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

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.

Long-Chain Poly-d-Lysines Interact with the Plasma Membrane and Induce Protective Autophagy and Intense Cell Necrosis

“…As shown in Figure A, the mean fluorescence intensity (MFI) of PDL-treated A549 cells and HPAEpiCs was about 1.4 and 1.5 times higher than that of the PLL-treated A549 cells and HPAEpiCs, respectively, indicating that PDL has a more remarkable influence on the cell necrosis. We also measured the lactate dehydrogenase (LDH, a soluble cytoplasmic enzyme found in almost all cells, which is released into the extracellular region when the plasma membrane is damaged , ) content in the culture medium of A549 cells and HPAEpiCs treated with PLL or PDL for 2 h, and the results shown in Figure B revealed that PDL could induce a much stronger effect on the release of LDH, suggesting that the cell membrane integrity was compromised in the PDL-treated cells. The above results demonstrated that PDL could severely destroy the cell membrane, leading to the increase of intracellular Ca 2+ and LDH release, which are the features of cell necrosis.…”

Oxybaphus himalaicus Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation

“…RAW264.7 macrophages were seeded into 96-well plates at a density of 1 × 10 4 cells per well and cultured for 24 h. Then, cells were treated with different concentrations of fraction A-E isolated O. himalaicus and cultured for 24 h. Cell viability was detected by MTT assay according to our previous study [ 11 ].…”

Traditional uses, phytochemistry, pharmacology, and toxicology of Pterocephalus hookeri (C. B. Clarke) Höeck: a review

“…These results indicated that the extract can induce liver toxicity in vivo and in vitro , which can induce the development of inflammation and subsequent necrosis. 63 …”