Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

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 fromP. hookeriwas mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.Keywords:Pterocephalus hookeri;liver toxicity;n-butanol extract;necrosis;inflammationKey Contribution:(1)Pterocephalus hookericould induce liver toxicity in vivo and in vitro. (2) The liver toxicity was induced by n-butanol extract ofP. hookeri. (3) The liver toxicity was mainly caused by necrosis associated with inflammation. (4) This finding provides an important theoretical support for further evaluation of the safety of this Tibetan medicine.