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Luteolin-7-O-rutinoside from Pteris cretica L. var. nervosa attenuates LPS/D-gal-induced acute liver injury by inhibiting PI3K/AKT/AMPK/NF-κB signaling pathway

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Abstract

Pteris cretica L. var. nervosa is one of the most well-known Chinese medicines. Although it is widely used to treat jaundice hepatitis, the main ingredient for its treatment was not thoroughly explored until recently. Essentially, the purpose of this study is to find the monomer compound in Pteris cretica L. var. nervosa, which is most likely to be effective in treating liver injury. Through the model of LPS/D-gal-induced liver injury in mice, the best therapeutic site of the total extract was explored, the chemical components of the parts with the best therapeutic effect were separated, a total of 10 flavonoids were isolated, and the RAW264.7 cells induced by LPS were used as the experimental model to explore the preliminary anti-inflammatory activity of NO production in vitro. Finally, the anti-inflammatory activity and the highest content in this plant Luteolin-7-O-rutinoside (LUT) were selected, as the object of study in vivo. It was found that LUT could not only reduce alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, but also significantly reduce the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and inhibit PI3K/AKT/AMPK/NF-κB pathway. In addition, LUT can increase levels of SOD and GSH to reduce oxidative stress. It has an obvious therapeutic effect on acute liver injury induced by LPS/D-gal in mice. Therefore, infer LUT is a functional substance in Pteris cretica L. var. nervosa.

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Funding

This work was supported financially by National Key R&D Program of China (2019YFC1712304), National Natural Science Foundations of China under Grant (81860684), Science and Technology Research Project of Education Department of Jiangxi Province (GJJ190689), and Key projects of Natural Science Foundation of Jiangxi Province (20212ACB206007).

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Contributions

Z.W.X.—isolation and purification. Q.W. and Z.W.X.—identify the structure. Z.W.X and Y.S.C.—acute liver injury evaluation and animal experiment. J.H.W. and L.Y.S. processed the data. Z.W.X—writing original draft preparation. S.L.Y.—writing review and editing. Y.L.F. and Q.W.—supervision. All data were generated in-house and no paper mill was used.

Corresponding author

Correspondence to Yulin Feng.

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Animal experiments were conducted according to the regulations of the Institute Animal Ethics Committee (approval number: SCXK (Xiang) 2019-0004).

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Not applicable.

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The authors declare no competing interests.

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Xiong, Z., Cui, Y., Wu, J. et al. Luteolin-7-O-rutinoside from Pteris cretica L. var. nervosa attenuates LPS/D-gal-induced acute liver injury by inhibiting PI3K/AKT/AMPK/NF-κB signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 395, 1283–1295 (2022). https://doi.org/10.1007/s00210-022-02266-8

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