3‐<i>O</i>‐trans‐caffeoyloleanolic acid improves acute lung injury via anti‐inflammation and antioxidative stress‐involved PI3K/AKT pathway

Huang, Jianhua; Nong, Xueping; Chen, Yanling; Zhang, Aimei; Chen, Lerong

doi:10.1111/cbdd.13856

Cited by 11 publications

(6 citation statements)

References 31 publications

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“…In some studies, oxidative stress has been shown to decrease pAkt in, for example, uterine and mesangial cells [32,33], whereas yet other studies have shown that oxidative stress increases pAkt in alveolar and human THP1 macrophages [34][35][36]. However, to our knowledge, our study is the first to demonstrate that oxidative stress-induced meta-and ortho-Tyr increase pAkt in macrophages independently of insulin effects.…”

Section: Discussioncontrasting

confidence: 51%

Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines

Csurgyók,

Sütő,

Engelmann

et al. 2023

Preprint

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In obesity, white adipose tissue expresses inflammatory cytokines leading to insulin resistance. Non-physiological meta-tyrosine and ortho-tyrosine (meta-Tyr and ortho-Tyr), produced from phenylalanine by free radicals, may contribute to the development of insulin resistance. The resulting insulin resistance may have a significant impact on macrophage function. In this study we aim to investigate microscopically the effect of meta- and ortho-Tyr on insulin sensitivity and M1/M2 polarization of macrophages using Akt phosphorylation and the arginase 1/iNOS ratio. Macrophage cell lines were cultured in media containing para-, meta- or ortho-Tyr, 5 mmol/L or 25 mmol/L glucose (para25-Tyr group) and treated with insulin. Para25, meta- and ortho-Tyr increased pAkt levels and decreased the arginase 1/iNOS ratio in macrophages in the absence of insulin. In the case of physiological para-tyrosine treatment, insulin increased the amount of pAkt and decreased the arginase 1/iNOS ratio. Both meta- and ortho-Tyr treatment were able to abolish or reverse the insulin’s increasing effect on pAkt and the decreasing effect on arginase 1/iNOS ratio. Our results suggest that non-physiological tyrosine isomers may affect the insulin signaling of macrophages and influence their M1/M2 polarization.

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Section: Discussioncontrasting

confidence: 51%

Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines

Csurgyók,

Sütő,

Engelmann

et al. 2023

Preprint

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“…The 46 potential targets between PAE targets and ALI ones were used to further analyze the signaling pathways involved in the prevention of ALI by PAE. Combined some papers find that PI3K/Akt signaling pathway was mostly associated with LPS-induced ALI [47][48][49]. In membrane lipid metabolism, PI3K phosphorylates PI-4-P (PIP) produce PI-3,4-P 2 (PIP2) and PIP2 produces PI-3,4,5-P 3 (PIP3).…”

Section: Discussionmentioning

confidence: 99%

“…However, one may notice that the research reports on the PI3K/Akt signaling pathway were controversial in the studies of LPS-induced acute lung injury (ALI). There is still no clear result on whether the activation or inhibition of the PI3K/Akt signaling pathway on the protective effect of ALI [47][48][49][57][58][59]. Readers may find the details about the relationship between PI3K/Akt signaling pathway and ALI in the Additional file.…”

Section: Discussionmentioning

confidence: 99%

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Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

et al. 2023

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Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

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“…3,4 In the experimental animal model of ALI/ARDS, lipopolysaccharide (LPS) can trigger systemic inflammation to release pro-inflammatory mediators, 5,6 such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), leading to increased accumulation of reactive oxygen species (ROS). 7 In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content are related to LPS-induced oxidative stress. 8 Previous reports have revealed that inhibiting inflammation and oxidative stress can mitigate LPS-triggered ALI/ ARDS.…”

Section: Introductionmentioning

confidence: 99%

The impacts of SphK1 on inflammatory response and oxidative stress in LPS-induced ALI/ARDS

Chao-shun

Wang

2023

Eur J Inflamm

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As severe conditions, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) threaten human health. Inflammation and oxidative stress play a vital role in the pathogenesis of ALI/ARDS. Sphingosine kinase 1 (SphK1) significantly contributes to mediating inflammatory responses. Nevertheless, the impact of SphK1 on lipopolysaccharide (LPS)-triggered ALI/ARDS remains largely undetermined. In our current work, we explored the impact of SphK1 on ALI/ARDS using a mouse model. We studied whether it could reduce LPS-triggered inflammatory response and oxidative stress by suppressing SphK1 in ALI/ARDS. The mice were treated with the inhibitor of SphK1 (N,N-dimethylsphingosine, DMS) before intraperitoneal injection of LPS. Moreover, we assessed the survival rate, and several parameters, such as the lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and the release of inflammatory cytokines. Western blotting analysis was adopted to evaluate the levels of phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT) pathways. We showed that the inhibitor of SphK1 not only ameliorated LPS-stimulated lung histopathological changes and W/D ratio of lung tissue but also elevated the survival rate, the SOD activity and decreased the MDA content, MPO activity, interleukin-6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ) production by regulating the PI3K/AKT signaling pathway in lung tissue. Taken together, SphK1 played an essential role in inflammatory responses and oxidative stress. The underlying mechanism might be linked to the activation and up-regulation of the PI3K/AKT signaling pathway in LPS-triggered ALI/ARDS.

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3‐O‐trans‐caffeoyloleanolic acid improves acute lung injury via anti‐inflammation and antioxidative stress‐involved PI3K/AKT pathway

Cited by 11 publications

References 31 publications

Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines

Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines

Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

The impacts of SphK1 on inflammatory response and oxidative stress in LPS-induced ALI/ARDS

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