Astringin protects LPS-induced toxicity by suppressing oxidative stress and inflammation via suppression of PI3K/AKT/NF-κB pathway for pediatric acute lung injury

Wang, Ling; Jiang, Shanshan; Li, Xiaoxiao; Lin, Tingting; Qin, Tao

doi:10.1007/s00210-023-02439-z

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…Previous studies have shown that the expression of phosphorylated PI3K, AKT, and NF-κB is upregulated in LPS-induced ALI, and the upregulation of phosphorylation markers is ameliorated after drug treatment. 59,60 In our study, we observed that pretreatment with CAP effectively mitigated lung injury induced by LPS, as evidenced by reductions in pulmonary edema and inflammatory cell infiltration. Furthermore, increased levels of proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, are often associated with a poor prognosis in ALI patients.…”

Section: Discussionsupporting

confidence: 50%

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Hu,

Liu,

Wang

et al. 2024

JIR

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Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI. Methods: The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPSinduced autophagy. Results: Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression. Conclusion: Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.

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Section: Discussionsupporting

confidence: 50%

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Hu,

Liu,

Wang

et al. 2024

JIR

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“…Recent studies have demonstrated that ROS could activate NF-κB, thereby promoting inflammatory responses and exacerbating tissue damage [ 36 ]. Consequently, antioxidant medications can ameliorate excessive inflammatory responses while concurrently reducing oxidative stress within the body, thus facilitating tissue repair [ 37 ]. Similarly, the Nrf2/HO-1 pathway not only eliminates ROS but also effectively regulates inflammatory responses [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

The Extracts Derived from Artemisia japonica Thunb. Leaves Mitigate Oxidative Stress and Inflammatory Response Induced by LPS in RAW264.7 Cells through Modulation of the Nrf2/HO-1 Signaling Pathway

Ye,

Li,

Chen

et al. 2024

Molecules

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Artemisia japonica Thunb. has been used as a traditional Chinese medicine and a vegetable for thousands of years in China. However, there are few reports on the chemical composition and biological activity of its leaves. Thus, this study aimed to evaluate the chemical composition, antioxidant and anti-inflammatory effects of water extracts of A. japonica leaves and their underlying mechanisms. A total of 48 compounds were identified in the water extract using UPLC-QTOF-MS2 analysis, with phenolic acids, particularly chlorogenic acid compounds, being the predominant components. The ethyl acetate fraction (EAF) contained most of the total phenolic content (385.4217 mg GAE/g) and displayed superior antioxidant capacity with the IC50DPPH•, IC50ABTS•+, and OD0.5reducing power at 10.987 μg/mL, 43.630 μg/mL and 26.883 μg/mL, respectively. Furthermore, EAF demonstrated potent antioxidant and anti-inflammatory effects in LPS-induced RAW264.7 cells by upregulating the Nrf2/HO-1 signal pathway. These findings highlight that A. japonica leaves possess remarkable abilities to mitigate inflammation and oxidative stress, suggesting their potential utilization as medicinal agents and food additives for promoting human health.

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“…Acute lung injury (ALI) is a continuum of lung alterations caused by various disorders, such as pneumonia (Sheehan et al, 2022) and asthma (Ohira et al, 2023). ALI progresses rapidly and poses substantial risks, particularly in children (Wang, Jiang, et al, 2023). Inflammatory infiltration and surfactant dysfunction are considered the primary triggers in the development of ALI (Kolomaznik et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

Chen,

Feng

et al. 2024

Biomedical Chromatography

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Qingxuan Zhike granules (QXZKG), a traditional Chinese patent medication, has shown therapeutic potential against acute lung injury (ALI). However, the precise mechanism underlying its lung‐protective effects requires further investigation. In this study, integrated network pharmacology, molecular docking, and lipidomics were used to elucidate QXZKG's regulatory effect on lipid metabolism in lipopolysaccharide‐induced ALI. Animal experiments were conducted to substantiate the efficacy of QXZKG in reducing pro‐inflammatory cytokines and mitigating pulmonary pathology. Network pharmacology analysis identified 145 active compounds that directly targeted 119 primary targets of QXZKG against ALI. Gene Ontology function analysis emphasized the roles of lipid metabolism and mitogen‐activated protein kinase (MAPK) cascade as crucial biological processes. The MAPK1 protein exhibited promising affinities for naringenin, luteolin, and kaempferol. Lipidomic analysis revealed that 12 lipids showed significant restoration following QXZKG treatment (p < 0.05, FC >1.2 or <0.83). Specifically, DG 38:4, DG 40:7, PC O‐40:8, TG 18:1_18:3_22:6, PI 18:2_20:4, FA 16:3, FA 20:3, FA 20:4, FA 22:5, and FA 24:5 were downregulated, while Cer 18:0;2O/24:0 and SM 36:1;2O/34:5 were upregulated in the QXZKG versus model groups. This study enhances our understanding of the active compounds and targets of QXZKG, as well as the potential of lipid metabolism in the treatment of ALI.

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Astringin protects LPS-induced toxicity by suppressing oxidative stress and inflammation via suppression of PI3K/AKT/NF-κB pathway for pediatric acute lung injury

Cited by 4 publications

References 52 publications

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

The Extracts Derived from Artemisia japonica Thunb. Leaves Mitigate Oxidative Stress and Inflammatory Response Induced by LPS in RAW264.7 Cells through Modulation of the Nrf2/HO-1 Signaling Pathway

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

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