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Gastrodin Alleviates Acetaminophen-Induced Liver Injury in a Mouse Model Through Inhibiting MAPK and Enhancing Nrf2 Pathways

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Abstract

Gastrodin is a major active phenolic glycoside extract from Gastrodia elata, an important herb used in traditional medicine. Previous research has reported that gastrodin possesses anti-inflammatory and anti-oxidant properties. Therefore, we aimed to investigate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in a mouse model. Mice included in this study were intraperitoneally administered with a hepatotoxic APAP dose (300 mg/kg). At 30 min after APAP administration, gastrodin was intraperitoneally injected at concentrations of 0, 15, 30, and 45 mg/kg. Then, all mice were sacrificed at 16 h after APAP injection for further analysis. The results showed that gastrodin treatment ameliorated acute liver injury caused by APAP, as indicated by serum alanine aminotransferase level, hepatic myeloperoxidase activity, and cytokine (TNF-α, IL-1β, and IL-6) production. It also significantly decreased hepatic malondialdehyde activity but increased superoxide dismutase activity. In addition, gastrodin decreased ERK/JNK MAPK expression but promoted Nrf2 expression. These results demonstrated that gastrodin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity via amelioration of the inflammatory response and oxidative stress, inhibition of ERK/JNK MAPK signaling pathways, and activation of Nrf2 expression levels.

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Funding

This work was supported in part by grants from the National Science Council (MOST 108–2314-B-182A-059-MY2) and Chang Gung Memorial Hospital (CMRPG3J1561-2) to Fu-Chao Liu and Chang Gung Memorial Hospital (CORPG3G0601) to Chia-Chih Liao.

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  1. Department of Anesthesiology, Chang Gung Memorial Hospital, No. 5, Fushing 1st Rd, Gueishan, Taoyuan, 33305, Taiwan

    Chia-Chih Liao, Huang-Ping Yu, An-Hsun Chou, Hung-Chen Lee, Li-Min Hu & Fu-Chao Liu

  2. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chia-Chih Liao, Huang-Ping Yu, An-Hsun Chou, Hung-Chen Lee & Fu-Chao Liu

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  1. Chia-Chih Liao
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Contributions

C.C.L., H.P.Y., and F.C.L. conceived and designed this study. A.H.C. and H.C.L. carried out experiments. C.C.L. and L.M.H. collected and analyzed data. L.M.H. performed statistical analysis. C.C.L. and H.P.Y. wrote the manuscript, which was critically reviewed and revised by H.C.L. and F.C.L. All authors read and approved the final manuscript.

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Correspondence to Fu-Chao Liu.

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All procedures carried out in this study were approved by the Institutional Animal Care and Use Committee of Chang Gung Memorial Hospital (Taoyuan, Taiwan) (No. 2019091102). All animal experiments were performed according to the guidelines of the Animal Welfare Act and the Guide for Care and Use of Laboratory Animals from the National Institutes of Health.

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Gastrodin Decreases Hepatotoxicity via MAPK and Nrf2 Signaling Pathways

Chia-Chih Liao and Huang-Ping Yu were equal contributors and co-first authors.

The original online version of this article was revised: The originally published version of this article contained mistakes. The marks "*" and "#" were missing in Figures 3, 4, 5 and 6.

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Liao, CC., Yu, HP., Chou, AH. et al. Gastrodin Alleviates Acetaminophen-Induced Liver Injury in a Mouse Model Through Inhibiting MAPK and Enhancing Nrf2 Pathways. Inflammation 45, 1450–1462 (2022). https://doi.org/10.1007/s10753-021-01557-1

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