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Hepatoprotective effects of baicalein against liver ischemia-reperfusion injury and partial hepatectomy in a rat model

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Abstract

Background

Baicalein is the main active flavonoid in Scutellariae Radix and is included in shosaikoto, a Kampo formula used for treating hepatitis and jaundice. However, little is known about its hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI), a severe clinical condition directly caused by interventional procedures. We aimed to investigate the hepatoprotective effects of baicalein against HIRI and partial hepatectomy (HIRI + PH) and its potential underlying mechanisms.

Methods and results

Male Sprague-Dawley rats received either baicalein (5 mg/kg) or saline intraperitoneally and underwent a 70% hepatectomy 15 min after hepatic ischemia. After reperfusion, liver and blood samples were collected. Survival was monitored 30 min after hepatic ischemia and hepatectomy. In interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes, the influence of baicalein on inflammatory mediator production and the associated signaling pathway was analyzed. Baicalein suppressed apoptosis and neutrophil infiltration, which are the features of HIRI + PH treatment-induced histological injury. Baicalein also reduced the mRNA expression of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). In addition, HIRI + PH treatment induced liver enzyme deviations in the serum and hypertrophy of the remnant liver, which were suppressed by baicalein. In the lethal HIRI + PH treatment group, baicalein significantly reduced mortality. In IL-1β-treated rat hepatocytes, baicalein suppressed TNF-α and chemokine mRNA expression as well as the activation of nuclear factor-kappa B (NF-κB) and Akt.

Conclusions

Baicalein treatment attenuates HIRI + PH-induced liver injury and may promote survival. This potential hepatoprotection may be partly related to suppressing inflammatory gene induction through the inhibition of NF-κB activity and Akt signaling in hepatocytes.

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No datasets were generated or analysed during the current study.

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Acknowledgements

We thank Editage (www.editage.com) for the English language editing and Kyodo Byori (Kobe, Japan) for staining the liver specimens.

Funding

This work was supported by JSPS KAKENHI Grant Numbers 19K18370, 19KK0413, 21K09032, and 21K08697.

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Author notes

  1. Tetsuya Okuyama and Richi Nakatake contributed equally to this study.

Authors and Affiliations

  1. Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, 573-1010, Osaka, Japan

    Tetsuya Okuyama, Richi Nakatake, Morihiko Ishizaki, Hidesuke Yanagida, Hiroaki Kitade & Mitsugu Sekimoto

  2. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, 525-8577, Shiga, Japan

    Kentaro Ito & Mikio Nishizawa

  3. Department of Innovative Food Sciences, School of Food Sciences and Nutrition, Mukogawa Women’s University, 6-46 Ikebiraki-cho, Nishinomiya, 663-8558, Hyogo, Japan

    Katsuhiko Yoshizawa

  4. Faculty of Pharmacy, Daiichi University of Pharmacy, 22-1 Tamagawa-machi, Minami-ku, Fukuoka, 815-8511, Fukuoka, Japan

    Yukinobu Ikeya

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  1. Tetsuya Okuyama
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Contributions

TO and RN participated in study design, data acquisition, statistical analysis, and manuscript drafting. KI contributed to data acquisition. KY and MN supervised the study and provided advice on drafting the manuscript. MI, HY, and HK assisted with the data collection and analysis. YI and MS provided advice regarding protocol development and assisted with study design. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Richi Nakatake.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Approval was granted by the Animal Care Committee of Kansai Medical University (Osaka, Japan) (approval no. 22–039 and no. 22–040).

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The authors declare no competing interests.

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Okuyama, T., Nakatake, R., Ito, K. et al. Hepatoprotective effects of baicalein against liver ischemia-reperfusion injury and partial hepatectomy in a rat model. Mol Biol Rep 51, 643 (2024). https://doi.org/10.1007/s11033-024-09548-9

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