Diagnosis, toxicological mechanism, and detoxification for hepatotoxicity induced by pyrrolizidine alkaloids from herbal medicines or other plants

Abstract

Pyrrolizidine alkaloids (PAs) are one type of phytotoxins distributed in various plants, including many medicinal herbs. Many organs might suffer injuries from the intake of PAs, and the liver is the most susceptible one. The diagnosis, toxicological mechanism, and detoxification of PAs-induced hepatotoxicity have been studied for several decades, which is of great significance for its prevention, diagnosis, and therapy. When the liver was exposed to PAs, liver sinusoidal endothelial cells (LSECs) loss, hemorrhage, liver parenchymal cells death, nodular regeneration, Kupffer cells activation, and fibrogenesis occurred. These pathological changes classified the PAs-induced liver injury as acute, sub-acute, and chronic type. PAs metabolic activation, mitochondria injury, glutathione (GSH) depletion, inflammation, and LSECs damage-induced activation of the coagulation system were well recognized to play critical roles in the pathological process of PAs-induced hepatotoxicity. A lot of natural compounds like glycyrrhizic acid, (-)-epicatechin, quercetin, baicalein, chlorogenic acid, and so on were demonstrated to be effective in alleviating PAs-induced liver injury, which rendered them huge potential to be developed into therapeutic drugs for PAs poisoning in clinics. This review presents updated information about the diagnosis, toxicological mechanism, and detoxification studies on PAs-induced hepatotoxicity.

Keywords:

• Pyrrolizidine alkaloids
• hepatotoxicity
• diagnosis
• toxicological mechanism
• detoxification

Acknowledgments

The authors would like to express their gratitude to the external reviewers who reviewed the original manuscript and gave them valuable comments, and to their colleagues, Prof. Wang Zhengtao and Prof. Wang Changhong from Shanghai University of Traditional Chinese Medicine, who reviewed the revised manuscript and gave them helpful suggestions. The authors would also like to thank BioReder.com for providing templates which is useful for the creation of Figures 2 and 3.

Declaration of interest

L. L. Ji conceptualized the elements of this article. Z. L. Huang, Z. Q. Wu and X. N. Gu did the literature review. Z. L. Huang wrote this manuscript and L. L. Ji revised it. The authors declare that they have no conflict of interests.

Additional information

Funding

This work was financially supported by “Young Qihuang Scholar” and Program of Shanghai Academic Research Leader (23XD1404000) for Lili Ji, National Natural Science Foundation of China (82104509), and the Shanghai Pujiang Program (22PJ1412900) for Zhenlin Huang.