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Antihepatotoxic Effect of Tadehaginoside, Extracted from Tadehagi triquetrum (L.), Against CCl4-Lesioned Rats Through Activating the Nrf2 Signaling Pathway and Attenuating the Inflammatory Response

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Abstract

Recently, an increasing number of studies suggest that oxidative stress and inflammation are associated with hepatocellular injuries. Thus, we aimed to evaluate the potential hepatoprotective role of tadehaginoside (TA) on liver lesions induced by carbon tetrachloride (CCl4). The results in vitro suggested that TA dose-dependently suppressed the cell proliferation of HepG2 cells, whereas the phosphorylated level of IκBα in cells was effectively inactivated. The study in vivo showed that TA significantly lowered the serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin E (IgE), and leukotriene (LT) in CCl4-lesioned rats. Pathological examination indicated that CCl4-induced hepatocellular damage was effectively mitigated by TA treatment. Meanwhile, the contents of γ-glutamylcysteine synthetase (γ-GCS), glutathione (GSH), and catalase (CAT) in liver tissue were gradually elevated. In addition, cytochrome c oxidase (COX) mRNA expression in hepatocytes was markedly upregulated, and nuclear factor E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keapl) levels were progressively increased. Furthermore, the tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B (NF-κB)-expressed protein were downregulated. These findings demonstrate that tadehaginoside effectively protects against CCl4-induced oxidative injury and inflammatory reaction in hepatocytes, in which the underlying mechanisms are involved in activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway, thereby attenuating oxidative stress and reducing the inflammation in liver cells.

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Acknowledgments

We are grateful to Mr. Jiaquan Li for his excellent technical support.

Conflict of Interest

The authors declare they have no conflicts of interest and are responsible for the contents of this report.

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Authors and Affiliations

  1. The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89 Dongge Road, Nanning City, Guangxi, 530023, People’s Republic of China

    Aicun Tang & Xiaoyan Wu

  2. Department of Clinical Pharmacy, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China

    Xiaoyu Chen

  3. Department of Pharmacy, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China

    Qiuyu Lu

  4. Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China

    Ni Zheng

  5. Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of China

    Yanfei Wei

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  1. Aicun Tang
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  4. Ni Zheng
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Correspondence to Xiaoyan Wu.

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Aicun Tang and Xiaoyu Chen contributed equally to this work.

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Tang, A., Chen, X., Lu, Q. et al. Antihepatotoxic Effect of Tadehaginoside, Extracted from Tadehagi triquetrum (L.), Against CCl4-Lesioned Rats Through Activating the Nrf2 Signaling Pathway and Attenuating the Inflammatory Response. Inflammation 37, 1006–1014 (2014). https://doi.org/10.1007/s10753-014-9821-5

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