Guanosine and uridine alleviate airway inflammation via inhibition of the MAPK and NF-κB signals in OVA-induced asthmatic mice

Luo, Yujiao; Hai, Chen; Huang, Ridong; Wu, Qiong; Li, Ying; He, Yang

doi:10.1016/j.pupt.2021.102049

Cited by 23 publications

(10 citation statements)

References 61 publications

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“…Guanosine, an endogenous purine nucleoside is essential for metabolism ( 31 ). Recently, it is reported that guanosine has positive inotropic effects in isolated ventricular muscle and atria ( 32 ), and alleviates inflammation of airway ( 33 ), spinal cord after acute injury ( 34 ), brain after traumatic injury ( 35 ) and intestinal inflammation ( 36 ). Deoxynucleoside can reverse the metabolism of transcriptase inhibitors in perfused heart and isolated mitochondria ( 37 ), and had the therapeutic efficacy for Tk2 deficiency ( 38 ).…”

Section: Resultsmentioning

confidence: 99%

Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice

Wang

Chen

Zhang

et al. 2022

Front. Cardiovasc. Med.

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Myocardial infarction (MI) is the major cause of mortality around the world. We recently demonstrated that chick early amniotic fluid (ceAF) can effectively rescue ischemic heart injury, indicating that it has a therapeutic function in MI. However, its functional components and the underlying mechanisms remain to be clarified. Here, we demonstrated that a fraction of ceAF, peak 8 (P8), had a protective effect on acute MI. P8 significantly decreased cardiomyocyte cross-sectional areas and cardiomyocyte apoptosis in MI mice. Using a human embryonic stem cell-derived cardiomyocyte model, which was subjected to hypoxia and reoxygenation, mimicking MI state, we found that P8 treatment reduced apoptosis and reversed myocardial contractility. Mechanistically, P8 improved cardiac function by inhibiting NF-κB signaling and downregulating inflammatory cytokine expression. Using mass spectrometry, we identified that guanosine and deoxynucleoside were the main functional components of P8 that suppressed the inflammatory response in human embryonic stem cell-derived cardiomyocytes. Collectively, our data suggest that specific components from ceAF are promising therapeutic agents for ischemic heart injury and could be a potential supplement to current medications for MI.

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Section: Resultsmentioning

confidence: 99%

Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice

Wang

Chen

Zhang

et al. 2022

Front. Cardiovasc. Med.

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“…Moreover, administration of guanosine or uridine reduced cytokines such as IL-4, IL-6, IL-13, and ovalbumin-specific IgE in the lungs of OVA-challenged asthmatic mice. In addition, the production of IL-6 and the expression of key molecules in the MAPK and NF-κB pathways were decreased by uridine and guanosine in lipopolysaccharide/IFN-γ-induced THP-1 cells and lung tissues [ 37 ]. In a dinitrobenzene sulfonic acid-induced colitis model, guanosine lowered IL-1β, IL-6, and TNF-α mRNA levels and downregulated the expression of NF-κB p65 and the levels of ROS and nitrite [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Amauroderma rugosum Extract Suppresses Inflammatory Responses in Tumor Necrosis Factor Alpha/Interferon Gamma-Induced HaCaT Keratinocytes

Shiu

Zheng

et al. 2022

Molecules

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Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum has been previously reported, it is not known whether the aqueous extract has a similar effect. In addition, the effect of Amauorderma rugosum extract on skin has never been explored. Therefore, the objectives of the present study were to evaluate the anti-inflammatory effects of the aqueous extract of Amauroderma rugosum on HaCaT keratinocytes, to explore its mechanisms of action, and to study the possible active ingredients involved. The results showed that the aqueous extract of Amauroderm rugosum at a concentration of 1.5 mg/mL was non-toxic to HaCaT cells and inhibited the release of cytokine interleukin-1β, and chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-stimulated HaCaT cells. Amauroderma rugosum extract reduced the intracellular levels of reactive oxygen species. In addition, Amauroderma rugosum extract reduced the total protein expression of nuclear factor-kappa B (NF-κB) and B-cells inhibitor alpha in HaCaT keratinocytes and inhibited the phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in TNF-α- and INF-γ-stimulated HaCaT keratinocytes. Chemical analysis revealed that the aqueous extract of Amauroderma rugosum contains polysaccharides, triterpenes, and phenolic compounds. Anti-inflammatory compounds, such as gallic acid, guanosine, and uridine, were also present. The anti-inflammatory effect of Amauroderma rugosum could be mimicked by a combination of gallic acid, guanosine, and uridine. In conclusion, our study suggests that the aqueous extract of Amauroderma rugosum exerts anti-inflammatory effects on keratinocytes through its antioxidant and inhibitory effects on MEK/ERK-, Akt/mTOR-, and NF-κB-dependent signaling pathways.

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“…In this experiment, semaglutide significantly reduced the expression of proinflammatory cytokines (IL-6, IL-1β and TNF-α). 3 , 16 , 21 , 32 , 60 Previous studies showed that oxidative stress response will result in accumulation of reactive oxygen and lipids deposit in tissue. Furthermore, lipid peroxidation can lead to final production of MDA, which subsequently cause severe cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice

Chen¹,

Chen²,

Ren³

et al. 2022

DDDT

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Semaglutide, a new long-acting glucagon-like peptide-1 analogue, has shown benefits for renal diseases, but its direct role on kidney metabolism under obesity remains unclear. The study aims to elucidate the protective effect and metabolic modulation mechanism of semaglutide on obesity-related kidney injury. Methods: Male C57BL/6J mice were divided into control and obesity groups. Mice in the obesity group had a high-fat diet and were treated with or without semaglutide (30nmol/kg/day). The study assayed blood biochemistry and then evaluated renal pathological injury through Periodic Acid-Schiff staining and electron microscopy. Metabolomics was utilized to analyze obesity-related metabolites in kidney samples. Results: Semaglutide significantly improved glucose homeostasis, insulin resistance, and kidney injury in obese mice. We successfully identified 377 altered metabolites (P<0.05). It was suggested that semaglutide directly improved oxidative stress and inflammation-related metabolites such as nicotinamide adenine dinucleotide (NAD + ) and adenosine in the kidney of obese mice, which have not been documented in obesity-related kidney injury. Relevant enriched pathways were included phospholipids and lysophospholipids metabolism, purine metabolism, NAD + metabolism, and insulin resistance-related metabolism. They could serve as potential targets for intervention of obesity-related kidney injury. Conclusion:Our study revealed the metabolomics-based renoprotective mechanism of semaglutide in obese mice for the first time. The innovation lied in the identified metabolites such as NAD + and adenosine targeted by semaglutide, which have not been documented in obesity-related kidney injury. Semaglutide may be a promising therapy for obesity-related kidney diseases.

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Guanosine and uridine alleviate airway inflammation via inhibition of the MAPK and NF-κB signals in OVA-induced asthmatic mice

Cited by 23 publications

References 61 publications

Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice

Chick early amniotic fluid component improves heart function and protects against inflammation after myocardial infarction in mice

Amauroderma rugosum Extract Suppresses Inflammatory Responses in Tumor Necrosis Factor Alpha/Interferon Gamma-Induced HaCaT Keratinocytes

Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice

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