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Oleanolic acid derivative isolated from Gardenia jasminoides var. radicans alleviates LPS-induced acute kidney injury in mice by reducing oxidative stress and inflammatory responses via the TLR4/NF-κB/NLRP3 signaling pathway

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Abstract

Acute kidney injury (AKI) is a frequent complication of sepsis with hallmarks including inflammation and oxidative stress. A large amount of oleanolic acid derivatives (TO) have been isolated from Gardenia jasminoides var. radicans, a traditional Chinese medicine with anti-inflammatory efficacy; thus, the aim of the present study was to evaluate the protective effects of TO on injury in a murine model of endotoxemic AKI. Kidney function, inflammation, oxidative stress, apoptosis, white blood cell count, TLR4/NF-κB/NLRP3 pathway involvement and metabolic profiling of the serum were evaluated. The results show that TO significantly ameliorated renal function in mice with LPS-induced AKI; 2-deoxy-D-glucose (2-DG) optical probe imaging indicated that TO markedly reduced the levels of inflammation; flow cytometry demonstrated that TO had an excellent antioxidant effect, regulating immune cells; Western blotting indicated that TO inhibited the TLR4/NF-κB/NLRP3 signaling pathway; and metabolic profiling of the serum also demonstrated the protective effects of TO on injury in a murine model of endotoxemic AKI. In summary, TO renoprotection involves the attenuation of LPS-induced renal inflammation and oxidative stress, which may be mediated via inhibition of the TLR4/NF-κB/NLRP3 signaling pathway.

Graphical abstract: Oleanolic acid derivative isolated from Gardenia jasminoides var. radicans alleviates LPS-induced acute kidney injury in mice by reducing oxidative stress and inflammatory responses via the TLR4/NF-κB/NLRP3 signaling pathway

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Article information


Submitted
22 Oct 2019
Accepted
15 Jan 2020
First published
15 Jan 2020

New J. Chem., 2020, Advance Article
Article type
Paper

Oleanolic acid derivative isolated from Gardenia jasminoides var. radicans alleviates LPS-induced acute kidney injury in mice by reducing oxidative stress and inflammatory responses via the TLR4/NF-κB/NLRP3 signaling pathway

M. Zeng, Y. Cao, R. Xu, Y. Wu, Y. Wang, Y. Zhang, X. Zheng and W. Feng, New J. Chem., 2020, Advance Article , DOI: 10.1039/C9NJ05294A

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