Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of th...

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Autores principales: Jun-Ming Wang, Jin-Yang Li, Hong Cai, Rong-Xing Chen, Yue-Yue Zhang, Lu-Lu Zhang, Ying Cui, Yong-Xian Cheng
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Publicado: Taylor & Francis Group 2019
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spelling oai:doaj.org-article:59684b64a4fe4e34963c854d31ac364a2021-11-17T14:21:56ZNrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology1388-02091744-511610.1080/13880209.2019.1634106https://doaj.org/article/59684b64a4fe4e34963c854d31ac364a2019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1634106https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 μg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 μg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 μg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 μg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.Jun-Ming WangJin-Yang LiHong CaiRong-Xing ChenYue-Yue ZhangLu-Lu ZhangYing CuiYong-Xian ChengTaylor & Francis Grouparticlelonicera japonica thunblysimachia christinae hanceglycyrrhiza uralensis fischpaeonia lactiflora pallphaseolus radiatus lTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 437-448 (2019)
institution DOAJ
collection DOAJ
language EN
topic lonicera japonica thunb
lysimachia christinae hance
glycyrrhiza uralensis fisch
paeonia lactiflora pall
phaseolus radiatus l
Therapeutics. Pharmacology
RM1-950
spellingShingle lonicera japonica thunb
lysimachia christinae hance
glycyrrhiza uralensis fisch
paeonia lactiflora pall
phaseolus radiatus l
Therapeutics. Pharmacology
RM1-950
Jun-Ming Wang
Jin-Yang Li
Hong Cai
Rong-Xing Chen
Yue-Yue Zhang
Lu-Lu Zhang
Ying Cui
Yong-Xian Cheng
Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology
description Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 μg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 μg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 μg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 μg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.
format article
author Jun-Ming Wang
Jin-Yang Li
Hong Cai
Rong-Xing Chen
Yue-Yue Zhang
Lu-Lu Zhang
Ying Cui
Yong-Xian Cheng
author_facet Jun-Ming Wang
Jin-Yang Li
Hong Cai
Rong-Xing Chen
Yue-Yue Zhang
Lu-Lu Zhang
Ying Cui
Yong-Xian Cheng
author_sort Jun-Ming Wang
title Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology
title_short Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology
title_full Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology
title_fullStr Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology
title_full_unstemmed Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology
title_sort nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of radix tripterygium wilfordii to s180-bearing mice by herbal-processing technology
publisher Taylor & Francis Group
publishDate 2019
url https://doaj.org/article/59684b64a4fe4e34963c854d31ac364a
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