Abstract
Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.
Highlights
There is a long history of using traditional Chinese medicine for the treatment of various diseases.It has been recorded that 943 species of toxic plants exist in China, of which more than 500 species are medicinal plants
As one process of cell death that is different from apoptosis, has attracted much attention
Studies have revealed that necrosis plays an important role in drug-induced liver injury [17]. of P. hookeri (PH)
Summary
There is a long history of using traditional Chinese medicine for the treatment of various diseases. It has been recorded that 943 species of toxic plants exist in China, of which more than 500 species are medicinal plants. 83 toxic traditional Chinese medicines are included in the Chinese. The severe side effects of toxic constituents from herbs, such as aristolochic acid [2], have aroused people’s widespread attention. It is urgent to evaluate toxicities, allowing for Toxins 2019, 11, 142; doi:10.3390/toxins11030142 www.mdpi.com/journal/toxins allowing for a more rational assessment of risks in the clinic application of these medicines. As the main organ of drug metabolism in the body, the liver is more likely to be a target organ damaged by drugs. Studies have shown that herbs were the second cause of drug-induced liver injury in the United
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