammatory pathways and can be developed as an auxiliary therapeutic agent in the management of neurodegenerative disorders.

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“…To date, dozens of PMFs have been isolated and identified from citrus plants, and their types and contents are different with the type of citrus species [ 1 ]. Tangeretin (5,6,7,8,4′-pentamethoxyflavone, TAN), one of the most abundant PMFs in citrus peel, has been reported to possess several biological activities, including anti-oxidative, anti-inflammatory, hepatoprotective, neuroprotective, anti-obesity, and anticancer effects [ 2 , 3 , 4 , 5 , 6 , 7 ]. Certain studies in previous years have shown that 5-hydroxylated PMFs formed during storage by the autohydrolysis of PMFs in citrus fruits exhibited more potent bioactivities than their PMF counterparts [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Acetylation Enhances the Anticancer Activity and Oral Bioavailability of 5-Demethyltangeretin

Tsai

Yang

Chen

et al. 2022

IJMS

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A kind of hydroxylated polymethoxyflavone (PMFs) existing in the citrus genus, 5-Demethyltangeretin (5-DTAN), has been reported to possess several bioactivities in vitro and in vivo. The aim of this study was to investigate whether acetylation could enhance the anticancer activity and oral bioavailability of 5-DTAN. PC-3 human prostate cancer cells were treated with tangeretin (TAN), 5-DTAN, and 5-acetylated TAN (5-ATAN), and the results showed that the cytotoxic effect 5-ATAN (IC50 value of 5.1 µM) on the cell viability of PC-3 cells was stronger than that of TAN (IC50 value of 17.2 µM) and 5-DTAN (IC50 value of 11.8 µM). Compared to 5-DTAN, 5-ATAN treatment caused a more pronounced DNA ladder, increased the sub-G1 phase population, and induced G2/M phase arrest in the cell cycle of PC-3 cells. We also found that 5-ATAN triggered the activation of caspase-3 and the progression of the intrinsic mitochondrial pathway in PC-3 cells, suggesting the induction of apoptosis. In a cell wound healing test, 5-ATAN dose-dependently reduced the cell migration, and the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was decreased after 48 h of 5-ATAN treatment. Moreover, oral administration of 5-ATAN showed a significantly stronger inhibitory effect on tumor size and tumor weight in tumor-bearing nude mice than those of vehicle or the 5-DTAN group (p < 0.05). Furthermore, pharmacokinetic results showed that single-dose oral administration of 5-ATAN exhibited a higher maximum concentration (Cmax) and area under the curve (AUC) of 5-DTAN in plasma than that of 5-DTAN. More extensive distribution of 5-DTAN to most tissues of mice was also observed in mice treated with 5-ATAN for 7 days. In conclusion, acetylation strongly enhances the anticancer activity and oral bioavailability of 5-DTAN and could be a promising strategy to promote the potential bioactivities of natural products.

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Tangeretin Inhibits BACE1 Activity and Attenuates Cognitive Impairments in AD Model Mice

Cited by 11 publications

References 50 publications

Dermatan Sulfate/Chitosan Nanoparticles Loaded with an Anti‐Inflammatory Peptide Increase the Response of Human Colorectal Cancer Cells to 5‐Fluorouracil

Dermatan Sulfate/Chitosan Nanoparticles Loaded with an Anti‐Inflammatory Peptide Increase the Response of Human Colorectal Cancer Cells to 5‐Fluorouracil

An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders

Acetylation Enhances the Anticancer Activity and Oral Bioavailability of 5-Demethyltangeretin

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