The molecular pathogenesis of triptolide-induced hepatotoxicity

Yeqing Hu; Qiguo Wu; Yulin Wang; Haibo Zhang; Xueying Liu; Hua Zhou; Tao Yang

doi:10.3389/fphar.2022.979307

The molecular pathogenesis of triptolide-induced hepatotoxicity

Front Pharmacol. 2022 Aug 24:13:979307. doi: 10.3389/fphar.2022.979307. eCollection 2022.

Authors

Yeqing Hu^{1

2

3}, Qiguo Wu⁴, Yulin Wang^{1

2

3}, Haibo Zhang^{1

2

3}, Xueying Liu^{1

2

3}, Hua Zhou^{1

2

3}, Tao Yang^{1

2

3

5}

Affiliations

¹ Institute of Cardiovascular Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shanghai, China.
⁴ Department of Pharmacy, Anqing Medical College, Anqing, China.
⁵ Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China.

Abstract

Triptolide (TP) is the major pharmacologically active ingredient and toxic component of Tripterygium wilfordii Hook. f. However, its clinical potential is limited by a narrow therapeutic window and multiple organ toxicity, especially hepatotoxicity. Furthermore, TP-induced hepatotoxicity shows significant inter-individual variability. Over the past few decades, research has been devoted to the study of TP-induced hepatotoxicity and its mechanism. In this review, we summarized the mechanism of TP-induced hepatotoxicity. Studies have demonstrated that TP-induced hepatotoxicity is associated with CYP450s, P-glycoprotein (P-gp), oxidative stress, excessive autophagy, apoptosis, metabolic disorders, immunity, and the gut microbiota. These new findings provide a comprehensive understanding of TP-induced hepatotoxicity and detoxification.

Keywords: CYP450s; hepatotoxicity; immunity; oxidative stress; triptolide.

Publication types

Review