Qingda Granule Attenuates Angiotensin II-Induced Renal Apoptosis and Activation of the p53 Pathway

Long, Linzi; Zhang, Xiuli; Wen, Ying; Li, Jiapeng; Wei, Lihui; Cheng, Ying; Liu, Huixin; Chu, Jianfeng; Fang, Yi; Xie, Qiurong; Shen, Aling; Peng, Jun

doi:10.3389/fphar.2021.770863

Cited by 13 publications

(6 citation statements)

References 40 publications

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“…Given the role of choline and AD in cardiac dysfunction (Millard et al, 2018 ; Yang, Li, et al, 2020 ; Yang, Jiang, et al, 2020 ), we examined cardiac pathology. We first assessed heart weight normalized by tibia length as a measure of pathological cardiac hypertrophy (Long et al, 2022 ); NonTg ChN ( n = 9), NonTg Ch‐ ( n = 7), 3xTg‐AD ChN ( n = 4), and 3xTg‐AD Ch‐ ( n = 6). We found significant main effects of genotype ( F (1, 22) = 29.63, p < 0.0001) and diet ( F (1, 22) = 13.78, p = 0.001), where 3xTg‐AD mice had a higher heart weight than NonTg mice (Figure 3a ).…”

Section: Resultsmentioning

confidence: 99%

Dietary choline intake is necessary to prevent systems‐wide organ pathology and reduce Alzheimer's disease hallmarks

et al. 2023

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There is an urgent need to identify modifiable environmental risk factors that reduce the incidence of Alzheimer's disease (AD). The B‐like vitamin choline plays key roles in body‐ and brain‐related functions. Choline produced endogenously by the phosphatidylethanolamine N‐methyltransferase protein in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ~90% of Americans do not reach the recommended daily intake of dietary choline. Thus, it's imperative to determine whether dietary choline deficiency increases disease outcomes. Here, we placed 3xTg‐AD, a model of AD, and non‐transgenic (NonTg) control mice on either a standard laboratory diet with sufficient choline (ChN; 2.0 g/kg choline bitartrate) or a choline‐deficient diet (Ch‐; 0.0 g/kg choline bitartrate) from 3 to 12 (early to late adulthood) months of age. A Ch‐ diet reduced blood plasma choline levels, increased weight, and impaired both motor function and glucose metabolism in NonTg mice, with 3xTg‐AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, elevated soluble and insoluble Amyloid‐β and Thioflavin S structures, and tau hyperphosphorylation at various pathological epitopes in the hippocampus and cortex of 3xTg‐AD Ch‐ mice. To gain mechanistic insight, we performed unbiased proteomics of hippocampal and blood plasma samples. Dietary choline deficiency altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, dietary choline deficiency altered protein networks associated with insulin metabolism, mitochondrial function, inflammation, and fructose metabolic processing. Our data highlight that dietary choline intake is necessary to prevent systems‐wide organ pathology and reduce hallmark AD pathologies.

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Section: Resultsmentioning

confidence: 99%

Dietary choline intake is necessary to prevent systems‐wide organ pathology and reduce Alzheimer's disease hallmarks

et al. 2023

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“…Given the role of choline in cardiac dysfunction and previous reports of cardiac dysfunction in AD (5, 16), we examined cardiac pathology. We first measured heart weight normalized by tibia length as a measure of pathological cardiac hypertrophy (20); NonTg ChN (n = 9), NonTg Ch- (n = 7), 3xTg-AD ChN (n = 4), and 3xTg-AD Ch- (n = 6). We found significant main effects of genotype (F (1,22) = 29.63, p < 0.0001) and diet (F (1,22) = 13.78, p = 0.001), where 3xTg-AD mice had a higher heart weight than NonTg mice.…”

Section: Resultsmentioning

confidence: 99%

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer’s disease hallmarks

Dave

Judd

Decker

et al. 2022

Preprint

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Evidence suggests that environmental factors may contribute to Alzheimers disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ~90% of Americans do not reach the recommended daily choline intake. Thus, it is imperative to determine whether dietary deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a sufficient choline (ChN) or choline deficient (Ch-; choline deficiency) diet from 3 to 12 (early to late adulthood) months of age. Ch- reduced plasma choline and acetylcholine levels, increased weight, and impaired both glucose metabolism and motor function in NonTg, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, and elevated Amyloid-beta and phosphorylated tau in the hippocampus and cortex of 3xTg-AD Ch- mice. Unbiased proteomic analyses revealed Ch- altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, Ch- altered protein networks associated with insulin metabolism, mitochondrial function, and inflammation. Collectively, our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce AD hallmark pathologies.

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“…Our current study identi ed the overlapping gene analysis was performed and 31 common genes were found between quercetin and hypertensive renal injury targets. In addition, STRING database and Cytoscape software were used for analysis and obtained potential gene targets, including EGFR, XDH, TP53, BaX, THF, IL6, and Bcl-2 with different binding potential with quercetin, among them, TP53, BaX, TNF, IL6 and Bcl-2 have been reported to be involved in hypertension [55][56][57] . GO and KEGG analysis showed that the therapeutic effects of quercetin on hypertensive renal injury involves multiple signaling pathways (including apoptosis and p53 signaling pathway), therefore, we investigated whether quercetin treatment employs its functional role on hypertensive renal injury via this pathway.…”

Section: Discussionmentioning

confidence: 99%

An integrated network pharmacology and RNA-seq approach for exploring the renal protection of quercetin on attenuating Ang II- induced cells apoptosis

Zhang

et al. 2023

Preprint

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Quercetin exerts antihypertensive effects, while its role on hypertensive renal injury remain unknown. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and BaX) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Hematoxylin and eosin staining revealed that quercetin treatment reduced the pathological changes in renal tissues of Ang II infused mice. RNA sequencing identified quercetin treatment significantly reversed 464 DETs and enriched several signaling pathway (including apoptosis and p53 pathways). Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling staining and Annexin V staining revealed that quercetin treatment reduced cell apoptosis in renal tissues of Ang II-infused mice and in NRK-52E cells stimulated with Ang II. Furthermore, immunohistochemistry and western-blotting indicated that quercetin treatment alleviated the upregulation of p53, BaX, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II infused mice and NRK-52E cells stimulated with Ang II stimulation. Moreover, the molecular docking results indicated potential binding activity between quercetin-TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-induced mice and Ang II stimulated NERK-52E cell, and by targeting p53 may be one of the underlying mechanisms.

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Qingda Granule Attenuates Angiotensin II-Induced Renal Apoptosis and Activation of the p53 Pathway

Cited by 13 publications

References 40 publications

Dietary choline intake is necessary to prevent systems‐wide organ pathology and reduce Alzheimer's disease hallmarks

Dietary choline intake is necessary to prevent systems‐wide organ pathology and reduce Alzheimer's disease hallmarks

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer’s disease hallmarks

An integrated network pharmacology and RNA-seq approach for exploring the renal protection of quercetin on attenuating Ang II- induced cells apoptosis

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