Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway

Huo, Changliang; Wang, Li; Wang, Qiuli; Yang, Yanbo; Chen, Bin

doi:10.3892/etm.2021.10282

Cited by 2 publications

(2 citation statements)

References 42 publications

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“…The expressions of PI3K and p-PI3K were significantly increased in the model group, ( p < 0.01), but significantly decreased after FSGD and NDQ treatment ( p < 0.05, Figures 8A–D ), compared with the model group. These similar results can be found in previous study ( Haitao et al, 2021 ; Huo et al, 2021 ).…”

Section: Resultssupporting

confidence: 93%

Effect of Fushengong Decoction on PTEN/PI3K/AKT/NF-κB Pathway in Rats With Chronic Renal Failure via Dual-Dimension Network Pharmacology Strategy

Luo

Wang

et al. 2022

Front. Pharmacol.

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Overview: The treatment of chronic renal failure (CRF) with traditional Chinese medicine has attracted much attention, but its mechanism is not clear. Network pharmacology is an effective strategy for exploring the interaction mechanisms between Chinese herbs and diseases, however, it still needs to be validated in cell and/or animal experiments due to its virtual screening characteristics. Herein, the anti-CRF mechanism of the Fushengong decoction (FSGD) was investigated using a dual-dimension network pharmacological strategy combined with in vivo experiment.Methods: The traditional Chinese medicine systems pharmacology (TCMSP) database (https://tcmspw.com) and UHPLC-MS/MS technology were used to identify the effective compounds of FSGD in theory and practice, such as quercetin, formononetin, and pachymic acid. The putative targets of FSGD and CRF were obtained from the Swisstarget prediction platform and the Genecards database, respectively. The common target pathways between FSGD and CRF were got from the dual-dimension network pharmacology analysis, which integrated the cross-common targets from the TCMSP components-Swisstarget-Genecards-Venn platform analysis in theory, and the UHPLC-MS/MS identified effective ingredients-Swisstarget screening, such as TNF and PI3K/AKT. Furthermore, system molecular determinations were used to prove the dual-dimension network pharmacology study through CRF rat models, which were constructed using adenine and treated with FSGD for 4 weeks.Results: A total of 121 and 9 effective compounds were obtained from the TCMSP database and UHPLC-MS/MS, respectively. After dual-dimension network pharmacology analysis, the possible mechanism of PTEN/PI3K/AKT/NF-κB pathway was found for FSGD in CRF. In vivo experiments indicated that FSGD can play a role in protecting renal function and reducing fibrosis by regulating the PTEN/PI3K/AKT/NF-κB pathway. These findings provide a reference for FSGD in CRF.Conclusion: Based on the theoretical and practical dual-dimension network pharmacology analysis for FSGD in CRF, the possible molecular mechanism of PTEN/PI3K/AKT/NF-κB was successfully predicted, and these results were verified by in vivo experiments. In this study, the dual-dimension network pharmacology was used to interpret the key signal pathway for FSGD in CRF, which also proved to be a smart strategy for the study of effective substances and pharmacology in FSGD.

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Section: Resultssupporting

confidence: 93%

Effect of Fushengong Decoction on PTEN/PI3K/AKT/NF-κB Pathway in Rats With Chronic Renal Failure via Dual-Dimension Network Pharmacology Strategy

Luo

Wang

et al. 2022

Front. Pharmacol.

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“…The phosphorylation of pathway proteins was greatly enhanced in unsuccessful AVFs, indicating that the process was active. Huo et al 22 investigated the PI3K/Akt signaling pathway in AVFs, as well as the survival and migration of VSMCs, but did not discuss whether c-kit was linked to pathway activation. The majority of our current understanding of neointimal cells in AVFs is derived from extrapolations of arterial neointima in non-AVF systems.…”

Section: Discussionmentioning

confidence: 99%

Elevated c-kit expression in failed autologous arteriovenous fistulas in end-stage renal disease patients

Jia

et al. 2022

J Vasc Access

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Background: Serum stem cell factor is elevated in end-stage renal disease (ESRD) patients. This study aimed to investigate the expression of the c-kit receptor, which is the specific membrane receptor of stem cell factor, in failed autologous arteriovenous fistulas (AVFs) in end-stage renal disease patients. Methods: A total of 14 ESRD patients with initial AVFs creation and 16 ESRD patients with reconstruction were enrolled in this study. Hematoxylin and eosin (H&E) and elastic Verhoeff-Van Gieson (EVG) staining were used for histomorphometric analyses. Immunohistochemistry was used to examine the expression of c-kit in the intima, and a correlation analysis was performed with the intimal area and the percentage of area stenosis. A double-label immunofluorescence method was used to explore the colocalization of c-kit with α-smooth muscle actin (α-SMA) and CD31. The expression of c-kit and the related PI3K/Akt signaling axis, including PI3K, P-PI3K, Akt, P-Akt473, P-Akt308, and mTOR, was measured by western blotting. Results: Internal elastic lamina (IEL) area, intimal area, percentage of area stenosis, and average optical density (AOD) of c-kit in the intima were significantly higher in the failed group than in the preoperative group ( p ⩽ 0.001). The AOD of c-kit in the intima was positively correlated with the intimal area and the percentage of stenosis (intimal area: R = 0.744, p < 0.001; the percentage of stenosis: R = 0.923, p < 0.001). C-kit colocalized with α-SMA but not with CD31 in studies of c-kit target cells. Moreover, the levels of c-kit and P-PI3K, P-Akt473 and mTOR in the PI3K/Akt axis were also higher in the failed group than in the initial group ( p < 0.05). Conclusions: C-kit and related proteins associated with the PI3K/Akt pathway were elevated in failed AVFs among ESRD patients and that the expression level of c-kit in the intima correlates with the degree of AVF stenosis.

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Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway

Cited by 2 publications

References 42 publications

Effect of Fushengong Decoction on PTEN/PI3K/AKT/NF-κB Pathway in Rats With Chronic Renal Failure via Dual-Dimension Network Pharmacology Strategy

Effect of Fushengong Decoction on PTEN/PI3K/AKT/NF-κB Pathway in Rats With Chronic Renal Failure via Dual-Dimension Network Pharmacology Strategy

Elevated c-kit expression in failed autologous arteriovenous fistulas in end-stage renal disease patients

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