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The protective effect of puerarin-loaded mesoporous silicon nanoparticles on alcoholic hepatitis through mTOR-mediated autophagy pathway

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Abstract

Puerarin, a bioactive flavone compound isolated from Pueraria (Wild.), provides hepatoprotection by anti-inflammatory, anti-alcoholism, and regulating mechanistic target of rapamycin (mTOR). Building evidence suggests that the activation of mTOR reduces liver injuries associated with alcohol consumption and metabolism. However, the poor water solubility, low bioavailability, and short half-life of puerarin hinder its clinical application. The utility of mesoporous silicon nanoparticles (MSNs) can improve traditional Chinese medicine limitations. Stober methods were used to fabricate MSNs@Pue, and the size, zeta potentials and drug encapsulation efficiency were characterized by a series of analytical methods. IVIS Imaging System demonstrated liver-targeted bio-distribution, and then high-throughput sequencing, immunoproteomics and ultrastructure methods indicated autophagy related protective mechanism, followed by curative effect evaluation for the treatment efficacy. An acute-on chronic ethanol-drinking according to Gao-binge model induced alcoholic hepatitis (AH) pathology and resulted in hepatic hyper-autophagy, which was improved with MSNs@Pue administration (puerarin: 30 mM, 42 mg/kg; intravenously [i.v.]). Ethanol-fed mice were found to have increased expression of autophagy-related proteins (Atg3, Atg7, LC3 and p62). In contrast, MSNs@Pue administration significantly decreased the expression of these proteins and alleviated fatty droplets infiltration in damaged liver. Furthermore, acute-on-chronic ethanol feeding also resulted in the activiation of ERK activation and mTOR expression, which were reversed with MSNs@Pue administration and better than the usage of puerarin alone. Results point to MSNs@Pue mediated ERK/mTOR signaling pathway activation as a possible protective strategy to improve AH, which provides a strategy and evidence for treating liver disease using an MSN delivery system.

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Data availability

All data used to support the findings during the present study are available from the corresponding authors on reasonable request.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81570536, 82001946) and the Beijing Municipal Natural Science Foundation (No. 7214300).

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Authors and Affiliations

  1. Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China

    Xia-xia Zhang, Yan-fei Lang, Xin Li, Zheng Li & You-qing Xu

  2. Translational Medicine Center, Beijing Chest Hospital, Capital Medical University / Beijing Tuberculosis, Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China

    Hong-qian Chu

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  1. Xia-xia Zhang
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  2. Yan-fei Lang
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  3. Xin Li
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  4. Zheng Li
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Contributions

Xiaxia Zhang: formal analysis, investigation, methodology and writing-original draft. Yanfei Lang: Methdology. Xin Li and Zheng Li: software. Youqing Xu and Hongqian Chu: conceptualization, data curation project administration, supervision and writing-review&editing.

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Correspondence to You-qing Xu or Hong-qian Chu.

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Zhang, Xx., Lang, Yf., Li, X. et al. The protective effect of puerarin-loaded mesoporous silicon nanoparticles on alcoholic hepatitis through mTOR-mediated autophagy pathway. Biomed Microdevices 24, 37 (2022). https://doi.org/10.1007/s10544-022-00622-2

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