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 i...
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MDPI AG
2019-03-01
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author | Rui Wang Zhaoyue Dong Xiaolong Zhang Jingxin Mao Fancheng Meng Xiaozhong Lan Zhihua Liao Min Chen |
author_facet | Rui Wang Zhaoyue Dong Xiaolong Zhang Jingxin Mao Fancheng Meng Xiaozhong Lan Zhihua Liao Min Chen |
author_sort | Rui Wang |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-e9a1f0716f0f4767806ad6bc3a24e1152022-12-22T04:28:24ZengMDPI AGToxins2072-66512019-03-0111314210.3390/toxins11030142toxins11030142Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering NecrosisRui Wang0Zhaoyue Dong1Xiaolong Zhang2Jingxin Mao3Fancheng Meng4Xiaozhong Lan5Zhihua Liao6Min Chen7College of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, Southwest University, Chongqing 400715, ChinaTAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, ChinaSchool of Life Sciences, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, Southwest University, Chongqing 400715, ChinaPterocephalus 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.http://www.mdpi.com/2072-6651/11/3/142Pterocephalus hookeriliver toxicityn-butanol extractnecrosisinflammation |
spellingShingle | Rui Wang Zhaoyue Dong Xiaolong Zhang Jingxin Mao Fancheng Meng Xiaozhong Lan Zhihua Liao Min Chen Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis Toxins Pterocephalus hookeri liver toxicity n-butanol extract necrosis inflammation |
title | Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis |
title_full | Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis |
title_fullStr | Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis |
title_full_unstemmed | Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis |
title_short | Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis |
title_sort | evaluation of the liver toxicity of pterocephalus hookeri extract via triggering necrosis |
topic | Pterocephalus hookeri liver toxicity n-butanol extract necrosis inflammation |
url | http://www.mdpi.com/2072-6651/11/3/142 |
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