Rutin alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

Chen, Shengsong; Bai, Yu; Xia, Jingen; Zhang, Yi; Zhan, Qingyuan

doi:10.1016/j.isci.2023.107866

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…Our previous study confirmed that rutin alleviates VILI in mice by inhibiting NLRP3 inflammasome activation (S. Chen, Bai, et al, 2023).…”

Section: Metabolomic Analysissupporting

confidence: 67%

“…Chen et al, 2014;Huang et al, 2016). Our previous study showed that rutin alleviates VILI in mice by inhibiting the inflammatory response (S. Chen, Bai, et al, 2023). In this study, the mice were intraperitoneally injected with 100 μmol/kg rutin according to previous research to further clarify the mechanism of action of rutin in VILI (S. Chen, Bai, et al, 2023;Huang et al, 2016;Yeh et al, 2014).…”

Section: Discussionmentioning

confidence: 92%

“…Rutin (MCE, HY-N0148, USA) whose purity is 95.12% was selected and the chemical structure and characterization by HPLC is in Figure S1. Rutin was dissolved in DMSO, and the mice were intraperitoneally injected with rutin (10, 50 and 100 μmol/kg) to determine the optimal concentration according to the previous studies (S. Chen, Bai, et al, 2023;Huang et al, 2016;Yeh et al, 2014). Then, the mice were randomized into the VILI + rutin group or the rutin group.…”

Section: Mouse Model Of Vili and Rutin Treatmentmentioning

confidence: 99%

“…Rutin is a powerful phenolic antioxidant that has various pharmacological properties, including anti-inflammatory, antibacterial, antioxidant, antiapoptotic, detoxification, lipid-lowering, vasodilation and antitumor effects (Bispo da Silva et al, 2017;Khajevand-Khazaei et al, 2018;Muvhulawa et al, 2022;Yeh et al, 2014). Our previous study showed that rutin alleviates VILI by inhibiting NLRP3 inflammasome activation (s. Chen, Bai, et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

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Rutin targets AKT to inhibit ferroptosis in ventilator‐induced lung injury

Chen,

Li,

Xiao

et al. 2024

Phytotherapy Research

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Our previous research confirmed that rutin reduced ventilator‐induced lung injury (VILI) in mice. Ferroptosis has been reported to participate in the pathogenic process of VILI. We will explore whether rutin inhibits ferroptosis to alleviate VILI. A mouse model of VILI was constructed with or without rutin pretreatment to perform a multiomics analysis. Hematoxylin–eosin (HE) staining and transmission electron microscopy were used to evaluate lung injury in VILI mice. Dihydroethidium (DHE) staining and the malondialdehyde (MDA) and superoxide dismutase (SOD) levels were detected. Molecular docking was performed to determine the binding affinity between rutin and ferroptosis‐related proteins. Western blot analysis, real‐time PCR (RT‐PCR) and immunohistochemical (IHC) staining were conducted to detect the expression levels of GPX4, XCT, ACSL4, FTH1, AKT and p‐AKT in lung tissues. Microscale thermophoresis (MST) was used to evaluate the binding between rutin and AKT1. Transcriptomic and proteomic analyses showed that ferroptosis may play a key role in VILI mice. Metabolomic analysis demonstrated that rutin may affect ferroptosis via the AKT pathway. Molecular docking analysis indicated that rutin may regulate the expression of ferroptosis‐related proteins. Moreover, rutin upregulated GPX4 expression and downregulated the expression of XCT, ACSL4 and FTH1 in the lung tissues. Rutin also increased the ratio of p‐AKT/AKT and p‐AKT expression. MST analysis showed that rutin binds to AKT1. Rutin binds to AKT to activate the AKT signaling pathway, contributing to inhibit ferroptosis, thus preventing VILI in mice. Our study elucidated a possible novel strategy of involving the use of rutin for preventing VILI.

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“…Our previous study confirmed that rutin alleviates VILI in mice by inhibiting NLRP3 inflammasome activation (S. Chen, Bai, et al, 2023).…”

Section: Metabolomic Analysissupporting

confidence: 67%

Section: Discussionmentioning

confidence: 92%

Section: Mouse Model Of Vili and Rutin Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rutin targets AKT to inhibit ferroptosis in ventilator‐induced lung injury

Chen,

Li,

Xiao

et al. 2024

Phytotherapy Research

Self Cite

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“…These effects are mediated through the NF-κB [ 25 ] and MAPKs pathways, resulting in anti-inflammatory effects on Klebsiella-infected mice [ 26 ]. Quercetin [ 27 , 28 ], rutin [ 29 , 30 ], and kaempferide [ 31 ], all flavonoids, have anti-inflammatory properties to ameliorates acute lung injury. Khazdair Mohammad et al demonstrated that quercetin can reduce the levels of reactive oxygen species, as well as the expression of inducible nitric oxide synthase and pro-inflammatory mediators such as TNF-α, IL-1α, IL-1β, IL-6, IL-10, and IL-12.…”

Section: Discussionmentioning

confidence: 99%

Discovery of the Active Compounds of the Ethyl Acetate Extract Site of Ardisia japonica (Thunb.) Blume for the Treatment of Acute Lung Injury

Sun,

Liu,

Zhao

et al. 2024

Molecules

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The objective of this study was to identify and evaluate the pharmacodynamic constituents of Ardisiae Japonicae Herba (AJH) for the treatment of acute lung injury (ALI). To fully analyze the chemical contents of various extraction solvents (petroleum ether site (PE), ethyl acetate site (EA), n-butanol site (NB), and water site (WS)) of AJH, the UPLC–Orbitrap Fusion–MS technique was employed. Subsequently, the anti-inflammatory properties of the four extracted components of AJH were assessed using the lipopolysaccharide (LPS)-induced MH-S cellular inflammation model. The parts that exhibited anti-inflammatory activity were identified. Additionally, a technique was developed to measure the levels of specific chemical constituents in the anti-inflammatory components of AJH. The correlation between the “anti-inflammatory activity” and the constituents was analyzed, enabling the identification of a group of pharmacodynamic components with anti-inflammatory properties. ALI model rats were created using the tracheal drip LPS technique. The pharmacodynamic indices were evaluated for the anti-inflammatory active portions of AJH. The research revealed that the PE, EA, NB, and WS extracts of AJH included 215, 289, 128, and 69 unique chemical components, respectively. Additionally, 528 chemical components were discovered after removing duplicate values from the data. The EA exhibited significant anti-inflammatory activity in the cellular assay. A further analysis was conducted to determine the correlation between anti-inflammatory activity and components. Seventeen components, such as caryophyllene oxide, bergenin, and gallic acid, were identified as potential pharmacodynamic components with anti-inflammatory activity. The pharmacodynamic findings demonstrated that the intermediate and high doses of the EA extract from AJH exhibited a more pronounced effect in enhancing lung function, blood counts, and lung histology in a way that depended on the dosage. To summarize, when considering the findings from the previous study on the chemical properties of AJH, it was determined that the EA contained a group of 13 constituents that primarily contributed to its pharmacodynamic effects against ALI. The constituents include bergenin, quercetin, epigallocatechingallate, and others.

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