Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes

Ye, Xun-jia; Xu, Rong; Liu, Siying; Hu, Bo; Shi, Zi-Jian; Shi, Fuli; Zeng, Bo; Xu, Lihui; Huang, Yuanting; Chen, Ming-Ye; Zha, Qing-Bing; He, Xian-Hui; Ouyang, Dong-Yun

doi:10.1016/j.intimp.2021.108380

Cited by 11 publications

(4 citation statements)

References 45 publications

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“…Con A was injected into mice to build hepatitis animal model, [ 38 , 39 ] and the experimental procedure was illustrated in Figure 6C . The injected Con A could accumulate in liver to activate the immune system and induce T‐cell‐dependent liver damage.…”

Section: Resultsmentioning

confidence: 99%

A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self‐Polymerization

et al. 2023

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Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the development of effective gene vector. Herein a novel gene delivery strategy by just using natural polyphenol (‐)‐epigallocatechin‐3‐O‐gallate (EGCG) as raw material is reported. EGCG first intercalates into nucleic acids to yield a complex, which then oxidizes and self‐polymerizes to form tea polyphenols nanoparticles (TPNs) for effective nucleic acids encapsulation. This is a general method to load any types of nucleic acids with single or double strands and short or long sequences. Such TPNs‐based vector achieves comparable gene loading capacity to commonly used cationic materials, but showing lower cytotoxicity. TPNs can effectively penetrate inside cells, escape from endo/lysosomes, and release nucleic acids in response to intracellular glutathione to exert biological functions. To demonstrate the in vivo application, an anti‐caspase‐3 small interfering ribonucleic acid is loaded into TPNs to treat concanavalin A‐induced acute hepatitis, and excellent therapeutic efficacy is obtained in combination with the intrinsic activities of TPNs vector. This work provides a simple, versatile, and cost‐effective gene delivery strategy. Given the biocompatibility and intrinsic biofunctions, this TPNs‐based gene vector holds great potential to treat various diseases.

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Section: Resultsmentioning

confidence: 99%

A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self‐Polymerization

et al. 2023

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“…Among the T cells, we can see that CD8 + effector T cells were most obviously different between young and aged liver. To further study the alteration of inflammation level, especially CD8 + T cell infiltration, in the aged liver with injury, we established a classical autoimmune hepatitis model [ 35 , 36 , 37 ] by using 15 mg kg −1 concanavalin A (conA) in young and aged mice, in which CD8 + T cells were reported to play main roles at the stage of hepatocyte apoptosis and liver injury. [ 38 ] Eight hours after conA injection, we quantified total T‐cells by detecting CD3‐positive cells using flow cytometry and immunohistochemistry.…”

Section: Resultsmentioning

confidence: 99%

Hippo Pathway Activation in Aged Mesenchymal Stem Cells Contributes to the Dysregulation of Hepatic Inflammation in Aged Mice

et al. 2023

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Aging is always accompanied by chronic diseases which probably attribute to long‐term chronic inflammation in the aging body. Whereas, the mechanism of chronic inflammation in aging body is still obscure. Mesenchymal stem cells (MSCs) are capable of local chemotaxis to sites of inflammation and play a powerful role in immune regulation. Whether degeneration of MSCs in the aging body is associated with unbalanced inflammation is still not clear. In this study, immunosuppressive properties of aged MSCs are found to be repressed. The impaired immunosuppressive function of aged MSCs is associated with lower expression of the Hippo effector Yes‐associated protein 1 (YAP1) and its target gene signal transducer and activator of transcription 1 (STAT1). YAP1 regulates the transcription of STAT1 through binding with its promoter. In conclusion, a novel YAP1/STAT1 axis maintaining immunosuppressive function of MSCs is revealed and impairment of this signal pathway in aged MSCs probably resulted in higher inflammation in aged mice liver.

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“…Our study extends these findings by demonstrating TAX's impact on BCa cell apoptosis. Interestingly, TAX exhibited anti-tumor efficacy in a mouse model of hepatocellular carcinoma, involving T lymphocytes [18], prompting further exploration of its effects on the BCa microenvironment. Additionally, TAX has shown promise in attenuating melanoma progression by targeting the ROS-mediated PI3K/Akt pathway [19].…”

Section: Discussionmentioning

confidence: 99%

Taraxasterol stimulates apoptosis of BCa cells via restraining PI3K/AKT and epidermal growth factor receptor (EGFR)

2024

EJGO

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Breast cancer (BCa) is a prevalent form of tumor, necessitating the development of more effective therapeutic drugs to improve patient prognosis. Taraxasterol (TAX), derived from the dandelion plant, has demonstrated significant physiological and pharmacological activity, but its role in BCa and underlying mechanism remains unexplored. In this study, we investigate the effects of TAX on the growth, motility and apoptosis of BCa cells in vitro to determine its mechanistic actions. Our results demonstrate that TAX significantly reduces both the proliferation and motility of BCa cells and induces apoptosis in BCa cells, as confirmed through flow cytometry (FCM). This apoptotic effect was further supported by JC-1 staining, which showed alterations in mitochondrial membrane potential in BCa cells after TAX treatment. Mechanistically, TAX suppresses the phosphatidylinositide 3-kinases/protein kinase B (PI3K/AKT) and EGFR pathways and impedes BCa progression. Collectively, TAX stimulates BCa cell apoptosis by inhibiting the PI3K/AKT and EGFR pathways.

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Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes

Cited by 11 publications

References 45 publications

A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self‐Polymerization

A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self‐Polymerization

Hippo Pathway Activation in Aged Mesenchymal Stem Cells Contributes to the Dysregulation of Hepatic Inflammation in Aged Mice

Taraxasterol stimulates apoptosis of BCa cells via restraining PI3K/AKT and epidermal growth factor receptor (EGFR)

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