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Toxicol In Vitro. 2019 Apr;56:141-149. doi: 10.1016/j.tiv.2019.01.016. Epub 2019 Jan 23.

Catalpol and panax notoginseng saponins synergistically alleviate triptolide-induced hepatotoxicity through Nrf2/ARE pathway.

Author information

1
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
2
Wuxi 9th People's Hospital & Wuxi 9th Affiliated Hospital of Soochow University, Wuxi 214062, PR China; Jiangsu Provincial Key Laboratory of Pharmacology and Safety Evaluation of Material Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
3
Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, PR China.
4
Jiangsu Provincial Key Laboratory of Pharmacology and Safety Evaluation of Material Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
5
Jiangsu Provincial Key Laboratory of Pharmacology and Safety Evaluation of Material Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China. Electronic address: llzhou74@163.com.
6
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, PR China. Electronic address: zxp_njucm@163.com.

Abstract

Triptolide (TP), as the main component of Tripterygium wilfordii (TW), could induce significant hepatic damage when exerting the therapeutic effect. However, The previous studies have shown that catalpol (CAT) and panax notoginseng saponins (PNS) have synergistic protecting effect against hepatotoxicity induced by TP. This study aims to address the role of the nuclear factor erythroid-2-related factor-2 (Nrf2)/antioxidant response element (ARE) pathway in their protecting effect, and to explore their synergistic mechanisms. For this purpose, the human hepatocyte cell line L-02 was selected, and the synergistic antioxidative effect of CAT and PNS was confirmed. Then the effects of CAT and PNS on different aspects of the Nrf2/ARE pathway were analyzed. The results showed that CAT significantly reduced TP-induced inhibition of Nrf2 transcription and made it increased, PNS significantly increased Nrf2 phosphorylation for relieving TP-induced potential inhibition of Nrf2/ARE binding activity, while the combination of the two further enhanced their activation by synergistically inducing Nrf2 transcriptional expression and phosphorylated Nrf2 (p-Nrf2) expression, followed with NAD(P)H:quinine oxidoreductase 1 (NQO1) expression and glutathione (GSH) activity increasing, which further enhanced their antioxidative effects. Subsequently, the gene silencing techniques were used, and that the Nrf2/ARE pathway is necessary in this effect was confirmed. In conclusion, the synergistic protecting effect of CAT and PNS is dependent on Nrf2/ARE pathway, while the natural mutual promotion between the regulatory links of CAT and PNS may be the main source of the synergistic effect.

KEYWORDS:

Catalpol; Hepatotoxicity; Nrf2; Oxidative stress; Panax notoginseng saponins; Triptolide

PMID:
30682494
DOI:
10.1016/j.tiv.2019.01.016
[Indexed for MEDLINE]

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